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Referencias

References to studies included in this review

Amorim 1999 {published and unpublished data}

Amorim MM, Santos LC, Faundes A. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. American Journal of Obstetrics and Gynecology 1999;180(5):1283-8. CENTRAL

Attawattanakul 2015 {published data only}

Attawattanakul N, Tansupswatdikul P. Effects of antenatal dexamethasone on respiratory distress in late preterm infant: a randomized controlled trial. Thai Journal of Obstetrics and Gynaecology 2015;23:25-33. CENTRAL

Balci 2010 {published data only}

Balci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecologic and Obstetric Investigation 2010;70(2):95-9. CENTRAL

Block 1977 {published data only}

Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstetrics & Gynecology 1977;50:186-90. CENTRAL

Cararach 1991 {published data only}

Botet F, Cararach V, Sentis J. Premature rupture of membranes in early pregnancy. Neonatal prognosis. Journal of Perinatal Medicine 1994;22:45-52. CENTRAL
Cararach V, Botet F, Sentis J, Carmona F. A multicenter, prospective randomized study in premature rupture of membranes (PROM). Maternal and perinatal complications. International Journal of Gynecology and Obstetrics 1991;36 Suppl:267. CENTRAL
Cararach V, Sentis J, Botet F, De Los Rios L. A multicenter, prospective randomized study in premature rupture of membranes (PROM). Respiratory and infectious complications in the newborn. In: Proceedings of the 12th European Congress of Perinatal Medicine; 1990; Lyon, France. 1990:216. CENTRAL

Carlan 1991 {published data only}

Carlan SJ, Parsons M, O'Brien WF, Krammer J. Pharmacologic pulmonary maturation in preterm premature rupture of membranes. American Journal of Obstetrics and Gynecology 1991;164:371. CENTRAL

Collaborative 1981 {published data only}

Bauer CR, Morrison JC, Poole WK, Korones SB, Boehm JJ, Rigatto H, et al. A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy. Pediatrics 1984;73:682-8. CENTRAL
Burkett G, Bauer CR, Morrison JC, Curet LB. Effect of prenatal dexamethasone administration on the prevention of respiratory distress syndrome in twin pregnancies. Journal of Perinatology 1986;6:304-8. CENTRAL
Collaborative Group on Antenatal Steroid Therapy. Amniotic fluid phospholipids after maternal administration of dexamethasone. American Journal of Obstetrics and Gynecology 1983;145:484-90. CENTRAL
Collaborative Group on Antenatal Steroid Therapy. Effect of antenatal dexamethasone administration in the infant: long term follow-up. Journal of Pediatrics 1984;105:259-67. CENTRAL
Collaborative Group on Antenatal Steroid Therapy. Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1981;141:276-87. CENTRAL
Curet LB, Rao AV, Zachman RD, Morrison J, Burkett G, Poole K, et al. Maternal smoking and respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1983;147:446-50. CENTRAL
Haning RV, Curet LB, Poole K, Boehnlein LM, Kuzma DL, Meier SM. Effects of fetal sex and dexamethasone on preterm maternal serum concentrations of human chorionic gonadotropin, progesterone, estrone, estradiol, and estriol. American Journal of Obstetrics and Gynecology 1989;161:1549-53. CENTRAL
Wiebicke W, Poynter A, Chernick V. Normal lung growth following antenatal dexamethasone treatment for respiratory distress syndrome. Pediatric Pulmonology 1988;5:27-30. CENTRAL
Zachman RD, Bauer CR, Boehm J, Korones SB, Rigatto H, Rao AV. Effect of antenatal dexamethasone on neonatal leukocyte count. Journal of Perinatology 1988;8:111-3. CENTRAL
Zachman RD. The NIH multicenter study and miscellaneous clinical trials of antenatal corticosteroid administration. In: Farrell PM, editors(s). Lung Development: Biological and Clinical Perspectives. Vol. II. London & New York: Academic Press, 1982:275-96. CENTRAL

Dexiprom 1999 {published and unpublished data}

Pattinson RC, Funk M, Makin JD, Ficki H. The effect of dexamethasone on the immune system of women with preterm premature rupture of membranes: a randomised controlled trial. In: 15th Conference on Priorities in Perinatal Care in Southern Africa; 1996 March 5-8; Goudini Spa, South Africa. 1996. CENTRAL
Pattinson RC, Makin JD, Funk M, Delport SD, Macdonald AP, Norman K. The use of dexamethasone in women with preterm premature rupture of membranes: a multicentre double blind, placebo controlled randomised trial. South African Medical Journal 1999;89(8):865-70. CENTRAL
Pattinson RC. A meta-analysis of the use of corticosteroids in pregnancies complicated by preterm premature rupture of membranes. South African Medical Journal 1999;89(8):870-3. CENTRAL
The DEXIPROM Study Group. The use of dexamethasone in women with preterm premature rupture of membranes: a multicentre placebo controlled randomised controlled trial. In: 16th Conference on Priorities in Perinatal Care; 1997; South Africa. 1997:32-4. CENTRAL

Doran 1980 {published data only}

Doran TA, Swyer P, MacMurray B, Mahon W, Enhorning G, Bernstein A, et al. Results of a double blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1980;136:313-20. CENTRAL

Fekih 2002 {published data only}

Fekih M, Chaieb A, Sboui H, Denguezli W, Hidar S, Khairi H. Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study [Apport de la corticotherapie antenatale dans la prevention de la maladie des membranes hyalines chez le premature. Etude prospective randomisee]. Tunisie Medicale 2002;80(5):260-5. CENTRAL

Gamsu 1989 {published data only}

Donnai P. UK multicentre trial of betamethasone for the prevention of respiratory distress syndrome. In: Proceedings of the 6th European Congress of Perinatal Medicine; 1978 Aug 29-Sept 1; Vienna, Austria. 1978:Abstract no: 81. CENTRAL
Gamsu HR, Mullinger BM, Donnai P, Dash CH. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. British Journal of Obstetrics and Gynaecology 1989;96:401-10. CENTRAL

Garite 1992 {published data only}

Garite TJ, Rumney PJ, Briggs GG, Harding JA, Nageotte MP, Towers CV, et al. A randomized placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24-28 weeks gestation. American Journal of Obstetrics and Gynecology 1992;166:646-51. CENTRAL
Garite TJ, Rumney PJ, Briggs GG. A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24-28 weeks gestation. Surgery, Gynecology and Obstetrics 1993;176:37. CENTRAL

Goodner 1979 {published data only}

Goodner DM. Antenatal steroids in the treatment of respiratory distress syndrome. In: 9th World Congress of Gynecology and Obstetrics; 1979 October 26-31; Tokyo, Japan. 1979:362. CENTRAL

Gyamfi‐Bannerman 2016 {published data only}NCT01222247

Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. New England Journal of Medicine 2016;374(14):1311-20. CENTRAL
Gyamfi-Bannerman C. Antenatal late preterm steroids (ALPS): a randomized trial to reduce neonatal respiratory morbidity. American Journal of Obstetrics and Gynecology 2016;214(1 Suppl):S2. CENTRAL
NCT01222247. Antenatal late preterm steroids (ALPS): a randomized placebo-controlled trial. clinicaltrials.gov/ct2/show/NCT01222247 Date first received: 14 October 2010. CENTRAL

Kari 1994 {published data only}

Eronen M, Kari A, Pesonen E, Hallman M. The effect of antenatal dexamethasone administration on the fetal and neonatal ductus arteriosus: a randomised double-blind study. American Journal of Diseases of Children 1993;147:187-92. CENTRAL
Kari MA, Akino T, Hallman M. Prenatal dexamethasone (DEX) treatment before preterm delivery and rescue therapy of exogenous surfactant- surfactant components and surface activity in airway specimens (AS). In: Proceedings of the 14th European Congress of Perinatal Medicine; 1994 June 5-8; Helsinki, Finland. 1994:Abstract no: 486. CENTRAL
Kari MA, Hallman M, Eronen M, Teramo K, Virtanen M, Koivisto M, et al. Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomised placebo-controlled multicenter study. Pediatrics 1994;93:730-6. CENTRAL
Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, von Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta Paediatrica 1997;86:294-8. CENTRAL

Khazardoust 2012 {published data only}

Hantoushzadeh S, Javadian P, Salmanian B, Ghazanfari T, Kermani A, Abbasalizadeh F, et al. Betamethasone effects on the endocervical inflammatory cytokines in preterm labor: a randomized clinical trial. International Immunopharmacology 2011;11(8):1116-9. CENTRAL
Khazardoust S, Javadian P, Salmanian B, Zandevakil F, Abbasalizadeh F, Alimohamadi S, et al. A clinical randomized trial on endocervical inflammatory cytokines and Betamethasone in prime-gravid pregnant women at risk of preterm labor. Iranian Journal of Immunology 2012;9(3):199-207. CENTRAL

Lewis 1996 {published data only}

Lewis D, Brody K, Edwards M, Brouillette RM, Burlison S, London SN. Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics. Obstetrics & Gynecology 1996;88(5):801-5. CENTRAL

Liggins 1972b {published and unpublished data}

Dalziel SR, Fenwick S, Cundy T, Parag V, Beck TJ, Rodgers A, et al. Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial. Journal of Bone & Mineral Research 2006;21(8):1175-86. CENTRAL
Dalziel SR, Liang A, Parag V, Rodgers A, Harding JE. Blood pressure at 6 years of age after prenatal exposure to betamethasone: follow-up results of a randomized, controlled trial. Pediatrics 2004;114:e373-e377. CENTRAL
Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 2005;331:665. CENTRAL
Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Psychological functioning and health-related quality of life in adulthood after preterm birth. Developmental Medicine and Child Neurology 2007;49(8):597-602. CENTRAL
Dalziel SR, Parag V, Harding JE. Blood pressure at 6 years of age following exposure to antenatal betamethasone. In: 7th Annual Congress of the Perinatal Society of Australia and New Zealand; 2003 March 9-12; Tasmania, Australia. 2003:P13. CENTRAL
Dalziel SR, Rea HH, Walker NK, Parag V, Mantell C, Rodgers A, et al. Long term effects of antenatal betamethasone on lung function: 30 year follow up of a randomised controlled trial. Thorax 2006;61(8):678-83. CENTRAL
Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A, et al. Cardiovascular risk factors after exposure to antenatal betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005;365:1856-62. CENTRAL
Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A, et al. Long-term effects of antenatal exposure to betamethasone: thirty year follow-up of a randomised controlled trial [abstract]. Pediatric Research 2004;55 Suppl:101. CENTRAL
Dalziel SR, Walker NR, Parag V, Mantell C, Rea HH, Rodgers A, et al. Long-term effects of antenatal exposure to betamethasone: thirty year follow-up of a randomized controlled trial. In: Pediatric Academic Societies Annual Meeting; 2004 May 1-4; San Francisco, USA. 2004. CENTRAL
Harding JE, Pang J, Knight DB, Liggins GC. Do antenatal corticosteroids help in the setting of preterm rupture of membranes? American Journal of Obstetrics and Gynecology 2001;184:131-9. CENTRAL
Howie RN, Liggins GC. Clinical trial of antepartum betamethasone therapy for prevention of respiratory distress in pre-term infants. In: Anderson ABM, Beard RW, Brudenell JM, Dunn PM, editors(s). Pre-term Labour. London: RCOG, 1977:281-9. CENTRAL
Howie RN, Liggins GC. Prevention of respiratory distress syndrome in premature infants by antepartum glucocorticoid treatment. In: Villee CA, Villee DB, Zuckerman J, editors(s). Respiratory Distress Syndrome. London & New York: Academic Press, 1973:369-80. CENTRAL
Howie RN, Liggins GC. The New Zealand study of antepartum glucocorticoid treatment. In: Farrell PM, editors(s). Lung Development: Biological and Clinical Perspectives, II. Academic Press: London & New York, 1982:255-65. CENTRAL
Howie RN. Pharmacological acceleration of lung maturation. In: Villee CA, Villee DB, Zuckerman J, editors(s). Respiratory Distress Syndrome. London & New York: Academic Press, 1986:385-96. CENTRAL
Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515-25. CENTRAL
Liggins GC, Howie RN. Prevention of respiratory distress syndrome by antepartum corticosteroid therapy. In: Proceedings of Sir Joseph Barcroft Centenary Symposium, Fetal and Neonatal Physiology; 1972; UK. Cambridge University Press: UK, 1973:613-7. CENTRAL
Liggins GC, Howie RN. Prevention of respiratory distress syndrome by maternal steroid therapy. In: Gluck L, editors(s). Modern Perinatal Medicine. Chicago: Yearbook Publishers, 1974:415-24. CENTRAL
Liggins GC. Prenatal glucocorticoid treatment: prevention of respiratory distress syndrome. In: Moore TD , editors(s). Lung maturation and the prevention of hyaline membrane disease, report of 70th Ross Conference on Paediatric Research. Ross Labs, 1976:97-103. CENTRAL
MacArthur B, Howie RN, DeZoete A, Elkins J, Liang AYL. Long term follow up of children exposed to betamethasone in utero. In: Tejani N, editors(s). Obstetrical Events and Developmental Sequelae. CRC Press, 1989:81-9. CENTRAL
MacArthur B, Howie RN, DeZoete A, Elkins J. Cognitive and psychosocial development of 4-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 1981;68:638-43. CENTRAL
MacArthur B, Howie RN, DeZoete A, Elkins J. School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 1982;70:99-105. CENTRAL

Lopez 1989 {published data only}

Lopez ALV, Rojas RL, Rodriguez MV, Sanchez AJ. Use of corticoids in preterm pregnancy with premature rupture of membranes [Uso de los corticoides en embarazo pretermino con ruptura prematura de membranas]. Revista Colombiana de Obstetricia y Ginecologia 1989;40:147-51. CENTRAL

Mansouri 2010 {published data only}

IRCT138901193666N1. Effect of antenatal betamethasone on prevention of respiratory distress syndrome among neonates with gestational age of 35-36 weeks. www.irct.ir Date first received: 17 May 2010. CENTRAL
Mansouri M, Seyedolshohadaei F, Company F, Setare S, Mazhari S. Effect of antenatal betamethasone on prevention of respiratory distress syndrome among neonates with gestational age of 35-36 weeks. Journal of Gorgan University of Medical Sciences 2010;12(3):18-23. CENTRAL

Morales 1989 {published data only}

Morales WJ, Angel JL, O'Brien WF, Knuppel RA. Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. Obstetrics & Gynecology 1989;73:721-6. CENTRAL

Nelson 1985 {published data only}

Nelson LH, Meis PJ, Hatjis CG, Ernest JM, Dillard R, Schey HM. Premature rupture of membranes: a prospective randomized evaluation of steroids, latent phase and expectant management. Obstetrics & Gynecology 1985;66:55-8. CENTRAL

Parsons 1988 {published data only}

Parsons MT, Sobel D, Cummiskey K, Constantine L, Roitman J. Steroid, antibiotic and tocolytic vs no steroid, antibiotic and tocolytic management in patients with preterm PROM at 25-32 weeks. In: Proceedings of the 8th Annual Meeting of the Society of Perinatal Obstetricians; 1988 Feb 3-6; Las Vegas, Nevada. 1988:44. CENTRAL
Sobel D, Parsons M, Roitman J, McAlpine L, Cumminsky K. Antenatal antibiotics in PROM prevents congenital bacterial infection. Pediatric Research 1988;23:476A. CENTRAL

Porto 2011 {published data only}

Porto AMF, Coutinho IC, Correia JB, Amorim MMR. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011;342:d1696. CENTRAL

Qublan 2001 {published data only}

Qublan H, Malkawi H, Hiasat M, Hindawi IM, Al-Taani MI, Abu-Khait SA, et al. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. Clinical & Experimental Obstetrics & Gynecology 2001;28(3):183-6. CENTRAL

Schutte 1980 {published data only}

Dessens AB, Haas HS, Koppe JG. Twenty year follow up of antenatal corticosteroid treatment. Pediatrics 2000;105(6):1325. CENTRAL
Dessens AB, Smolders-de Haas H, Koppe JG. Twenty year follow up in antenatally corticosteroid-treated subjects. Prenatal and Neonatal Medicine 1998;3 Suppl 1:32. CENTRAL
Schmand B, Neuvel J, Smolder-de Haas H, Hoeks J, Treffers PE, Koppe JG. Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 1990;86:58-64. CENTRAL
Schutte MF, Koppe JG, Treffers PE, Breur W. The influence of 'treatment' in premature delivery on incidence of RDS. In: Proceedings of the 6th European Congress of Perinatal Medicine; 1978 Aug 29-Sept 1; Vienna, Austria. 1978:Abstract no: 80. CENTRAL
Schutte MF, Treffers PE, Koppe JG, Breur W, Filedt Kok JC. The clinical use of corticosteroids for the acceleration of fetal lung maturity [Klinische toepassing van corticosteroiden ter bevordering van de foetale long-rijpheid]. Nederlands Tijdschrift voor Geneeskunde 1979;123:420-7. CENTRAL
Schutte MF, Treffers PE, Koppe JG, Breur W. The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour. British Journal of Obstetrics and Gynaecology 1980;87:127-31. CENTRAL
Smolders-de Haas H, Neuvel J, Schmand B, Treffers PE, Koppe JG, Hoeks J. Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12- year follow up. Pediatrics 1990;86(1):65-70. CENTRAL

Shanks 2010 {published data only}

Shanks A, Gross G, Shim T, Allsworth J, Moga C, Sadovsky Y, et al. Antenatal steroids for enhancement of fetal lung maturity after 34 weeks: lung maturity and antenatal steroids (LUMAS) study. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S58. CENTRAL
Shanks A, Gross G, Shim T, Allsworth J, Sadovsky Y, Bildirici I. Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles. American Journal of Obstetrics and Gynecology 2010;203(1):47.e1-47.e5. CENTRAL

Silver 1996 {published data only}

Silver RK, Vyskocil CR, Solomon SL, Farrell EE, MacGregor SN, Neerhof MG. Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered prior to 30 weeks of gestation. American Journal of Obstetrics and Gynecology 1995;172:254. CENTRAL
Silver RK, Vyskocil CR, Solomon SL, Ragin A, Neerhof MG, Farrell EE. Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered prior to 30 weeks of gestation. Obstetrics & Gynecology 1996;87:683-91. CENTRAL

Taeusch 1979 {published data only}

Taeusch HW Jr, Frigoletto F, Kitzmiller J, Avery ME, Hehre A, Fromm B, et al. Risk of respiratory distress syndrome after prenatal dexamethasone treatment. Pediatrics 1979;63:64-72. CENTRAL

Teramo 1980 {published data only}

Teramo K, Hallman M, Raivio KO. Maternal glucocorticoid in unplanned premature labor. Pediatric Research 1980;14:326-9. CENTRAL

References to studies excluded from this review

Abuhamad 1999 {published data only}

Abuhamad A, Green G, Heyl P, de Veciana M. The combined use of corticosteroids and thyrotropin releasing hormone in pregnancies with preterm rupture of membranes: a randomised double blind controlled trial. American Journal of Obstetrics and Gynecology 1999;180(1 Pt 2):S96. CENTRAL

Althabe 2015 {published data only}NCT01084096

Althabe F, Belizan JM, Mazzoni A, Berrueta M, Hemingway-Foday J, Koso-Thomas M, et al. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol. Reproductive Health 2012;9(1):22. CENTRAL
Althabe F, Belizan JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet 2014;385(9968):629-639. CENTRAL [PMID: 25458726]

Asnafei 2004 {published data only}

Asnafei N, Pourreza R, Miri SM. Pregnancy outcome in premature delivery of between 34-37 weeks and the effects of corticosteroid on it. Journal of the Gorgan University of Medical Sciences 2004;6(2):57-60. CENTRAL

Butterfill 1979 {published data only}

Butterfill AM, Harvey DR. Follow-up study of babies exposed to betamethasone before birth. Archives of Disease in Childhood 1979;54:725. CENTRAL

Dola 1997 {published data only}

Dola C, Nageotte M, Rumney P, Towers C, Asrat T, Freeman R, et al. The effect of antenatal treatment with betamethasone and thyrotropin releasing hormone in patients with preterm premature rupture of membranes. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S49. CENTRAL

Egerman 1998 {published data only}

Egerman RS, Mercer B, Doss JL, Sibai BM. A randomized controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S19. CENTRAL
Egerman RS, Mercer BM, Doss JL, Sibai BM. A randomized, controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1998;179(5):1120-3. CENTRAL
Egerman RS, Pierce WF 4th, Andersen RN, Umstot ES, Carr TL, Sibai BM. A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy. Obstetrics & Gynecology 1997;89(2):276-80. CENTRAL
Egerman RS, Walker RA, Doss JL, Mercer B, Sibai BM, Andersen RN. A comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S182. CENTRAL
Egerman RS, Walker RA, Mercer BM, Doss JL, Sibai BM, Andersen RA. Comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester. American Journal of Obstetrics and Gynecology 1998;179(5):1234-6. CENTRAL

Garite 1981 {published data only}

Garite TJ, Freeman RK, Linzey EM, Braly PS, Dorchester WL. Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation. American Journal of Obstetrics and Gynecology 1981;141:508-15. CENTRAL

Grgic 2003 {published data only}

Grgic G, Fatusic Z, Bogdanovic G. Stimulation of fetal lung maturation with dexamethasone in unexpected premature labor. Medicinski Arhiv 2003;57(5-6):291-4. CENTRAL

Halac 1990 {published data only}

Halac E, Halac J, Begue EF, Casanas JM, Idiveri DR, Petit JF, et al. Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. Journal of Pediatrics 1990;117:132-8. CENTRAL

Iams 1985 {published data only}

Iams JD, Talbert ML, Barrows H, Sachs L. Management of preterm prematurely ruptured membranes: a prospective randomized comparison of observation vs use of steroids and timed delivery. American Journal of Obstetrics and Gynecology 1985;151:32-8. CENTRAL

Khandelwal 2012 {published data only}

Khandelwal M, Chang E, Hansen C, Hunter K, Milcarek B. Betamethasone dosing interval -12 or 24 hours apart? American Journal of Obstetrics and Gynecology 2012;206(Suppl 1):S10-S11. CENTRAL
Khandelwal M, Chang E, Hansen C, Hunter K, Milcarek B. Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial. American Journal of Obstetrics & Gynecology 2012;206(3):201.e1-11. CENTRAL

Koivisto 2007 {published data only}

Koivisto M, Peltoniemi OM, Saarela T, Tammela O, Jouppila P, Hallman M. Blood glucose level in preterm infants after antenatal exposure to glucocorticoid. Acta Paediatrica 2007;96(5):664-8. CENTRAL

Kuhn 1982 {published data only}

Kuhn RJP, Speirs AL, Pepperell RJ, Eggers TR, Doyle LW, Hutchinson A. Betamethasone, albuterol and threatened premature delivery. Obstetrics & Gynecology 1982;60:403-8. CENTRAL

Kurtzman 2008 {published data only}

Kurtzman J, Garite T, Clark R, Maurel K, The OCRN. Impact of a 'rescue course' of antenatal corticosteroids (ACS): a multi-center randomized placebo controlled trial. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S2. CENTRAL

Liu 2006 {published data only}

Liu J, Wang Q, Zhao JH, Chen YH, Qin GL. The combined antenatal corticosteroids and vitamin K therapy for preventing periventricular-intraventricular hemorrhage in premature newborns less than 35 weeks gestation. Journal of Tropical Pediatrics 2006;52(5):355-9. CENTRAL

Magee 1997 {published data only}

Magee LA, Dawes GS, Moulden M, Redman CW. A randomised controlled comparison of betamethasone with dexamethasone: effects on the antenatal fetal heart rate. British Journal of Obstetrics and Gynaecology 1997;104(11):1233-8. CENTRAL

Maksic 2008 {published data only}

Maksic H, Hadzagic-Catibusic F, Heljic S, Dizdarevic J. The effects of antenatal corticosteroid treatment on IVH-PVH of premature infants. Bosnian Journal of Basic Medical Sciences 2008;8(1):58-62. CENTRAL

McEvoy 2010 {published data only}

McEvoy C, Schilling D, Clay N, Spitale P, Durand M. Neurodevelopmental outcome and growth in infants randomized to a single rescue course of antenatal steroids. In: Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; 2011 April 30-May 3; Denver, Colorado, USA. 2011:3829.270. CENTRAL
McEvoy C, Schilling D, Peters D, Tillotson C, Spitale P, Wallen L, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. American Journal of Obstetrics and Gynecology 2010;202(6):544.e1-9. CENTRAL
McEvoy C, Schilling D, Segel S, Spitale P, Wallen L, Bowling S, et al. Improved respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized trial. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S228. CENTRAL
McEvoy C, Schilling D, Spitale P, Gravett M, Durand M. Pulmonary function and respiratory outcomes at 12-24 months in preterm infants randomized to a single rescue course of antenatal steroids. In: Pediatric Academic Societies' 2010 Annual Meeting; 2010 May 1-4; Vancouver, Canada. 2010. CENTRAL
McEvoy C, Schilling D, Spitale P, Wallen L, Segel S, Bowling S, et al. Improved respiratory compliance after a single rescue course of antenatal steroids: a randomized controlled trial. In: Pediatric Academic Societies Annual Meeting; 2008 May 2-6; Honolulu, Hawaii. 2008. CENTRAL
McEvoy C, Schilling D, Spitale P, Wallen L, Segel S, Bowling S, et al. Improved respiratory compliance after a single rescue course of antenatal steroids: a randomized controlled trial. Pediatric Academic Societies Annual Meeting; 2007 May 5-8; Toronto, Canada2007. CENTRAL
McEvoy C, Schilling D, Spitale P, Wallen P, Segel S, Bowling S, et al. Growth and respiratory outcomes after a single rescue course of antenatal steroids: a randomized trial. In: Pediatric Academic Societies Annual Meeting; 2009 May 2-5; Baltimore, USA. 2009. CENTRAL
McEvoy CT, Schilling D, Segal S, Spitale P, Wallen L, Bowling S, et al. Improved respiratory compliance in preterm infants <34 weeks after a single rescue course of antenatal steroids. American Journal of Respiratory and Critical Care Medicine 2009;179:A4127 [Poster #423]. CENTRAL

Minoui 1998 {published data only}

Minoui S, Ville Y, Senat M, Multon O, Fernandez H, Frydman R. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomized study. British Journal of Obstetrics and Gynaecology 1998;105:749-55. CENTRAL
Minoui S, Ville Y, Senat MV, Multon O, Fernandez H, Frydman R. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labor a randomized study. Prenatal and Neonatal Medicine 1996;1 Suppl 1:156. CENTRAL

Morales 1986 {published data only}

Morales WJ, Diebel D, Lazar AJ, Zadrozny D. The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with premature rupture of membranes. American Journal of Obstetrics and Gynecology 1986;154:591-5. CENTRAL

Morrison 1978 {published data only}

Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET. Effect of corticosteroids and fetomaternal disorders on the L:S ratio. Obstetrics & Gynecology 1980;56:583-90. CENTRAL
Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET. Effect of corticosteroids and fetomaternal disorders on the L:S ratio. Surgery, Gynecology and Obstetrics 1981;153:464. CENTRAL
Morrison JC, Whybrew WD, Bucovaz ET, Scheiner JM. Injection of corticosteroids into mother to prevent neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1978;131:358-66. CENTRAL

Mulder 1997 {published data only}

Mulder EJ, Derks JB, Visser GH. Antenatal corticosteroid therapy and fetal behaviour: a randomised evaluation of betamethasone and dexamethasone. British Journal of Obstetrics and Gynaecology 1997;104(11):1239-47. CENTRAL

Papageorgiou 1979 {published data only}

Papageorgiou AN, Desgranges MF, Masson M, Colle E, Shatz R, Gelfand MM. The antenatal use of betamethasone in the prevention of respiratory distress syndrome: a controlled blind study. Pediatrics 1979;63:73-9. CENTRAL

Romejko‐Wolniewicz 2013 {published data only}

Romejko-Wolniewicz E, Oleszczuk L, Zareba-Szczudlik J, Czajkowski K. Dosage regimen of antenatal steroids prior to preterm delivery and effects on maternal and neonatal outcomes. Journal of Maternal-Fetal and Neonatal Medicine 2013;26(3):237-41. CENTRAL

Rotmensch 1999 {published data only}

Rotmensch S, Liberati M, Vishne T, Celentano C, Ben-Rafael Z, Bellati U. The effects of betamethasone versus dexamethasone on computer-analysed fetal heart rate characteristics: a prospective randomized trial. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S185. CENTRAL
Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U. The effect of betamethasone and dexamethasone on the fetal heart rate patterns and biophysical activities. A prospective randomized trial. Acta Obstetricia et Gynecologica Scandinavica 1999;78(6):493-500. CENTRAL

Schmidt 1984 {published data only}

Schmidt PL, Sims ME, Strassner HT, Paul RH, Mueller E, McCart D. Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal infection. American Journal of Obstetrics and Gynecology 1984;148:178-86. CENTRAL

Simpson 1985 {published data only}

Simpson G, Harbert G. Use of beta-methasone in management of preterm gestation with premature rupture of membranes. Obstetrics & Gynecology 1985;66:168-75. CENTRAL

Whitt 1976 {published data only}

Whitt GG, Buster JE, Killam AP, Scragg WH. A comparison of two glucocorticoid regimens for acceleration of fetal lung maturation in premature labor. American Journal of Obstetrics and Gynecology 1976;124:479-82. CENTRAL

Althabe 2014

Althabe F, Belizan J, McClure E, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster- randomised trial. The Lancet 2014;385(9968):629-39. [DOI: 10.1016/S0140-6736(14)61651-2]

Amiya 2016

Amiya RM, Mlunde LB, Ota E, Swa T, Oladapo O, Mori R. Antenatal corticosteroids for reducing adverse maternal and child outcomes in special populations of women at risk of imminent preterm birth: a systematic review and meta-analysis. PLoS One 2016;11(2):e0147604. [DOI: 10.1371/journal.pone.0147604]

Antenatal Corticosteroid CPG Panel 2015

Antenatal Corticosteroids Clinical Practice Guidelines Panel. Antenatal corticosteroids given to women prior to birth to improve fetal, infant, child and adult health: Clinical Practice Guidelines. Liggins Institute, The University of Auckland, Auckland, New Zealand2015.

Azad 2014

Azad K, Costello A. Extreme caution is needed before scale-up of antenatal corticosteroids to reduce preterm deaths in low-income settings. Lancet 2014;2:e191-e192. [DOI: 10.1016/S2214-109X(14)70020-8]

Barker 1998

Barker DJP. Mothers, Babies and Health in Later Life. 2nd edition. London: Churchill Livingstone, 1998.

Benediktsson 1993

Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR. Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 1993;341(8841):339-41.

Brownfoot 2013

Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No: CD006764. [DOI: 10.1002/14651858.CD006764.pub3]

Clark 1998

Clark PM. Programming of the hypothalamo-pituitary-adrenal axis and the fetal origins of adult disease hypothesis. European Journal of Pediatrics 1998;157(1 Suppl):S7-S10.

Crowley 1990

Crowley P, Chalmers I, Keirse MJNC. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials. British Journal of Obstetrics and Gynaecology 1990;97:11-25.

Crowther 2015

Crowther CA, McKinlay CJD, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No: CD003935. [DOI: 10.1002/14651858.CD003935.pub4]

Deeks 2011

Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Dodic 1999

Dodic M, Wintour EM, Whitworth JA, Coghlan JP. Effect of steroid hormones on blood pressure. Clinical & Experimental Pharmacology & Physiology 1999;26(7):550-2.

Doyle 2001a

Doyle LW. Victorian Infant Collaborative Study Group. Outcome at 5 years of age of children 23 to 27 weeks' gestation: refining the prognosis. Pediatrics 2001;108(1):134-41.

Doyle 2001b

Doyle LW, Casalaz D. Victorian Infant Collaborative Study Group. Outcome at 14 years of extremely low birthweight infants: a regional study. Archives of Diseases in Childhood: Fetal and Neonatal Edition 2001;85(3):F159-F164.

Edwards 2001

Edwards LJ, Coulter CL, Symonds ME, McMillen IC. Prenatal undernutrition, glucocorticoids and the programming of adult hypertension. Clinical & Experimental Pharmacology & Physiology 2001;28(11):938-41.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.

Higgins 2011a

Higgins JPT, Deeks JJ (editors). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Higgins 2011b

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Hintz 2007

Hintz SR, Van Meurs KP, Perritt R, Poole WK, Das A, Stevenson DK, et al. Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide. Journal of Pediatrics 2007;151:e1-3.

Hofmeyr 2009

Hofmeyr GJ. Antenatal Corticosteroids For Women At Risk Of Preterm Birth. Geneva: The WHO Reproductive Health Library, World Health Organization, 2 February 2009. [http://apps.who.int/rhl/pregnancy_childbirth/complications/preterm_birth/cd004454_hofmeyrgj_com/en/]

Huang 1999

Huang WL, Beazley LD, Quinlivan JA, Evans SF, Nenham JP, Dunlop SA. Effect of corticosteroids on brain growth in fetal sheep. Obstetrics & Gynecology 1999;94(2):213-8.

Imseis 1996

Imseis HM, Iams JD. Glucocorticoid use in patients with preterm premature rupture of fetal membranes. Seminars in Perinatology 1996;20(5):439-50.

Jobe 1998

Jobe AH, Wada N, Berry LM, Ikegami M, Ervin MG. Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep. American Journal of Obstetrics and Gynecology 1998;178(5):880-5.

Liggins 1969

Liggins GC. Premature delivery of foetal lambs infused with corticosteroids. Journal of Endocrinology 1969;45:515-23.

Liggins 1972a

Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50(4):515-25.

Liggins 1976

Liggins GC. Prenatal glucocorticoid treatment: prevention of respiratory distress syndrome. In: Moore TD , editors(s). Lung maturation and the prevention of hyaline membrane disease, Report of the Seventieth Ross Conference on Pediatric Research, Columbus, Ohio. 1976:97-103.

NIH 1994

National Institutes of Health (NIH) Consensus Development Conference Statement. Effect of corticosteroids for fetal maturation on perinatal outcomes. American Journal of Obstetrics and Gynecology 1994;173:246-52.

Padbury 1996

Padbury JF, Ervin MG, Polk DH. Extrapulmonary effects of antenatally administered steroids. Journal of Pediatrics 1996;128(2):167-72.

RevMan 2014 [Computer program]

The Nordic Cochrane Centre, The Cochrane CollaborationReview Manager 5 (RevMan 5). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Rodriguez 2002

Rodriguez RJ, Martin RJ, Fanaroff, AA. Respiratory distress syndrome and its management. In: Fanaroff AA and Martin RJ, editors(s). Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. St. Louis: Mosby, 2002:1001-1010.

Schwab 2000

Schwab M, Roedel M, Akhtar Anwar M, Muler T, Schubert H, Buchwalder LF, et al. Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow. Journal of Physiology 2000;528(3):619-32.

Seckl 2000

Seckl JR, Cleasby M, Nyirenda MJ. Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming. Kidney International 2000;57(4):1412-7.

Sotiriadis 2009

Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JPA. Corticosteroids for preventing neonatal respiratory morbidity after elective caesarean section at term. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No: CD006614. [DOI: 10.1002/14651858.CD006614.pub2]

Sterne 2011

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Turrentine 1996

Turrentine MA, Wilson PD, Wilkins IA. A retrospective analysis of the effect of antenatal steroid on the incidence of respiratory distress syndrome in preterm twin pregnancies. American Journal of Perinatology 1996;13(6):351-4.

Vyas 1997

Vyas J, Kotecha S. Effects of antenatal and postnatal corticosteroids on the preterm lung. Archives of Disease in Childhood: Fetal and Neonatal Edition 1997;77(2):F147-F150.

Wellcome 2005

Reynolds LA, Tansey EM. Prenatal corticosteroids for reducing morbidity and mortality after preterm birth. The transcript of a Witness Seminar; The Wellcome Trust Centre for History of Medicine at UCL, London2005;25.

References to other published versions of this review

Crowley 2006

Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No: CD000065. [DOI: 10.1002/14651858.CD000065.pub2]

Roberts 2006

Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No: CD004454. [DOI: 10.1002/14651858.CD004454.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Amorim 1999

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: computer‐generated randomisation sequence with randomisation code kept by the chief pharmacist. The pharmacy provided coded drug boxes.
Stratification: none stated
Placebo: yes, same volume of similar appearing vehicle
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 2 (1%) women in the placebo group dropped out after randomisation
Funding: Instituto Materno‐Infantil de Pernambuco, Brazil

Participants

Location: Instituto Materno‐Infantil de Pernambuco, Recife, state of Pernambuco, Brazil
Timeframe: April 1997‐June 1998
Eligibility criteria: women with severe pre‐eclampsia, singleton pregnancy with a live fetus and gestational age between 26‐34 weeks. Likely minimal interval of 24 h between drug administration and delivery. Lung immaturity was confirmed by the foam test in fetuses of 30‐34 weeks. Gestational age range: 26‐34 weeks
Exclusion criteria: indication for immediate delivery, diabetes, PROM, maternal disease, congenital malformations, perinatal haemolytic disease, Group B streptococcal infection
Total recruited: 220 women and infants. 110 women and infants in each arm

Interventions

12 mg betamethasone IM, repeated after 24 h and weekly thereafter if delivery had not occurred.
Control group received identical placebo. Delivery was at 34 weeks or in the presence of maternal or fetal compromise in both groups.

Outcomes

Maternal outcomes (death, chorioamnionitis, maternal infection, fever after trial entry requiring antibiotics, intrapartum fever requiring antibiotics, postnatal fever, admission to ICU, glucose intolerance, hypertension), fetal/neonatal outcomes (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, Apgar score < 7, interval between trial entry and delivery, small‐for‐gestational age, admission to NICU, need for mechanical ventilation/CPAP, duration of oxygen supplementation, surfactant use, systemic infection in the first 48 h of life, proven infection while in the NICU, necrotising enterocolitis), childhood outcomes (death, developmental delay, cerebral palsy) and health service outcomes reported (length of antenatal hospitalisation for women, length of postnatal hospitalisation for women, length of neonatal hospitalisation)

Notes

Further information obtained from the study authors, including substantial unpublished data

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Computer‐generated randomisation sequence."

Allocation concealment (selection bias)

Low risk

"Randomisation code kept by the chief pharmacist."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants and investigators were blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome assessors was not described, but it is likely as the authors state, "the data analysis was carried out without knowledge of which of the treatments corresponded to corticosteroid and which to placebo". The code was fully broken only after the analysis was completed.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 women (1%) in the placebo group voluntarily dropped out after randomisation.

Selective reporting (reporting bias)

Low risk

Study protocol was not available, but study appears to report on all pre‐specified outcomes

Other bias

Low risk

The groups were comparable at baseline. The study appears free of other sources of bias.

Attawattanakul 2015

Study characteristics

Methods

Type of study: open label RCT
Method of treatment allocation: method of randomisation not stated. Block randomisation used

Stratification: none stated
Placebo: no, comparison was no treatment
Sample size calculation: "Sample size was calculated to have type one error of 5 percent and 80 percent power to detect a reduction of 50 percent in rate of respiratory distress. Rate of respiratory distress in late preterm infant was assumed to be 28.9 percent based on Wang ML, et al. Accordingly, the number of study population was at least 95 pregnant women in each group."
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated, though authors declare no competing interests

Participants

Location: Chonburi Hospital, Thailand
Timeframe: March 2013‐March 2014
Eligibility criteria: all pregnant women with singleton pregnancy admitted in labour (defined as "regular uterine contraction at least 4 times in 20 minutes or 8 times in 60 minutes and cervical dilatation more than 1 cm and cervical effacement at least 80 percent") with a gestational age of 34 weeks + 0 d to 36 weeks + 6 d

Gestational age range: 34 weeks + 0 d‐36 weeks + 6 d
Exclusion criteria: "Participants who had history of corticosteroid administration in current pregnancy, history of dexamethasone allergy, systemic infection, multifetal pregnancy, complicated pregnancy including overt diabetes mellitus, gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH), placenta previa and abruptio placentae, positive or unknown sexual transmitted disease serology, PROM, evidence of fetal amniotic membrane leakage confirmed by two of the following test; pooling, nitrazine test, fern test or cough test, known fetal intrauterine restriction, oligohydramnios, non‐reassuring fetal heart rate tracing, fetal death, fetal anomaly, suspicious of chorioamnionitis (fetal tachycardia >160/min, maternal fever > 37.8°C, uterine tenderness, foul smelling amniotic fluid), cervical dilatation more than 7 cm, were excluded from our study."
Total recruited: 194 women and infants; 96 women and infants in the treatment arm and 98 women and infants in the control arm.

Interventions

The treatment group received 6 mg dexamethasone IM, up to 4 doses 12 h apart.

The control group received no treatment.

Outcomes

Maternal outcomes (chorioamnionitis, side effects of therapy in women)

Fetal/neonatal outcomes (RDS, IVH, birthweight, necrotising enterocolitis, systemic infection in the first 48 h of life, need for mechanical ventilation/CPAP, Apgar score < 7, admission to NICU)

Notes

Labour augmentation performed if needed even if women had not received full course of steroids.

6 (6%) women in the intervention group received a full course of steroids; most women (75/96 (78%)) in the intervention arm received just 1 dose of dexamethasone.

Data for 'maternal local or systemic adverse reactions to treatment' have been included in the review under our outcome of maternal side effects.

Data from the trial are available for the following outcomes: low birthweight (not defined); hypoglycaemia in infant; need for respiratory support in infant (6/96 treatment and 14/98 control; (these data are in addition to the need for 'positive pressure ventilation' included in the review outcome 'need for mechanical ventilation'); and maternal length of stay (not separated into intrapartum and postpartum)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported. Method reported as block randomisation only

Allocation concealment (selection bias)

Unclear risk

Not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open label, participants would have been aware of allocation. Delivery nurse not blinded but all other hospital staff delivering care were blind

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

The data were retrieved from chart review and hospital staff were blinded apart from delivery room nurses.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5 women in the dexamethasone delivered after 1 week and were included in ITT analysis

Selective reporting (reporting bias)

Low risk

Relevant outcome data reported

Other bias

Low risk

The groups were comparable at baseline.

Balci 2010

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: computer‐generated random number table, sequential sealed envelopes, not stated if opaque
Stratification: none stated
Placebo: no, comparison was no treatment
Sample size calculation: not stated
Intention‐to‐treat analyses: yes
Losses to follow‐up: 30 infants with fetal distress, meconium‐stained liquor and who delivered within less than 24 h were excluded from the study (14 in control group, 16 in steroid group)
Funding: not stated

Participants

Location: Dept of Obstetrics and Gynecology, Hospital of Meram, Faculty of Medicine, Selcuk University, Konya, Turkey
Timeframe: January 2007 and May 2009.
Eligibility criteria: 34‐36 weeks' gestation based on LMP. If unsure dates, fetal biometric measurements of 33‐36 weeks on abdominal ultrasonography (done on admission). The mother had had at least 2 contractions lasting more than 30 seconds in 10 min on cardiotocography, and cervical dilatation > 3 cm with 80% effacement

Gestational age range: 34 + 0‐36 + 0 weeks
Exclusion criteria: obstetric complications (severe IUGR, pre‐eclampsia, placental abruption, placenta praevia), multiple pregnancies, those who had already received antenatal corticosteroid therapy, PROM, or suspicion of chorioamnionitis, fetal anomaly, fetal distress, severe systemic disease (heart disease, hyperthyroidism, hypothyroidism, renal disease, diabetes mellitus)
Total recruited: 100 (50 women and babies in each group)

Interventions

The treatment group received a single dose of 12 mg betamethasone IM.

The control group received no treatment.

Women who delivered at least 24 h after betamethasone administration were included in the study.

Outcomes

Apgar score at 1 and 5 minutes, need for resuscitation, development of RDS

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Generated by a computer"

Allocation concealment (selection bias)

Unclear risk

"Sequential sealed envelopes" not stated if opaque or not

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Due to comparison group receiving no treatment and treatment group receiving corticosteroids, blinding of participants and personnel would not have been possible.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors is not described.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

30 infants with fetal distress, meconium‐stained liquor and who delivered within less than 24 h were excluded from the study (14 in control group, 16 in steroid group). Intention‐to‐treat analysis was used

Selective reporting (reporting bias)

High risk

Maternal complications were not pre‐specified but were reported

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Block 1977

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: computer‐generated randomisation sequence. Coded drug boxes were provided.
Stratification: none stated
Placebo: yes, normal saline
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 14 (10%) women delivered elsewhere and were lost to follow‐up. 6 (4%) women were excluded from analyses as they failed to complete the protocol.
Funding: Schering Corporation, Kenilworth, New Jersey, USA; and The Upjohn Company, Kalamazoo, Michigan, USA

Participants

Location: Department of Gynecology and Obstetrics at the University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA
Timeframe: not stated in manuscript, the study is coded as 1970s for the review
Eligibility criteria: women with preterm labour and PROM
Gestational age range: not stated
Exclusion criteria: not stated
Total recruited: the number randomised to each group not stated. Data are available on 114 infants; 60 infants in the treatment arm and 54 infants in the control arm

Interventions

12 mg betamethasone IM repeated after 24 h if delivery had not occurred
Control group received 1 mL normal saline IM repeated after 24 h if delivery had not occurred.

If there was evidence of progressive cervical dilatation an alcohol infusion was given in order to attempt to delay delivery for at least 48 h. In women with PROM delivery was induced if serial white blood cell counts or temperatures became elevated regardless of time elapsed since drug administration.

Outcomes

Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, need for mechanical ventilation/CPAP)

Notes

This study included a third arm (125 mg methylprednisolone IM repeated after 24 h if delivery had not occurred). The data for the review report the betamethasone and control arms only. Overall data were available for 150 living infants, of whom 128 were preterm. Further information was requested from the study authors but there was no reply.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Computer generated randomisation sequence."

Allocation concealment (selection bias)

Low risk

"Consecutively numbered boxes containing randomly selected study drug or placebo."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Clinicians were never aware of the contents of the coded box. Placeob was saline so it is likely that participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

14 (10%) women delivered elsewhere and were lost to follow‐up. 6 (4%) women were excluded from analyses as they failed to complete the protocol (1 in the betamethasone group, 2 in the methylprednisolone group, and 3 in the control group).

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes.

Other bias

Unclear risk

Insufficient information to assess if other sources of bias exist.

Cararach 1991

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: FIS; Perinatal Section of SEGO

Participants

Location: Hospital Clinic, University of Barcelona, Spain
Timeframe: 1987‐1990
Eligibility criteria: women with PROM
Gestational age range: 28‐30 weeks
Exclusion criteria: none stated
Total recruited: 18 women and infants; 12 women and infants in the treatment arm and 6 women and infants in the control arm

Interventions

Type and dose of corticosteroid used in the treatment group is not stated
Control group received expectant management

Outcomes

Fetal/neonatal outcome reported (RDS)

Notes

Study only available as an abstract. Further information was requested from the study authors but there was no reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of participants and personnel not stated, although unlikely as placebo was not used

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up

Selective reporting (reporting bias)

Unclear risk

Study only available as an abstract

Other bias

Unclear risk

Study was only available as an abstract. Further information was requested from the study authors, but there was no reply

Carlan 1991

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 2 (8%) infants with documented pulmonary maturity and 5 (17%) women with subsequent sealed membranes were not analysed
Funding: not stated

Participants

Location: University of South Florida Medical School, Tampa, Florida, USA
Timeframe: not stated in manuscript, the study is coded as 1990s for the review
Eligibility criteria: women with PROM
Gestational age range: 24‐34 weeks
Exclusion criteria: not stated
Total recruited: the number randomised to each group is not stated. Data are available on 24 women and infants; 13 women and infants in the treatment arm and 11 women and infants in the control arm

Interventions

12 mg betamethasone IM repeated after 24 h and weekly thereafter until delivery or 34 weeks.
Control group received expectant management.

Outcomes

Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (RDS, birthweight, days of mechanical ventilation/CPAP) and health service outcomes reported (days in NICU, neonatal days in hospital, neonatal hospital cost). However due to lack of SD data only chorioamnionitis and RDS data were included in the review.

Notes

This study included a third arm (12 mg betamethasone IM 24‐hourly for 2 doses and 400 mcg methylprednisolone IV 8‐hourly for 6 doses, repeated weekly until delivery or 34 weeks. The data for the review report the betamethasone and control arms only. Further information was requested from the study authors but there was no reply.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of participants and personnel not stated, although unlikely as placebo was not used

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 (8%) infants with documented pulmonary maturity and 5 (17%) women with subsequent sealed membranes were not analysed

Selective reporting (reporting bias)

Unclear risk

SD data not stated so a number of outcomes are not able to be included in the review

Other bias

Unclear risk

Only available as an abstract. Full paper not published

Collaborative 1981

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Coded drug boxes with sequentially‐numbered vials containing study drug were used. Sealed envelope containing the identity of the contents of was attached to each vial "to be opened in emergency only in case of an emergency". The manuscripts do not state how often these were opened. Stratification: yes, within each hospital
Placebo: yes, identical appearance
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 2 (0%) infants in the control arm were lost to RDS follow‐up as neonates and 240 (37%) children were lost to follow‐up at age 3 (124 in the treatment arm and 116 in the control arm)
Funding: National Institutes of Health, USA

Participants

Location: 5 university hospitals in the USA
Timeframe: March 1977‐March 1980
Eligibility criteria: women at high risk of preterm delivery. L/S ratio < 2.0 in cases of uncertain gestation, hyperthyroidism, hypertension, placental insufficiency, drug addiction, methadone use or gestational age > 34 weeks
Gestational age range: 26‐37 weeks
Exclusion criteria: > 5 cm of cervical dilatation, anticipated delivery < 24 h or > 7 d, intrauterine infection, previous glucocorticoid treatment, history of peptic ulcer disease, active tuberculosis, viral keratitis, severe fetal Rhesus sensitisation, infant unlikely to be available for follow‐up
Total recruited: 696 women and 757 infants; 349 women and 378 infants in the treatment arm and 347 women and 379 infants in the control arm

Interventions

4 doses of 5 mg dexamethasone phosphate IM 12 h apart
Control group received placebo

Outcomes

Maternal outcomes (postnatal fever), fetal/neonatal outcomes (fetal death, neonatal death, RDS, birthweight, interval between trial entry and delivery, systemic infection in the first 48 h of life, proven infection while in the NICU, necrotising enterocolitis), childhood outcomes (death, lung function, developmental delay, intellectual impairment, cerebral palsy) and health service outcomes were reported (length of neonatal hospitalisation)

Notes

Further information was requested from the authors but there was no reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

High risk

Sealed envelope containing the identity of the contents of was attached to each vial "to be opened in emergency only in case of an emergency". The manuscripts do not state how often these were opened.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"Both placebo and steroid were dispensed as 10 ml clear, colourless solutions which differed only in that one contained the steroid". It is likely that participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

2 (0.27%) infants in the control arm were lost to RDS follow‐up as neonates. At age 3, 240 (37%) children were lost to follow‐up (124 in the treatment arm and 116 in the control arm), or had died (47 in the treatment arm and 46 in the control arm).

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Dexiprom 1999

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: computer‐generated randomisation. Sequentially‐numbered drug boxes were used. Stratification: yes, by hospital
Placebo: yes, normal saline
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 7 (3%) women and infants were excluded from analysis (3 women did not have PROM, 2 women were < 26 weeks at randomisation, 1 woman received off‐protocol corticosteroid, a neonatal bed was not available in 1 case)
Funding: Medical Research Council, South Africa; Donmed Pharmaceuticals, South Africa

Participants

Location: 6 hospitals in South Africa
Timeframe: not stated in the manuscripts, the study is coded as 1990s for the review
Eligibility criteria: women with PROM between 28‐34 weeks or with an estimated fetal weights of 1000 g‐2000 g if the gestational age was unknown
Gestational age range: 28‐34 weeks
Exclusion criteria: cervical dilatation > 4 cm, evidence of infection, evidence of antepartum haemorrhage, < 19 years old
Total recruited: 204 women and 208 infants; 102 women and 105 infants in the treatment arm and 102 women and 103 infants in the control arm

Interventions

2 doses of 12 mg dexamethasone IM 24 h apart
Control group received placebo

All women also received ampicillin, metronidazole and hexoprenaline if contractions present in < 24 h

Outcomes

Maternal outcomes (maternal death, chorioamnionitis, endometritis, postnatal fever), fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, IVH, birthweight, need for mechanical ventilation/CPAP, systemic infection in the first 48 h of life, necrotising enterocolitis)

Notes

Study authors supplied additional data

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation

Allocation concealment (selection bias)

Low risk

Central allocation. Sequentially‐numbered drug boxes were used

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of participants likely as identical looking placebo was used. Blinding of study personnel was not described, other than "double blind".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7 (3%) women and infants were excluded from analysis (3 women did not have PROM, 2 women were < 26 weeks at randomisation, 1 woman received off‐protocol corticosteroid, a neonatal bed was not available in 1 case)

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Study was discontinued before target sample size was reached due to increasing body of evidence of the use of corticosteroids in women with PPROM being advantageous to the infants, and it was felt unnecessary to conduct further trials of antenatal corticosteroids in women with PPROM

Doran 1980

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Coded drug boxes were provided. Randomisation code was kept on file at the Pharmacy Department of Toronto General Hospital. Stratification: yes, by gestational age into 2 subgroups; 24‐32 weeks and 33‐34 weeks
Placebo: yes, vehicle of steroid preparation consisting of 0.2 mg benzalkonium chloride and 0.1 mg disodium edentate per mL
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: The Hospital for Sick Children Foundation, Canada; Schering Corporation, Canada; Ontario Ministry of Health Provincial Research Grant PR 279, Canada

Participants

Location: 6 teaching hospitals in Toronto, Canada
Timeframe: January 1975‐June 1978
Eligibility criteria: women with PROM, spontaneous preterm labour or planned preterm delivery
Gestational age range: 24 and 34 weeks.
Exclusion criteria: women with pre‐eclampsia or in whom steroids were contraindicated on medical grounds.
Total recruited: 137 women and 144 infants; 75 women and 81 infants in the treatment arm and 62 women and 63 infants in the control arm

Interventions

4 doses of 3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate IM 12 h apart
Control group received 4 doses of identical placebo

Outcomes

Fetal/neonatal outcomes were reported (fetal death, neonatal death, RDS, IVH, birthweight, days of mechanical ventilation)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Low risk

Coded drug boxes were provided. Randomisation code was kept on file at the Pharmacy Department of Toronto General Hospital.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is likely that participants were blinded as both placebo and corticosteroid solutions were identical. Blinding of study personnel was not described other than to state "double blind".

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome assessors was not described, but is likely as the authors state "The key to the code was not broken until the whole study was completed".

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist

Fekih 2002

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, number of post‐randomisation exclusions not stated
Funding: not stated

Participants

Location: CHU Farhat Hached, Sousse, Tunisia
Timeframe: January 1998‐June 1999
Eligibility criteria: women in preterm labour
Gestational age range: 26‐34 weeks
Exclusion criteria: gestational diabetes, > 4 cm cervical dilatation, fetal abnormalities, contraindication to corticosteroids, delivery elsewhere or after 34 weeks (post‐randomisation exclusions)
Total recruited: 118 women and 131 infants; 59 women and 63 infants in the treatment arm and 59 women and 68 infants in the control arm

Interventions

Abstract and full report state slightly different protocols for the intervention arm. The abstract stated that 24 mg betamethasone was given as two 12 mg IM doses at 24 h apart. The full text states that this regimen was repeated weekly. Women had two doses of 12 mg given 24 h apart, and this regimen was repeated weekly.
Control group received expectant management

Outcomes

Maternal outcomes (chorioamnionitis, postnatal fever) and fetal/neonatal outcomes reported (neonatal death, RDS, IVH)

Notes

Article in French, abstract in English. Article translated by review authors (La Tunisie Medicale, 2002, Vol 80; No. 5: 260‐265). Further information was requested from the study authors but there was no reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment was not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding is unlikely as placebo was not used

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Number of post‐randomisation exclusions not stated

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist

Gamsu 1989

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: yes, by hospital
Placebo: yes, vehicle of betamethasone preparation
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: Glaxo Group Research Ltd, Greenford, Middlesex, UK

Participants

Location: 11 hospitals in the UK
Timeframe: mid 1975‐February 1978
Eligibility criteria: women with spontaneous or planned preterm delivery
Gestational age range: < 34 weeks
Exclusion criteria: contraindication to corticosteroids, contraindications to postponing delivery, diabetes, suspected intrauterine infection
Total recruited: 251 women and 268 infants; 126 women and 131 infants in the treatment arm and 125 women and 137 infants in the control arm

Interventions

6 doses of 4 mg betamethasone phosphate IM 8 h apart
Control group received 6 doses of placebo

All women with spontaneous labour received IV salbutamol

Outcomes

Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, IVH, birthweight, systemic infection in the first 48 h of life)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is likely that participants were blinded as placebo was used. Blinding of study personnel was not described other than "double‐blind".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up reported

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist

Garite 1992

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: random‐number table generated randomisation sequence by pharmacy. The pharmacy provided consecutive sealed envelopes. Stratification: none stated
Placebo: yes, normal saline
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 5 (7%) women delivered elsewhere and were lost to follow‐up (4 in treatment arm and 1 in control arm)
Funding: Long Beach Memorial Foundation, USA

Participants

Location: Long Beach Memorial Women's Hospital, California, USA
Timeframe: December 1984‐May 1990
Eligibility criteria: women likely to deliver between 24 h and 7 d with spontaneous preterm labour or planned preterm delivery
Gestational age range: 24‐27 + 6 weeks
Exclusion criteria: PROM, clinical or laboratory evidence of infection, contraindication to or previously given corticosteroids, diabetes
Total recruited: 76 women and 82 infants; 37 women and 40 infants in the treatment arm and 39 women and 42 infants in the control arm

Interventions

2 doses of 6 mg betamethasone acetate and 6 mg betamethasone phosphate IM 24 h apart, repeated weekly if still < 28 weeks and thought likely to deliver within the next week
Control group received 2 doses of placebo. Women undelivered after 28 weeks and 1 week post their last dose of study medication were allowed glucocorticoids at the discretion of their physicians.

Outcomes

Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, Apgar < 7, need for mechanical ventilation/CPAP, duration of mechanical ventilation/CPAP, proven neonatal infection while in NICU)

Notes

It is not stated how many women received corticosteroids off protocol.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random‐number table generated randomisation sequence by pharmacy

Allocation concealment (selection bias)

Unclear risk

The pharmacy provided consecutive sealed envelopes, not stated if envelopes were opaque

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is likely that participants were blinded as placebo was used. Blinding of study personnel was not described other than "double‐blind"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5 (7%) women delivered elsewhere and were lost to follow‐up (4 in treatment arm and 1 in control arm).

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

It is not stated how many women received corticosteroids off protocol.

Goodner 1979

Study characteristics

Methods

Type of study: RCT (abstract)
Method of treatment allocation: not described

Stratification: not described
Placebo: yes, saline
Sample size calculation: not stated
Intention‐to‐treat analyses: not stated
Losses to follow‐up: not stated
Funding: not stated

Participants

Location: Temple University Hospital, Philadelphia, Pennsylvania, USA
Timeframe: July 1976‐July 1978
Eligibility criteria: any pregnant woman expected to deliver prior to 34 weeks' gestation between July 1976 and July 1978 at Department of Obs & Gyne at Temple University Hospital
Gestational age range: prior to 34 weeks
Exclusion criteria: not stated
Total recruited: 45 placebo, 47 steroids

Interventions

Treatment group received an IM injection of betamethasone. The control group received an IM injection of saline as placebo.

Outcomes

Neonatal mortality, RDS

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated other than "randomized"

Allocation concealment (selection bias)

Unclear risk

Not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Likely that participants were blinded and possible that study personnel were blinded due to the use of placebo

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessor not stated

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not stated

Selective reporting (reporting bias)

High risk

RDS is the only outcome reported.

Other bias

Unclear risk

Only available as an abstract ‐ does not appear to have been published

Gyamfi‐Bannerman 2016

Study characteristics

Methods

Type of study: double‐blind, RCT
Method of treatment allocation: simple urn method of randomisation

Stratification: yes, according to clinical site and gestational age (34‐35 weeks and 36 weeks)
Placebo: yes, matching placebo
Sample size calculation: yes
Intention‐to‐treat analyses: yes
Losses to follow‐up: yes, 4 (0.11%) lost to follow‐up; 2 in each treatment group
Funding: National Heart, Lung, and Blood Institute, USA; Eunice Kennedy Shriver National Institute of Child Health and Human Development, USA; National Center for Advancing Translational Sciences, National Institutes of Health, USA

Participants

Location: 17 university‐based clinics in the USA. All centres affiliated with the Maternal–Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Timeframe: October 2010‐February 2015
Eligibility criteria: women with singleton pregnancy 34 weeks + 0 d‐36 weeks + 5 d gestation at "high probability" of preterm delivery. "High probability was defined as either preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement, or spontaneous rupture of the membranes. If neither of these criteria applied, a high probability was defined as expected preterm delivery for any other indication either through induction or cesarean section between 24 h and 7 d after the planned randomisation, as determined by the obstetrical provider."
Gestational age range: 34 weeks + 0 d‐36 weeks + 5 d
Exclusion criteria: expected delivery < 12 h for any reason, already received antenatal corticosteroids in current pregnancy, chorioamnionitis, 8 cm or more cervical dilation, non‐reassuring fetal status requiring immediate delivery, no gestational age dating by ultrasound before 32 weeks for women with known date for last menstrual period, women without ultrasound dating before 24 weeks' gestation with unknown date of last menstrual period
Total recruited: 2831 women and 2831 infants; 1429 women and 1429 infants in the treatment arm and 1402 women and 1402 infants in the control arm

Interventions

Treatment group: (n = 1429 randomised) 2 IM injections of 12 mg betamethasone (equal parts betamethasone sodium phosphate and betamethasone acetate) administered 24 h apart

Control group received matching placebo

"For those enrolled because of an indication for preterm delivery, labor inductions were expected to start by 36 weeks 5 d, and cesarean deliveries were to be scheduled by 36 weeks 6 days and not before 24 hours after randomization."

Control: (n = 1402 randomised) placebo IM injections as above

Follow up: to 28 d for oxygen dependency outcome

Outcomes

Maternal outcome (maternal death, chorioamnionitis, side effects of therapy in women), fetal/neonatal outcomes (perinatal death, fetal death, neonatal death, RDS, IVH, birthweight, necrotising enterocolitis, proven infection while in NICU, need for mechanical ventilation/CPAP, surfactant use, air leak syndrome, Apgar score < 7, small for gestation age, admission to NICU)

We asked study authors to clarify the mechanical ventilation/CPAP data presented in Table 2 of the publication; we are unsure if outcome categories are exclusive or not. We have not included data from this trial in the meta‐analysis for 1.25 due to these concerns; data will be included at the next update if confirmed by study authors

Data from trial is available for following non‐review outcomes: maternal serious adverse events, infant serious adverse events, hypoglycaemia in infant. Length of stay (maternal and infant) reported as median with IQR only. Randomisation to delivery interval reported as median with IQR only

Notes

Supplementary appendix published online with data tables and additional information on trial methods relevant to risk of bias. Contact author confirmed no maternal deaths and blinding of researchers abstracting data from maternal and neonatal charts (24.2.2016 by email)

ClinicalTrials.gov number, NCT01222247.

Ruptured membranes occurred in 22.1% intervention and 21.7% controls

  1. No stillbirths or deaths within 72 hours

  2. "Adverse events that were reported after both injections were less common in the betamethasone group than in the placebo group (rate after first injection, 14.1% vs. 20.3%; P<0.001; rate after second injection, 5.5% vs. 9.5%; P<0.007). Almost all adverse events (95%) were local reactions at the injection site (Table S4 in the Supplementary Appendix)." These data were used for our review's side effects outcome

  3. "Serious maternal adverse events occurred in 10 women in the betamethasone group and 12 in the placebo group (Table S7 in the Supplementary Appendix). Apart from the neonatal deaths, only one serious neonatal adverse event occurred (a case of thrombocytopenia in the betamethasone group)." These data were reported narratively above.

"A total of 860 of 1429 women (60.2%) in the betamethasone group and 826 of 1402 (58.9%) in the placebo group received the prespecified two doses of study medication. Of the 1145 women who did not receive a second dose, 1083 (94.6%) delivered before 24 hours; 6 women did not receive any of the assigned study medication. (In the placebo group, 3 women who consented to participate in the trial subsequently declined the injection, 1 woman delivered after randomization but before the first dose, and 1 received open label betamethasone. In the betamethasone group, 1 woman was in active labor with complete cervical dilation at the time of randomization.)"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Independent data‐coordinating centre with the use of the simple urn method, with stratification according to clinical site and gestational age category (34 to 35 weeks vs. 36 weeks)"

Allocation concealment (selection bias)

Low risk

Remote centre performed randomisation and packaged intervention and placebo

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Identical treatment and placebo packs prepared remotely. Women and staff blinded

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Trained research staff extracted data from maternal and neonatal staff; authors confirmed by email that these researchers were blinded. Charts of babies admitted to special care were reviewed by blinded staff for respiratory outcomes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Two women in each group lost to follow‐up. Data available for 2827 neonates

Selective reporting (reporting bias)

Low risk

Supplementary outcome data published online with paper

Other bias

Low risk

Few baseline imbalances apart from mean maternal age (28.6 vs. 27.8 years) and Hispanic ethnic background (28.3 vs. 32%)

Kari 1994

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: yes, according to gestational age (24‐27.9 weeks and 28‐31.9 weeks) at each hospital
Placebo: yes, normal saline
Sample size calculation: yes
Intention‐to‐treat analyses: yes
Losses to follow‐up: yes, 10 (11%) children in the follow‐up study at age 2 (2 in the treatment arm and 8 in the control arm)
Funding: Foundation for Pediatric Research, Finland; Orange County Infant Care Specialists, Finland; The Orion Corporation Research Foundation, Finland; Instrumentarium Corporation Research Foundation, Finland; Arvo and Lea Ylppo Foundation, Finland; Rinnekoti Foundation, Finland; and Organon Company, Oss, The Netherlands

Participants

Location: 5 hospitals in Finland
Timeframe: April 1989‐October 1991
Eligibility criteria: women with preterm labour or threatened preterm delivery due to pre‐eclampsia
Gestational age range: 24‐31.9 weeks
Exclusion criteria: rupture of membranes, chorioamnionitis, congenital abnormalities, proven lung maturity, insulin‐treated diabetes, previously treated with corticosteroids
Total recruited: 157 women and 190 infants; 77 women and 95 infants in the treatment arm and 80 women and 95 infants in the control arm

Interventions

4 doses of 6 mg dexamethasone sodium phosphate IM 12 h apart
Control group received 4 doses of placebo. Rescue treatment with exogenous human surfactant was given to infants born 24‐33 weeks, who at 2‐24 h of age required mechanical ventilation with > 40% oxygen for RDS.

Outcomes

Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, surfactant use, necrotising enterocolitis, small‐for‐gestational age) and childhood outcomes reported (death, neurodevelopmental delay)

Notes

Efficacy analysis restricted to 91 infants in treatment arm and 88 infants in control arm. 3 infants excluded for protocol violations (1 mother with twins in placebo arm was given corticosteroid, 1 infant in the treatment arm developed RDS but was not given surfactant as it was not available) and 6 infants were excluded because of congenital malformations (2 treatment, 4 placebo)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated. "Randomisation in each participating hospital was performed in blocks of 10"

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"The investigators and those who provided care were unaware of the treatment allocation". It is likely that participants were blinded as "ampoules containing betamethasone and placebo were identical".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

10 (11%) children in the follow‐up study at age 2 (2 in the treatment arm and 8 in the control arm). 1 female placebo‐treated infant born at 27 weeks' gestation died 3 months after the expected date of delivery, 4 infants were lost due to parental refusal, 2 were living overseas, and 3 were in other regions of the country

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Efficacy analysis restricted to 91 infants in treatment arm and 88 infants in control arm. 3 infants excluded for protocol violations (1 mother with twins in placebo arm was given corticosteroid, 1 infant in the treatment arm developed RDS but was not given surfactant as it was not available) and 6 infants were excluded because of congenital malformations (2 treatment, 4 placebo)

Khazardoust 2012

Study characteristics

Methods

Type of study: double‐blind RCT
Method of treatment allocation: computer generated

Stratification: none stated
Placebo: yes, placebo‐controlled
Sample size calculation: not described
Intention‐to‐treat analyses: no, 5 (13%) of participants in the intervention arm were excluded from analysis post randomisation
Losses to follow‐up: yes, as above
Funding: "The study was supported by Tehran University of Medial Sciences. The assays were
performed At Shahed University of Medical Sciences which we would like to thanks the
staff and cooperation of that center in this study."

Participants

Location: Obstetric emergency department of Vali‐e‐Asr,Hospital, Tehran, Iran

Timeframe: June 2006 to July 2010

Eligibility criteria: patients at risk of preterm labor as determined by routine ultrasound examination in the first trimester

Gestational age range: 34‐37 weeks
Exclusion criteria: only primigravid women with signs of preterm labour were eligible, including "palpable uterine contractions every 5‐8 minutes and Bishop score of 4 and higher associated with cervical dilatation of more than 1 cm and at least 50% of effacement."

"Women with systemic diseases, maternal hypertension before or during pregnancy, uterine tenderness, chorioamnionitis signs, symptomatic vaginal infection, rupture of membranes, current use of antibiotics, induced pregnancy, and history of smoking were excluded."
Total recruited: 80 women and 80 infants; 40 women and 40 infants in the treatment arm and 40 women and 40 infants in the control arm

Interventions

The treatment group received 2 doses of 12 mg betamethasone IM.

The control group received placebo of saline as per regimen above.

Outcomes

No outcomes available for the review

Notes

Data are provided on endocervical cytokine levels in women who delivered within and after 1 week but no outcome data available for the review are presented

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation sequence in blocks of 4

Allocation concealment (selection bias)

Unclear risk

Only 1 person (research assistant) had access to the randomisation list. It is unclear whether this person was part of the team performing the study

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Placebo‐controlled trial ‐ saline was used as the placebo

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described

Incomplete outcome data (attrition bias)
All outcomes

High risk

Analysis was not by intention‐to‐treat. 5 participants in the intervention arm were excluded for named reasons and their data were not included

Selective reporting (reporting bias)

Low risk

All intended outcomes, i.e. cytokine measurements, were reported

Other bias

High risk

Data were analysed for 35 women in the intervention arm versus 40 in the control arm because 2 delivered before cytokine sampling after the second dose of betamethasone, 1 opted out of the study and 2 developed high blood pressure

Lewis 1996

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: random‐number table generated randomisation sequence by clinical research nurse uninvolved in clinical care. Sequentially‐numbered sealed opaque envelopes used. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 2 (2%) women left hospital after randomisation and were lost to follow‐up (1 woman in each arm)
Funding: not stated

Participants

Location: Louisiana State University Medical Center, Shreveport, Louisiana, USA
Timeframe: not stated in manuscript, the study is coded as 1990s for the review
Eligibility criteria: women with singleton pregnancies with PROM. Women were randomised 12‐24 h after receiving IV ampicillin‐sulbactam
Gestational age range: 24‐34 weeks
Exclusion criteria: evidence of infection, vaginal examination, cerclage, allergic to penicillin, contraindication to expectant management, lung maturity confirmed by L/S ratio if 32 weeks or more
Total recruited: 79 women and infants; 39 women and infants in the treatment arm and 40 women and infants in the control arm

Interventions

The treatment group received 12 mg IM betamethasone repeated at 24 h and weekly if the women had not delivered.
The control group received expectant management.

Outcomes

Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes (neonatal death, RDS, IVH, birthweight, Apgar < 7, interval between trial entry and delivery, admission to NICU, surfactant use, proven neonatal infection while in NICU, necrotising enterocolitis) and health service outcome reported (length of neonatal hospitalisation)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Clinical research nurse uninvolved in clinical care generated randomisation sequence by using random‐number table, with a random permuted block size of 10

Allocation concealment (selection bias)

Low risk

Sequentially‐numbered sealed opaque envelopes were used

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comparison was "no treatment" so blinding not possible

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 (2%) women left hospital against medical advice after randomisation and were lost to follow‐up (1 women in each arm)

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist

Liggins 1972b

Study characteristics

Methods

Type of study: RCT

Method of treatment allocation: random‐number table generated randomisation sequence by chief pharmacist. Pharmacy provided coded drug ampoules containing treatment or placebo

Stratification: no

Placebo: yes, of identical appearance

Sample‐size calculation: no

Intention‐to‐treat analyses: yes

Losses to follow‐up: yes, 54 (18%) children in the follow‐up study at ages 4‐6 years (31 in the treatment arm and 23 in the control arm) and 412 (44%) adults in the follow‐up study at age 30 years (219 in the treatment arm and 193 in the control arm)

Funding: Health Research Council of New Zealand, Auckland, New Zealand; Auckland Medical Research Foundation, Auckland, New Zealand; and New Zealand Lottery Grants Board, Wellington, New Zealand

Participants

Location: National Women's Hospital, Auckland, New Zealand

Timeframe: December 1969 and February 1974

Eligibility criteria: women with threatened or planned preterm delivery

Gestational age range: 24‐36 weeks

Exclusion criteria: imminent delivery, contraindication to corticosteroids

Total recruited: 1142 women and 1218 infants; 560 women and 601 infants in the treatment arm and 582 women and 617 infants in the control arm

Interventions

The treatment group 2 doses of 6 mg betamethasone phosphate and 6 mg betamethasone acetate IM 24 h apart. After the first 717 women had enrolled, the treatment intervention was doubled to 2 doses of 12 mg betamethasone phosphate and 12 mg betamethasone acetate IM 24 h apart.
The control group received 6 mg cortisone acetate, which has 1/70th of the corticosteroid potency of the betamethasone.

Outcomes

Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, cerebroventricular haemorrhage, mean birthweight, Apgar score < 7, mean interval between trial entry and delivery, proven infection while in NICU), childhood outcomes (death, mean weight, mean height, mean head circumference, mean lung function, mean blood pressure, intellectual impairment, cerebral palsy) and adulthood outcomes were reported (death, mean weight, mean height, mean head circumference, mean skin fold thickness, mean blood pressure, glucose impairment, HPA axis function, mean cholesterol, educational achievement, visual impairment, hearing impairment, intellectual impairment)

Notes

Review includes new intention‐to‐treat analysis of the complete study and additional data due to the study authors providing individual participant study records

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random‐number table generated randomisation sequence by chief pharmacist

Allocation concealment (selection bias)

Low risk

Pharmacy provided coded drug ampoules containing treatment or placebo

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of study personnel was not described. It is likely that participants were blinded as placebo was of identical appearance to the corticosteroid.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

For the diagnosis of RDS, clinical records and chest radiographs were assessed separately and independently, by 1 of the study authors, and by a radiologist.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Incomplete outcome data for 54 (18%) children in the follow‐up study at ages 4‐6 (31 in the treatment arm and 23 in the control arm) and 412 (44%) adults in the follow‐up study at age 30 (219 in the treatment arm and 193 in the control arm)

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Lopez 1989

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: not described

Stratification: not stated
Placebo: no.
Sample size calculation: not stated
Intention‐to‐treat analyses: not stated however, all those randomised were analysed
Losses to follow‐up: nil
Funding: not stated

Participants

Location: Department of Obstetrics and Gynecology, Faculty of Medicine, National Univeristy of Colombia
Timeframe: August 1983‐December 1985
Eligibility criteria: PROM (confirmed using speculoscopy and ultrasound), no signs of infection, not in labour at time of hospitalisation
Gestational age range: 27‐35 weeks' gestation
Exclusion criteria: not stated
Total recruited: 20 control group, 20 study group

Interventions

The treatment group received 2 doses of 12 mg betamethasone IM, 12 h apart.

The control group received no treatment.

Outcomes

Neonatal mortality, RDS, Apgar score < 7 at 5 min, systemic infection in first 48 h

Notes

Original article in Spanish, translated into English

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated other than "patients were classified randomly into groups"

Allocation concealment (selection bias)

Unclear risk

Not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Comparison is "no treatment" so blinding not possible

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up reported

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Mansouri 2010

Study characteristics

Methods

Type of study: double‐blind RCT
Method of treatment allocation: not described

Stratification: not stated
Placebo: yes, placebo‐controlled
Sample size calculation: not stated
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated in translation

Double‐blind, randomised controlled trial in Kurdistan University of Medical Sciences, Sanandaj, Iran

Participants

Location: Kurdistan University of Medical Sciences, Sanandaj, Iran
Timeframe: "during 2007" stated
Eligibility criteria: women at high risk of preterm labour, not described
Gestational age range: 35‐36 weeks
Exclusion criteria: not stated in our translation
Total recruited: 200 women and 200 infants; 100 women and 100 infants in the treatment arm and 100 women and 100 infants in the control arm

Interventions

The treatment group received 2 doses of 12 mg betamethasone, IM.

The control group received a placebo of normal saline.

Outcomes

Maternal outcome (maternal death, maternal infections), fetal/neonatal outcomes reported (RDS, birthweight, necrotising enterocolitis, systemic infection in the first 48 h of life, need for mechanical ventilation/CPAP, Apgar < 7 at 5 min, admission to NICU)

Notes

Original article in Persian; we have obtained a truncated translation for this update. Our translator was unable to translate the definition of respiratory distress syndrome but said that the outcome was based on defined symptoms and confirmed by a paediatrician.

Additonal outcome data for this trial are:

Maternal length of stay > 3 d (equal numbers in treatment arms) is reported narratively above: mean birthweight and SD in kg has been analysed as g.

Data for the trial outcome of 'need for respiratory support' has been included in the review analysis 1.26 'need for mechanical ventilation'.

We have been unable to confirm whether the trial included only singleton pregnancy, but this is suggested by the equal numbers of women and infants reported. We have included data from this trial in the singleton subgroup.

We had no information about membrane status from our translation, and so this trial has been included in the 'not reported or mixed population subgroup.'

Maternal length of stay > 3 d (equal numbers in both arms) is reported narratively.

We emailed study investigators for clarification and additional information with no reply (2/2016).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Generation of sequence not stated, but block method specified

Allocation concealment (selection bias)

Unclear risk

Not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Trial described as double‐blind. Placebo‐controlled trial, and researchers and women were blind to treatment

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Neonatal outcomes extracted by blinded paediatrician.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data reported for all women randomised

Selective reporting (reporting bias)

Low risk

Relevant outcome data reported

Other bias

Unclear risk

We have obtained a basic translation, but future correspondence with authors may clarify some of the risk of bias domains above.

Morales 1989

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Sealed envelopes were used. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: no
Funding: not stated

Participants

Location: 3 hospitals in Florida, USA
Timeframe: January 1986‐March 1988
Eligibility criteria: women with singleton pregnancies with PROM
Gestational age range: 26 and 34 weeks
Exclusion criteria: PROM < 12 h before onset of labour, uterine tenderness, foul smelling lochia, fetal tachycardia, allergy to penicillin, congenital abnormalities, L/S ratio 2 or more, unable to obtain an L/S ratio, Dubowitz‐assigned gestational age different from obstetric assessment by 3 weeks (post‐randomisation exclusion)
Total recruited: 165 women and infants; 87 women and infants in the treatment arm and 78 women and infants in the control arm

Interventions

4 treatment arms. Group 1, expectant management. Group 2, expectant management plus 2 doses of 12 mg betamethasone IM 24 h apart, repeated weekly if the women remained undelivered. Group 3, expectant management plus 2 g ampicillin IV every 6 h until cervical cultures were negative. Group 4, combination of group 2 and 3 management. We combined Groups 2 and 4 in the treatment arm for the review, and groups 1 and 3 in the control arm for the review.

Outcomes

Maternal outcome (chorioamnionitis), fetal/neonatal outcomes reported (neonatal death, RDS, chronic lung disease, IVH, birthweight, proven neonatal infection while in NICU, necrotising enterocolitis, duration of mechanical ventilation/CPAP)

Notes

Further information requested from study authors but there was no reply. No information was available on post‐randomisation exclusions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

"Sealed envelopes" were used. Not further described

Blinding of participants and personnel (performance bias)
All outcomes

High risk

As comparison was expectant management, blinding of participants and personnel was not possible

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No losses to follow‐up noted. No information was available on post‐randomisation exclusions as per exclusion criteria

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist

Nelson 1985

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: random‐number table generated randomisation sequence with consecutive sealed envelopes used. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated

Participants

Location: Wake Forest University Medical Center, North Carolina, USA
Timeframe: not stated in manuscript, the study is coded as 1980s for the review
Eligibility criteria: women with PROM
Gestational age range: 28 and 34 weeks
Exclusion criteria: fetal distress, active labour, cervical dilatation > 3 cm, sensitivity to tocolytics, PROM > 24 h, existing infection
Total recruited: 44 women and infants; 22 women and infants in each arm

Interventions

3 treatment arms. Group 1, 2 doses of 6 mg or 12 mg betamethasone IM 12 h apart, delivery 24‐48 h after PROM and after 24 h of corticosteroid therapy. Group 2, delivery 24‐48 h after PROM. Group 3, expectant management. We did not include Group 3 in the review.

Outcomes

Fetal/neonatal outcomes (neonatal death, RDS, proven neonatal infection while in NICU) and health service outcome reported (length of neonatal hospitalisation)

Notes

Authors provided further information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random‐number table generated randomisation sequence

Allocation concealment (selection bias)

Unclear risk

Consecutive sealed envelopes were used, not stated if opaque

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of participants and personnel was not possible due to the nature of the comparison.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up or exclusions

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Parsons 1988

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated

Participants

Location: University of Illinois, Chicago, USA
Timeframe: not stated in manuscript, the study is coded as 1980s for the review
Eligibility criteria: women with PROM and < 4 cm of cervical dilatation
Gestational age range: 25‐32 weeks
Exclusion criteria: infection, fetal distress, fetal anomalies, contraindication to tocolysis
Total recruited: 45 women and infants; 23 women and infants in the treatment arm and 22 women and infants in the control arm

Interventions

The treatment group received 2 doses of 12 mg betamethasone IM 12 h apart repeated weekly until 32 weeks.
The control group received expectant management.

Outcomes

Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, systemic infection in the first 48 h of life, proven neonatal infection while in NICU)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of participants and personnel was not possible due to the nature of the comparison.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up or exclusions described

Selective reporting (reporting bias)

Low risk

Pre‐specified outcomes were reported.

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Porto 2011

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: sealed cardboard boxes numbered according to random number table generated by a statistician not involved in the study

Stratification: not stated
Placebo: yes, identical to corticosteroid in appearance, volume and colour
Sample size calculation: yes
Intention‐to‐treat analyses: yes
Losses to follow‐up: 43 (13%) women (19 in corticosteroid group and 24 in placebo group) were discharged from hospital still pregnant and were considered post‐randomisation loss to follow‐ups. 2 (1%) women were excluded from the placebo group as they were found to be ineligible after randomisation (multiple pregnancy, and term pregnancy). Two infant stillbirths were also excluded.
Funding: supported by the Insitiuto de Medicina Integral Prof Fernando Figueira‐IMIP, a private, not for profit healthcare organisation based in Recife, Brazil. The Institute did not interfere with study design or analysis.

Participants

Location: Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil
Timeframe: April 2008‐June 2010
Eligibility criteria: 34‐36 + 6 weeks' gestation at risk of imminent premature delivery (either spontaneously or if early delivery was recommended as a result of problems with mother or fetus)
Gestational age range: 34‐36 + 6 weeks' gestation
Exclusion criteria: multiple pregnancy, major congenital malformations, haemorrhage symptoms with active bleeding, clinical evidence of chorioamnionitis, previous use of antenatal corticosteroids, need for immediate resolution of pregnancy for maternal or fetal reasons
Total recruited: 320 women and infants; 163 women and infants in the treatment arm and 157 women and infants in the control arm

Interventions

The treatment group received 2 doses of 12 mg IM betamethasone 24 h apart.

The control group received IM saline as placebo.

Outcomes

Maternal outcomes (side effects of therapy in women) and fetal/neonatal outcomes (fetal deaths, neonatal deaths, RDS, birthweight, proven infection while in NICU, need for mechanical ventilation/CPAP, mean duration of mechanical ventilation/CPAP, surfactant use, small for gestational age, admission to NICU)

Notes

For infant outcomes we have used the denominator stated in the published report excluding women who left the trial pregnant. An intention‐to‐treat analysis should have included these women, so for SOF outcomes we carried out a sensitivity analysis to determine if the denominator used made a difference to the overall pooled effect estimate; it did not (data not shown)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table was prepared by a statistician not involved in the study, using random allocation software

Allocation concealment (selection bias)

Low risk

The hospital pharmacy prepared sealed cardboard boxes numbered according to the random number table, and containing either betamethasone or placebo, identical in appearance, volume and colour.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Investigators, physicians caring for the women, the women themselves and the statistician were all blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Investigators, physicians caring for the women, the women themselves and the statistician were all blinded.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

43 (13%) women (19 in steroid group and 24 in placebo group) were discharged from hospital still pregnant and were considered post‐randomisation losses to follow‐up. 2 (1%) women were excluded from the placebo group as they were found to be ineligible after randomisation (multiple pregnancy, and term pregnancy).

Selective reporting (reporting bias)

Low risk

All pre‐specified outcomes appear to have been reported.

Other bias

Unclear risk

States "no significant differences between groups in most baseline characteristics," but does not report where differences exist.

Qublan 2001

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: random‐number table generated randomisation sequence Allocation concealment unclear. Stratification: none stated
Placebo: no
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated

Participants

Location: 2 military hospitals in Jordan
Timeframe: January 1997‐February 1999
Eligibility criteria: women with singleton pregnancies and PROM
Gestational age range: 27‐34 weeks
Exclusion criteria: lethal congenital anomaly, fetal death, infection, expected delivery within 12 h
Total recruited: 139 women and infants; 72 women and infants in the treatment arm and 67 women and infants in the control arm

Interventions

The treatment group received 4 doses of 6 mg dexamethasone IM 12 h apart, repeated if women had not delivered after 1 week.
The control group received expectant management.

Outcomes

Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, IVH, proven neonatal infection while in NICU, necrotising enterocolitis, Apgar < 7) and health service outcome reported (length of neonatal hospitalisation)

Notes

Study authors contacted for further information but no reply. Discrepancy in number of infants with necrotising enterocolitis in manuscript

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random‐number table generated randomisation sequence.

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of participants and personnel was not possible due to the nature of the comparison.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessment was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up or exclusions stated

Selective reporting (reporting bias)

Unclear risk

Discrepancy in number of infants with necrotising enterocolitis in manuscript

Other bias

Unclear risk

Funding source not stated

Schutte 1980

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Coded drug ampoules were provided. Randomisation code was only known to pharmacist. Stratification: none stated
Placebo: yes, normal saline
Sample size calculation: no
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, 12 (12%) children in the follow‐up study at ages 10‐12 years (4 in the treatment arm and 8 in the control arm) and 21 (21%) adults in the follow‐up study at age 20 years (10 in the treatment arm and 11 in the control arm)
Funding: Dutch Foundation for Research on Prevention (Praeventiefonds Project 28‐1145), the Netherlands

Participants

Location: Department of Obstetrics and Gynaecology and Department of Neonatology, Wilhelmina Gasthuis, University of Amsterdam, Amsterdam, the Netherlands.
Timeframe: April 1974‐April 1977
Eligibility criteria: women with preterm labour in whom it was possible to delay delivery by at least 12 h
Gestational age range: 26‐32 weeks. Exclusion criteria: no contraindications to the use of corticosteroids or orciprenaline (insulin‐treated diabetes, hyperthyroidism, infection, severe hypertension, cardiac disease, marked fetal growth retardation or fetal distress)
Total recruited: 101 women and 123 infants; 50 women and 65 infants in the treatment arm and 51 women and 58 infants in the control arm

Interventions

The treatment group received 8 mg betamethasone phosphate and 6 mg betamethasone acetate IM repeated after 24 h.
The control group received an identical placebo.

All women received orciprenaline infusion and bed‐rest until 32 weeks.

Outcomes

Maternal outcomes (death, chorioamnionitis, maternal infections, fever after trial entry requiring antibiotics, intrapartum fever requiring antibiotics, postnatal fever, admission to ICU, side effects of therapy), fetal/neonatal outcomes (fetal death, neonatal death, RDS, IVH, birthweight, Apgar score < 7), childhood outcomes (weight, height, head circumference, lung function, visual impairment, hearing impairment, intellectual impairment, cerebral palsy, behavioural/learning difficulties) and adulthood outcomes were reported (weight, height, head circumference, blood pressure, intellectual impairment, age at puberty)

Notes

Initial study report included a third arm of women (n = 133) and infants (n = 164) who had been excluded from randomisation because they were: 1. already in labour (n = 80) and could not be prolonged for at least 12 h or were already 33 weeks' gestation, or; 2. (n = 53) contra‐indicated for corticosteroids, or; 3. wrongly excluded (n = 5). These women and infants are not included in the review.

Two perinatal deaths in the corticosteroid treatment arm were excluded for: 1. intrauterine fetal death due to solutio placentae, and 2. death due to prolapsed umbilical cord. These deaths have been included in the analyses.

Infections in infants are listed in Table 6 of the Schutte 1979 original report. There are deaths associated with these infections, and it is not clear when these infections or deaths occurred, or if they have been included in the reported numbers for neonatal or perinatal deaths.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Low risk

Coded drug ampoules prepared by pharmacist

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Trial described as double blind, with pharmacist preparing identical treatment and control ampoules

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Staff were blind to treatment group

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

2 perinatal deaths in the corticosteroids group were excluded. Data for infant infections specify additional deaths, and it is unclear whether or not these deaths are counted in the overall total for perinatal deaths. The inclusion of these deaths will not change the overall conclusions of meta‐analysis in favour of corticosteroid use

Selective reporting (reporting bias)

Low risk

Primary outcome of the trial was RDS; this and other important outcomes are reported

Other bias

Unclear risk

We are unclear as to the impact of exclusions on results, especially for the outcome of perinatal deaths.

Shanks 2010

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: not stated other than "randomly assigned"

Stratification: not stated
Placebo: no
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: 7 (22%) women (3 in the study group and 4 in the control group) delivered within 7 d of their initial testing for fetal lung maturity and were excluded from the analysis
Funding: supported in part by a Clinical and Translational Science Award, and by a grant from the National Centre for Research Resources, a component of the National Institute of Health and NIH Roadmap for Medical Research

Participants

Location: Barnes‐Jewish Hospital, St Louis, Missouri, USA
Timeframe: May 2003‐May 2008
Eligibility criteria: singleton gestation, between 34 + 0 and 36 + 6 weeks' gestation, immature TDx‐FLM‐II test (< 45 mg/g) (this test measures surfactant to albumin ratio) after clinically indicated amniocentesis to test for fetal lung maturity.
Gestational age range: 34 + 0 ‐36 + 6 weeks' gestation
Exclusion criteria: multiple gestations, ruptured membranes, uncertain gestational ages, previous steroid treatment in current pregnancy, delivery before completing the steroid course, those unwilling or unable to comply with study protocol
Total recruited: 32 women and infants; 13 women and infants in the treatment arm and 19 women and infants in the control arm

Interventions

The treatment group received either 2 doses of betamethasone 12 mg IM 24 h apart, or 4 doses of dexamethasone 6 mg IM 12 h apart.

The control group received no treatment.

Outcomes

Maternal outcomes (side effects of therapy in women) and fetal/neonatal outcomes (need for mechanical ventilation/CPAP, admission to NICU)

Notes

This study was stopped early due to difficulties in participant recruitment

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Randomly assigned" not further described

Allocation concealment (selection bias)

Unclear risk

"Sealed envelopes" not further described

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Control group received no treatment so blinding of participants and study personnel would not have been possible

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No mention is made of blinding of outcome assessors

Incomplete outcome data (attrition bias)
All outcomes

High risk

7 (22%) women (3 in the study group and 4 in the control group) delivered within 7 d of their initial testing for fetal lung maturity and were excluded from the analysis. No intention‐to‐treat analysis

Selective reporting (reporting bias)

High risk

Hyaline membrane disease is listed as an outcome, but not reported

Other bias

High risk

This study was stopped early due to difficulties in patient recruitment

Silver 1996

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: computer‐generated randomisation sequence used Pharmacy provided identical syringes labelled with the woman's study number. Stratification: none stated
Placebo: yes, normal saline
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: 124 women initially recruited, of whom 49 (40%) remained undelivered after 29 weeks and were not included in the review
Funding: not stated

Participants

Location: Northwestern University Medical School, Chicago, Illinois, USA
Timeframe: April 1990‐June 1994
Eligibility criteria: women at risk of delivery between 24‐29 weeks
Gestational age range: 24‐29 weeks
Exclusion criteria: infection, maternal or fetal indications for urgent delivery
Total recruited: 75 women and 96 infants; 39 women and 54 infants in the treatment arm and 36 women and 42 infants in the control arm

Interventions

The treatment group received 4 doses of 5 mg dexamethasone IM 12 h apart, repeated weekly if the women remained undelivered.
The control group received placebo.

All infants born < 30 weeks received prophylactic surfactant at birth.

Outcomes

Maternal outcomes (chorioamnionitis, endometritis) and fetal/neonatal outcomes reported (neonatal death, RDS, chronic lung disease, IVH, small‐for‐gestational age, birthweight, necrotising enterocolitis)

Notes

Those women undelivered after 29 weeks were eligible for corticosteroid outside the study protocol. These women and their infants are not included in the review as it was not possible to separate out control women who subsequently received corticosteroids

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation sequence used

Allocation concealment (selection bias)

Low risk

Pharmacy provided identical syringes labelled with the woman's study number.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"Clinical personnel and the patient were effectively blinded to study group assignment"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The severity of RDS, and diagnosis of IVH were "confirmed independently by chart reviews conducted by 1 of the authors blinded to study group assignment"

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

49 (40%) of the 124 women initially recruited, remained undelivered after 29 weeks and were not included in the review.

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Taeusch 1979

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Coded drug boxes used

Stratification: yes, by gestational age at entry
Placebo: yes, normal saline
Sample size calculation: yes
Intention‐to‐treat analyses: no
Losses to follow‐up: yes, data not available for maternal outcomes on 4 women (2 in each treatment arm)
Funding: not stated

Participants

Location: 2 hospitals in Boston, USA
Timeframe: January 1975‐March 1977
Eligibility criteria: women with preterm labour, PROM or with cervical dilatation < 5 cm at 33 weeks or less and women with an L/S ratio < 2 if > 33 weeks or who had a previous infant with RDS
Gestational age range: not stated
Exclusion criteria: indication for immediate delivery, obstetrician objection, pre‐eclampsia, previously received corticosteroids
Total recruited: 122 women and 127 infants recruited; 39 women and 54 infants randomised to the treatment arm and 36 women and 42 infants randomised to the control arm

Interventions

The treatment group received 6 doses of 4 mg dexamethasone phosphate IM 8 h apart.
The control group received placebo.

Outcomes

Maternal outcomes (endometritis, fever after trial entry requiring antibiotics) and fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, chronic lung disease, IVH, proven neonatal infection while in NICU)

Notes

Study authors contacted for further information but there was no reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Coded drug boxes were used, but it is not clear how they were coded, e.g. if they were sequentially numbered.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is likely that participants were blinded due to the use of an identical looking placebo. Blinding of study personnel was not described.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Diagnosis of RDS was made prior to breaking the treatment code.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Data not available for maternal outcomes on 4 (3%) women (2 in each treatment arm) with no explanation given.

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

Insufficient information to asses if other sources of bias exist.

Teramo 1980

Study characteristics

Methods

Type of study: RCT
Method of treatment allocation: method of randomisation not stated. Coded drug boxes used. Stratification: none stated
Placebo: yes, normal saline
Sample size calculation: no
Intention‐to‐treat analyses: yes
Losses to follow‐up: no
Funding: not stated

Participants

Location: University of Helsinki, Finland
Timeframe: not stated in manuscript, the study is coded as 1980s for the review
Eligibility criteria: women with preterm labour and cervical dilatation < 4 cm without progression of labour upon initial observation of up to 12 h
Gestational age range: 28 ‐35 weeks
Exclusion criteria: pre‐eclampsia, diabetes
Total recruited: 74 women and 80 infants; 36 women and 38 infants in the treatment arm and 38 women and 42 infants in the control arm

Interventions

The treatment group received 2 doses of 12 mg betamethasone IM 24 h apart.
The control group received placebo.

Outcomes

Fetal/neonatal outcomes reported (RDS, HPA axis function)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomisation not stated

Allocation concealment (selection bias)

Unclear risk

Coded drug boxes were used but it is not clear how they were coded, e.g. if they were sequentially numbered.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

It is likely that participants were blinded due to the use of a placebo "similar in appearance" to the corticosteroid. Blinding of study personnel was not described other than "ampoules were administered to the patients using the double‐blind principle".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessors was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses to follow‐up or exclusions stated

Selective reporting (reporting bias)

Low risk

Study protocol not available, but appears to report on all pre‐specified outcomes

Other bias

Unclear risk

The study was discontinued early because the overall incidence of RDS was too low for any meaningful conclusions concerning the efficacy of prevention.

CPAP: continuous positive airways pressure
GDM: gestational diabetes mellitus
HPA: hypothalamic‐pituitary‐adrenal
ICU: intensive care unit
IM: intramuscular
IUGR: Iintrauterine growth restriction
IV: intravenous
IVH: intraventricular haemorrhage
LMP: last menstrual period
NICU: neonatal intensive care unit
PIH: pregnancy induced hypertension
PROM: premature rupture of membranes
PPROM: prolonged premature rupture of membranes
RCT: randomised controlled trial
RDS: respiratory distress syndrome
Rh: Rhesus
SD: standard deviation

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Abuhamad 1999

This abstract compares TRH + betamethasone with betamethasone + placebo.

Althabe 2015

This is a trial of strategies to optimise use of corticosteroids.

Asnafei 2004

This study is quasi‐experimental.

Butterfill 1979

Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately.

Dola 1997

This abstract compares TRH + betamethasone with betamethasone + placebo.

Egerman 1998

This trial compares oral vs IM dexamethasone in the prevention of RDS. It does not meet our entry criteria for inclusion of studies for the review.

Garite 1981

This trial compares a policy of corticosteroid therapy followed by elective delivery with a policy of withholding corticosteroids and awaiting delivery so the independent effect of the 2 co‐interventions cannot be evaluated separately.

Grgic 2003

Not a randomised trial. Outcomes for women who received steroids were compared with those that did not. Information obtained from translation sheet. Original article in Bosnian

Halac 1990

Not a randomised trial. Women were allocated to placebo if they were expected to deliver within 24 h and to betamethasone if labour was not expected within 24 h.

Iams 1985

Corticosteroid therapy (hydrocortisone) and co‐intervention of elective delivery was compared to expectant management in PROM. The independent effect of the 2 co‐interventions cannot be evaluated separately.

Khandelwal 2012

Compared different doses of corticosteroid: 12‐hourly vs 24‐hourly. The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015.

Koivisto 2007

The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015.

Kuhn 1982

Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately.

Kurtzman 2008

The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015.

Liu 2006

Quasi‐randomised study that allocated women according to the in‐patient sequence. Compared the effect of dexamethasone combined with vitamin K, dexamethasone alone and no dexamethasone or vitamin K on periventricular/intraventricular haemorrhage.

Magee 1997

This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate.

Maksic 2008

This study appears to be an observational study of 163 premature infants, 80 of whom were exposed to antenatal corticosteroids, and 83 of whom were not.

McEvoy 2010

This trial compares repeat dose corticosteroids and is eligible for inclusion a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015.

Minoui 1998

This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate.

Morales 1986

Quasi‐randomised using medical record number.

Morrison 1978

This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions and the fact that it was possibly quasi‐randomised.

Mulder 1997

This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate.

Papageorgiou 1979

This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions. Of 146 babies included in the study, the paper only reports outcomes for 61.

Romejko‐Wolniewicz 2013

This is a head‐to‐head trial of 2 different regimens and is eligible for the Cochrane review entitled 'Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth' Brownfoot 2013.

Rotmensch 1999

This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate.

Schmidt 1984

This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions. The paper only reports results from 92 of 144 randomised mothers and 97 of 149 randomised babies.

Simpson 1985

Quasi‐randomised study. Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately.

Whitt 1976

This trial compares IM betamethasone with IV cortisol. It does not meet our entry criteria for inclusion of studies for the review.

IM: intramuscular
IV: intravenous
PROM: premature rupture of membranes
RDS: respiratory distress syndrome
TRH: thyrotropin‐releasing hormone
vs: versus

Data and analyses

Open in table viewer
Comparison 1. Corticosteroids versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Maternal death Show forest plot

5

3392

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.06, 15.50]

Analysis 1.1

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death

1.2 Chorioamnionitis Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

Analysis 1.2

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis

1.3 Endometritis Show forest plot

10

4030

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.87, 1.63]

Analysis 1.3

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis

1.4 Perinatal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

Analysis 1.4

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths

1.5 Neonatal deaths Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 1.5

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths

1.6 Fetal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 1.6

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths

1.7 Respiratory distress syndrome Show forest plot

28

7764

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.56, 0.77]

Analysis 1.7

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome

1.8 Moderate/severe respiratory distress syndrome Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

Analysis 1.8

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome

1.9 Chronic lung disease Show forest plot

6

818

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.42, 1.79]

Analysis 1.9

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease

1.10 Intraventricular haemorrhage Show forest plot

16

6093

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.40, 0.76]

Analysis 1.10

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage

1.11 Mean birthweight (g) Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

Analysis 1.11

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g)

1.12 Death in childhood Show forest plot

4

1010

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.36, 1.27]

Analysis 1.12

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood

1.13 Neurodevelopmental delay in childhood Show forest plot

1

82

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.14, 2.98]

Analysis 1.13

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood

1.14 Death into adulthood Show forest plot

1

988

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.56, 1.81]

Analysis 1.14

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood

1.15 Fever in women after trial entry requiring the use of antibiotics Show forest plot

4

481

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.43, 2.06]

Analysis 1.15

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics

1.16 Intrapartum fever in woman requiring the use of antibiotics Show forest plot

2

319

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.09, 4.89]

Analysis 1.16

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics

1.17 Side effects of therapy in women Show forest plot

6

3572

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.82]

Analysis 1.17

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women

1.18 Admission into adult intensive care unit Show forest plot

2

319

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.26, 2.05]

Analysis 1.18

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit

1.19 Hypertension Show forest plot

1

220

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.36, 2.76]

Analysis 1.19

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension

1.20 Postnatal fever in woman Show forest plot

5

1323

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.64, 1.33]

Analysis 1.20

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman

1.21 Glucose intolerance Show forest plot

1

123

Risk Ratio (M‐H, Fixed, 95% CI)

2.71 [1.14, 6.46]

Analysis 1.21

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance

1.22 Necrotising enterocolitis Show forest plot

10

4702

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.32, 0.78]

Analysis 1.22

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis

1.23 Systemic infection in the first 48 hours of life Show forest plot

8

1753

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.41, 0.88]

Analysis 1.23

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life

1.24 Proven infection while in the neonatal intensive care unit Show forest plot

13

5707

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.55, 1.08]

Analysis 1.24

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit

1.25 Need for mechanical ventilation/CPAP Show forest plot

9

1368

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.56, 0.84]

Analysis 1.25

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP

1.26 Mean duration of mechanical ventilation/CPAP (days) Show forest plot

3

471

Mean Difference (IV, Random, 95% CI)

‐1.91 [‐4.59, 0.76]

Analysis 1.26

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days)

1.27 Mean duration of oxygen supplementation (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.27

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days)

1.28 Surfactant use Show forest plot

5

3556

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.51, 0.90]

Analysis 1.28

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use

1.29 Air leak syndrome Show forest plot

2

2965

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.32, 1.80]

Analysis 1.29

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome

1.30 Apgar < 7 at 5 minutes Show forest plot

10

2419

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.67, 0.98]

Analysis 1.30

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes

1.31 Mean interval between trial entry and birth (days) Show forest plot

3

1513

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐1.86, 2.32]

Analysis 1.31

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days)

1.32 Small‐for‐gestational age Show forest plot

5

3478

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.96, 1.28]

Analysis 1.32

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age

1.33 Mean infant HPA axis function (cortisol) Show forest plot

1

27

Mean Difference (IV, Fixed, 95% CI)

3.94 [‐3.12, 11.00]

Analysis 1.33

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol)

1.33.1 In babies born < 24 hours after 1st dose

1

6

Mean Difference (IV, Fixed, 95% CI)

9.00 [‐11.93, 29.93]

1.33.2 In babies born 24‐48 hours after 1st dose

1

10

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐8.68, 8.68]

1.33.3 In babies born > 48 hours after 1st dose

1

11

Mean Difference (IV, Fixed, 95% CI)

13.00 [‐1.90, 27.90]

1.34 Admission to neonatal intensive care unit Show forest plot

7

3803

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.84, 0.97]

Analysis 1.34

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit

1.35 Developmental delay in childhood Show forest plot

2

518

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.24, 1.00]

Analysis 1.35

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood

1.36 Cerebral palsy in childhood Show forest plot

5

904

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.34, 1.03]

Analysis 1.36

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood

1.37 Mean childhood weight (kg) Show forest plot

2

333

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.39, 1.00]

Analysis 1.37

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg)

1.37.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐0.32, 1.12]

1.37.2 Schutte (females)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐2.40 [‐6.55, 1.75]

1.37.3 Schutte (males)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐3.88, 3.68]

1.38 Mean childhood height (cm) Show forest plot

2

334

Mean Difference (IV, Fixed, 95% CI)

1.02 [‐0.26, 2.29]

Analysis 1.38

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm)

1.38.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

1.00 [‐0.39, 2.39]

1.38.2 Schutte (females)

1

39

Mean Difference (IV, Fixed, 95% CI)

1.70 [‐3.08, 6.48]

1.38.3 Schutte (males)

1

45

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐3.79, 4.99]

1.39 Mean childhood head circumference (cm) Show forest plot

2

328

Mean Difference (IV, Fixed, 95% CI)

0.27 [‐0.08, 0.63]

Analysis 1.39

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm)

1.39.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.11, 0.71]

1.39.2 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐1.05, 0.85]

1.39.3 Schutte (males)

1

42

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐0.51, 1.71]

1.40 Mean childhood VC (% predicted) Show forest plot

2

150

Mean Difference (IV, Fixed, 95% CI)

‐1.68 [‐5.12, 1.75]

Analysis 1.40

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted)

1.40.1 Liggins

1

75

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐5.12, 6.52]

1.40.2 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐2.60 [‐8.65, 3.45]

1.40.3 Schutte (males)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐3.30 [‐9.27, 2.67]

1.41 Mean childhood FEV1 (% predicted) Show forest plot

1

75

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐10.13, 0.67]

Analysis 1.41

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted)

1.41.1 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐2.50 [‐11.24, 6.24]

1.41.2 Schutte (males)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐6.10 [‐12.96, 0.76]

1.42 Mean childhood FEV1/VC Show forest plot

2

150

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐3.63, 1.76]

Analysis 1.42

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC

1.42.1 Liggins

1

75

Mean Difference (IV, Random, 95% CI)

1.00 [‐2.57, 4.57]

1.42.2 Schutte (females)

1

36

Mean Difference (IV, Random, 95% CI)

0.00 [‐5.56, 5.56]

1.42.3 Schutte (males)

1

39

Mean Difference (IV, Random, 95% CI)

‐3.00 [‐6.14, 0.14]

1.43 Mean childhood systolic blood pressure (mmHg) Show forest plot

1

223

Mean Difference (IV, Fixed, 95% CI)

‐1.60 [‐4.06, 0.86]

Analysis 1.43

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg)

1.44 Visual impairment in childhood Show forest plot

2

166

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.24, 1.23]

Analysis 1.44

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood

1.45 Hearing impairment in childhood Show forest plot

2

166

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.04, 9.87]

Analysis 1.45

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood

1.46 Intellectual impairment in childhood Show forest plot

3

778

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.69]

Analysis 1.46

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood

1.47 Behavioural/learning difficulties in childhood Show forest plot

1

90

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.35, 2.09]

Analysis 1.47

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood

1.48 Mean adult insulin (log values) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.48

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values)

1.48.1 Fasting

1

435

Mean Difference (IV, Fixed, 95% CI)

0.08 [‐0.03, 0.19]

1.48.2 30 minutes following a 75 g oral glucose tolerance test

1

412

Mean Difference (IV, Fixed, 95% CI)

0.16 [0.04, 0.28]

1.48.3 120 minutes following a 75 g oral glucose tolerance test

1

428

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.27, 0.07]

1.49 Mean adult glucose (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.49

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L)

1.49.1 Fasting

1

432

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.09, 0.11]

1.49.2 30 minutes following a 75 g oral glucose tolerance test

1

413

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.14, 0.52]

1.49.3 120 minutes following a 75 g oral glucose tolerance test

1

410

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.52, ‐0.02]

1.50 Mean adult weight (kg) Show forest plot

2

538

Mean Difference (IV, Random, 95% CI)

‐0.83 [‐6.41, 4.76]

Analysis 1.50

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg)

1.50.1 Schutte (females)

1

37

Mean Difference (IV, Random, 95% CI)

‐6.00 [‐12.93, 0.93]

1.50.2 Schutte (males)

1

43

Mean Difference (IV, Random, 95% CI)

‐1.00 [‐9.91, 7.91]

1.50.3 Liggins

1

458

Mean Difference (IV, Random, 95% CI)

2.57 [‐0.72, 5.86]

1.51 Mean adult height (cm) Show forest plot

2

537

Mean Difference (IV, Fixed, 95% CI)

0.91 [‐0.28, 2.10]

Analysis 1.51

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm)

1.51.1 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐1.00 [‐5.37, 3.37]

1.51.2 Schutte (males)

1

43

Mean Difference (IV, Fixed, 95% CI)

3.00 [‐2.30, 8.30]

1.51.3 Liggins (females)

1

234

Mean Difference (IV, Fixed, 95% CI)

1.17 [‐0.65, 2.99]

1.51.4 Liggins (males)

1

224

Mean Difference (IV, Fixed, 95% CI)

0.75 [‐1.03, 2.53]

1.52 Mean adult head circumference (cm) Show forest plot

2

537

Mean Difference (IV, Fixed, 95% CI)

0.03 [‐0.33, 0.38]

Analysis 1.52

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm)

1.52.1 Schutte (females)

1

37

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐1.03, 1.03]

1.52.2 Schutte (males)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.37, 0.97]

1.52.3 Liggins

1

458

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.34, 0.46]

1.53 Mean adult skinfold thickness (log values) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.53

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values)

1.53.1 Triceps

1

456

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.11, 0.07]

1.53.2 Biceps

1

456

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.11, 0.09]

1.53.3 Subscapular

1

441

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.08, 0.10]

1.53.4 Suprailiac

1

452

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.10]

1.54 Mean adult systolic blood pressure (mmHg) Show forest plot

2

545

Mean Difference (IV, Random, 95% CI)

‐1.53 [‐4.50, 1.44]

Analysis 1.54

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg)

1.54.1 Schutte (females)

1

38

Mean Difference (IV, Random, 95% CI)

‐4.00 [‐9.12, 1.12]

1.54.2 Schutte (males)

1

52

Mean Difference (IV, Random, 95% CI)

‐3.00 [‐7.17, 1.17]

1.54.3 Liggins

1

455

Mean Difference (IV, Random, 95% CI)

0.55 [‐1.88, 2.98]

1.55 Mean adult HPA axis function (mean log fasting cortisol) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.55

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)

1.56 Mean cholesterol in adulthood (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.56

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L)

1.57 Mean age at puberty (years) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.57

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years)

1.57.1 Schutte (females)

1

38

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.94, 0.94]

1.58 Educational achievement by adulthood (university or polytechnic education) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.58

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education)

1.59 Visual impairment in adulthood Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.59

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood

1.60 Hearing impairment in adulthood Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.60

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood

1.61 Intellectual impairment in adulthood Show forest plot

2

273

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.01, 4.95]

Analysis 1.61

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood

1.62 Mean adult FVC (% predicted) Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐3.16, 1.76]

Analysis 1.62

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted)

1.63 Mean adult FEV1 (% predicted) Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐2.31, 3.11]

Analysis 1.63

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted)

1.64 Mean adult FEV1/FVC Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.01, 0.03]

Analysis 1.64

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC

1.65 Mean adult PEF Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

2.20 [‐0.77, 5.17]

Analysis 1.65

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF

1.66 Mean adult F50 Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

3.00 [‐1.57, 7.57]

Analysis 1.66

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50

1.67 Mean adult F25 Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐3.82, 4.62]

Analysis 1.67

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25

1.68 Mean adult FEF 25%‐75% Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

2.20 [‐2.10, 6.50]

Analysis 1.68

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75%

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75%

1.69 FEV1/FVC < 70% Show forest plot

1

383

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.49, 1.57]

Analysis 1.69

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70%

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70%

1.70 Asthma diagnosed by Doctor in lifetime Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 1.70

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime

1.71 Wheezing in last 12 months Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.84, 1.35]

Analysis 1.71

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months

1.72 Current Asthma Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.74, 1.48]

Analysis 1.72

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma

1.73 Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis) Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.69, 2.59]

Analysis 1.73

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis)

1.74 Spontaneous pneumothorax Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.07, 17.66]

Analysis 1.74

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax

1.75 Shortness of breath at anytime in the last 12 months Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.80, 1.31]

Analysis 1.75

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months

1.76 Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.04, 0.04]

Analysis 1.76

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density

1.77 Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.01, 0.01]

Analysis 1.77

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density

1.78 Mean adult total body BMC (grams) bone mineral content Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

18.00 [‐151.30, 187.30]

Analysis 1.78

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content

1.79 Mean adult total body aBMD (g/cm3) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.03, 0.03]

Analysis 1.79

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density

1.80 Mean adult femoral neck aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.03, 0.07]

Analysis 1.80

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density

1.81 Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.02, 0.06]

Analysis 1.81

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density

1.82 Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.04, 0.06]

Analysis 1.82

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density

1.83 Mean total proximal femur aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.03, 0.07]

Analysis 1.83

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density

1.84 Mean length of antenatal hospitalisation (days) Show forest plot

1

218

Mean Difference (IV, Fixed, 95% CI)

0.50 [‐1.40, 2.40]

Analysis 1.84

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days)

1.85 Mean length of postnatal hospitalisation (days) Show forest plot

1

218

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐1.72, 1.72]

Analysis 1.85

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days)

1.86 Mean length of neonatal hospitalisation (days) Show forest plot

5

788

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.51, 0.87]

Analysis 1.86

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days)

Open in table viewer
Comparison 2. Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Chorioamnionitis ‐ single or multiple pregnancy Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

Analysis 2.1

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy

2.1.1 In women delivering singleton pregnancies

7

4682

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.56, 1.01]

2.1.2 In women delivering multiple pregnancies

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.04, 4.49]

2.1.3 Mixed population

8

790

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.70, 1.57]

2.2 Perinatal death ‐ single or multiple pregnancy Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.59, 0.89]

Analysis 2.2

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy

2.2.1 In babies born from singleton pregnancies

6

5182

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.54, 1.05]

2.2.2 In babies born from multiple pregnancies

2

252

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.37, 1.47]

2.2.3 Mixed population

9

1295

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.49, 0.94]

2.3 Neonatal death ‐ single or multiple pregnancy Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 2.3

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy

2.3.1 In babies born from singleton pregnancies

9

5335

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.61, 0.92]

2.3.2 In babies born from multiple pregnancies

2

236

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.39, 1.61]

2.3.3 Mixed population

13

1617

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.46, 0.78]

2.4 Fetal death ‐ single or multiple pregnancy Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.73, 1.29]

Analysis 2.4

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy

2.4.1 In babies born from singleton pregnancies

6

5182

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.75, 1.45]

2.4.2 In babies born from multiple pregnancies

2

252

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.20, 1.40]

2.4.3 Mixed population

9

1295

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.50, 1.99]

2.5 Respiratory distress syndrome ‐ single or multiple pregnancy Show forest plot

28

7762

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.59, 0.78]

Analysis 2.5

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy

2.5.1 In babies born from singleton pregnancies

15

6081

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.50, 0.77]

2.5.2 In babies born from multiple pregnancies

4

320

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.67, 1.22]

2.5.3 Mixed population

13

1361

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.53, 0.89]

2.6 IVH ‐ single or multiple pregnancy Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

Analysis 2.6

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy

2.6.1 In babies born from singleton pregnancies

8

4782

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.36, 0.75]

2.6.2 In babies born from multiple pregnancies

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.07, 2.06]

2.6.3 Mixed population

8

1174

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.44, 0.81]

2.7 Birthweight ‐ single or multiple pregnancy Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐17.61 [‐39.95, 4.74]

Analysis 2.7

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy

2.7.1 In babies born from singleton pregnancy

9

4948

Mean Difference (IV, Fixed, 95% CI)

‐24.12 [‐48.27, 0.03]

2.7.2 In babies born from multiple pregnancies

1

150

Mean Difference (IV, Fixed, 95% CI)

82.36 [‐146.23, 310.95]

2.7.3 Mixed population

7

1084

Mean Difference (IV, Fixed, 95% CI)

16.77 [‐44.16, 77.69]

Open in table viewer
Comparison 3. Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Chorioamnionitis ‐ intact or ruptured membranes Show forest plot

15

5517

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.67, 1.07]

Analysis 3.1

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes

3.1.1 In women with intact membranes at 1st dose

5

1437

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.50, 1.40]

3.1.2 In women with ruptured membranes at 1st dose

7

959

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.69, 1.40]

3.1.3 Not reported or mixed population

4

3121

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.47, 1.06]

3.2 Endometritis ‐ intact or ruptured membranes Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.80, 1.80]

Analysis 3.2

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes

3.2.1 In women with intact membranes at 1st dose

2

289

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.37, 4.01]

3.2.2 In women with ruptured membranes at 1st dose

4

477

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.35, 2.97]

3.2.3 Not reported or mixed population

5

3264

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.81, 2.13]

3.3 Perinatal death ‐ intact or ruptured membranes Show forest plot

15

6700

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.60, 0.90]

Analysis 3.3

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes

3.3.1 In babies born from pregnancies with intact membranes at 1st dose

4

1332

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.70, 1.08]

3.3.2 In babies born from pregnancies with ruptured membranes at 1st dose

4

733

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.39, 0.90]

3.3.3 Not reported or mixed population

8

4635

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.49, 1.03]

3.4 Neonatal deaths ‐ intact or ruptured membranes Show forest plot

22

7163

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 3.4

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes

3.4.1 In babies born from pregnancies with intact membranes at 1st dose

4

1236

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.58, 1.03]

3.4.2 In babies born from pregnancies with ruptured membranes at 1st dose

8

1024

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.46, 0.83]

3.4.3 Not reported or mixed population

11

4903

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.53, 0.88]

3.5 Fetal death ‐ intact or ruptured membranes Show forest plot

15

6634

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.26]

Analysis 3.5

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes

3.5.1 In babies born from pregnancies with intact membranes at 1st dose

4

1332

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.73, 1.64]

3.5.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

790

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.46, 1.61]

3.5.3 Not reported or mixed population

7

4512

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.44, 1.35]

3.6 RDS ‐ intact or ruptured membranes Show forest plot

28

7738

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.56, 0.76]

Analysis 3.6

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes

3.6.1 In babies born from pregnancies with intact membranes at 1st dose

6

1721

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.50, 0.80]

3.6.2 In babies born from pregnancies with ruptured membranes at 1st dose

12

1129

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.55, 0.90]

3.6.3 Not reported or mixed population

14

4888

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.46, 0.81]

3.7 IVH ‐ intact or ruptured membranes Show forest plot

15

5868

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

Analysis 3.7

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes

3.7.1 In babies born from pregnancies with intact membranes at 1st dose

5

1394

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.35, 0.72]

3.7.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

895

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.28, 0.79]

3.7.3 Not reported or mixed population

6

3579

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.49, 1.07]

3.8 Birthweight ‐ intact or ruptured membranes Show forest plot

16

6153

Mean Difference (IV, Fixed, 95% CI)

‐19.52 [‐41.81, 2.78]

Analysis 3.8

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes

3.8.1 In babies born from pregnancies with intact membranes at 1st dose

4

1301

Mean Difference (IV, Fixed, 95% CI)

‐30.27 [‐100.43, 39.89]

3.8.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

835

Mean Difference (IV, Fixed, 95% CI)

‐49.72 [‐113.91, 14.46]

3.8.3 Not reported or mixed population

8

4017

Mean Difference (IV, Fixed, 95% CI)

‐13.44 [‐38.71, 11.83]

Open in table viewer
Comparison 4. Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 RDS Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

Analysis 4.1

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS

4.1.1 Hypertension syndrome

5

382

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.35, 0.72]

4.1.2 No hypertension syndrome or hypertension syndromes excluded

9

2660

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.47, 0.71]

4.1.3 Hypertension not reported separately

18

4722

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.66, 0.85]

4.2 Perinatal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.60, 0.92]

Analysis 4.2

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths

4.2.1 Hypertension syndrome

2

313

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.42, 2.10]

4.2.2 No hypertension syndrome or hypertension syndromes excluded

3

1394

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.39, 1.29]

4.2.3 Hypertension not reported separately

11

5022

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.52, 0.93]

4.3 Fetal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 4.3

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths

4.3.1 Women with hypertension syndrome

3

331

Risk Ratio (M‐H, Fixed, 95% CI)

1.73 [0.91, 3.28]

4.3.2 No hypertension syndrome or hypertension syndromes excluded

4

1644

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.49, 1.08]

4.3.3 Hypertension not reported separately

10

4754

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.67, 1.98]

4.4 Neonatal deaths Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 4.4

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths

4.4.1 Hypertension syndrome

2

278

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.87]

4.4.2 No hypertension syndrome or hypertension syndromes excluded

3

1306

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.61, 1.09]

4.4.3 Hypertension not reported separately

18

5604

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.54, 0.82]

Open in table viewer
Comparison 5. Corticosteroids versus placebo or no treatment ‐ type of steroid

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Chorioamnionitis ‐ type of steroid Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

Analysis 5.1

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid

5.1.1 In women treated with dexamethasone

5

769

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.89, 2.05]

5.1.2 In women treated with betamethasone

10

4777

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.50, 0.90]

5.2 Endometritis ‐ type of steroid Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.81, 1.80]

Analysis 5.2

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid

5.2.1 In women treated with dexamethasone

4

536

Risk Ratio (M‐H, Random, 95% CI)

1.71 [0.86, 3.43]

5.2.2 In women treated with betamethasone

6

3494

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.63, 1.45]

5.3 Perinatal death ‐ type of steroid Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

Analysis 5.3

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid

5.3.1 In babies treated with dexamethasone

5

1420

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.46, 1.11]

5.3.2 In babies treated with betamethasone

10

5309

Risk Ratio (M‐H, Random, 95% CI)

0.73 [0.56, 0.94]

5.4 Neonatal deaths by steroid type Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 5.4

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type

5.4.1 In babies treated with dexamethasone

6

1468

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.55, 0.94]

5.4.2 In babies treated with betamethasone

16

5720

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.55, 0.83]

5.5 Fetal death ‐ type of steroid Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 5.5

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid

5.5.1 In babies treated with dexamethasone

5

1420

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.48, 1.60]

5.5.2 In babies treated with betamethasone

10

5309

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.73, 1.39]

5.6 Respiratory distress syndrome ‐ type of steroid Show forest plot

28

7764

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.56, 0.77]

Analysis 5.6

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid

5.6.1 In babies treated with dexamethasone

7

1651

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.61, 0.98]

5.6.2 In babies treated with betamethasone

20

6095

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.50, 0.73]

5.6.3 Steroid type not reported

1

18

Risk Ratio (M‐H, Random, 95% CI)

1.62 [0.08, 34.66]

5.7 IVH ‐ type of steroid Show forest plot

16

6093

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.40, 0.76]

Analysis 5.7

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid

5.7.1 In babies treated with dexamethasone

6

897

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.18, 1.26]

5.7.2 In babies treated with betamethasone

10

5196

Risk Ratio (M‐H, Random, 95% CI)

0.53 [0.40, 0.72]

5.8 Birthweight ‐ type of steroid Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

Analysis 5.8

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid

5.8.1 In babies treated with dexamethasone

4

686

Mean Difference (IV, Fixed, 95% CI)

‐17.04 [‐75.48, 41.41]

5.8.2 In babies treated with betamethasone

12

5496

Mean Difference (IV, Fixed, 95% CI)

‐18.71 [‐42.92, 5.50]

5.9 Moderate/severe respiratory distress syndrome ‐ type of steroid Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

Analysis 5.9

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid

5.9.1 Dexamethasone

2

219

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.46, 1.44]

5.9.2 Betamethasone

4

1467

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.27, 0.90]

5.10 Chronic lung disease ‐ type of steroid Show forest plot

6

818

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.42, 1.79]

Analysis 5.10

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid

5.10.1 Dexamethasone

2

219

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.72, 1.90]

5.10.2 Betamethasone

4

599

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.26, 2.28]

Open in table viewer
Comparison 6. Corticosteroids versus placebo or no treatment ‐ decade of trial

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Chorioamnionitis ‐ decade of trial Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

Analysis 6.1

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial

6.1.1 In women from trials conducted in 1970s

2

1237

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.46, 1.17]

6.1.2 In women from trials conducted in 1980s

3

276

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.25, 1.01]

6.1.3 In women from trials conducted in 1990s

6

755

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.80, 1.74]

6.1.4 in women from trials conducted in the 2000's

2

257

Risk Ratio (M‐H, Fixed, 95% CI)

2.02 [0.59, 6.95]

6.1.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.35, 1.07]

6.2 Endometritis ‐ decade of trial Show forest plot

10

4030

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.87, 1.63]

Analysis 6.2

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial

6.2.1 In women from trials conducted in 1970s

2

219

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [0.81, 4.27]

6.2.2 In women from trials conducted in 1980s

1

71

Risk Ratio (M‐H, Fixed, 95% CI)

2.30 [0.88, 6.06]

6.2.3 In women from trials conducted in 1990s

4

574

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.53, 1.44]

6.2.4 In women from trials conducted in the 2000's

3

3166

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.69, 2.01]

6.3 Perinatal deaths ‐ decade of trial Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

Analysis 6.3

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial

6.3.1 In babies from trials conducted in 1970s

6

1994

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.50, 1.00]

6.3.2 In babies from trials conducted in 1980s

3

879

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.42]

6.3.3 In babies from trials conducted in 1990s

3

615

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.43, 0.93]

6.3.4 in babies from trials conducted in 2000's

2

414

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.31, 0.70]

6.3.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Random, 95% CI)

4.91 [0.24, 102.09]

6.4 Neonatal deaths decade of trial Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 6.4

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial

6.4.1 In babies from trials conducted in 1970s

7

1968

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.56, 0.92]

6.4.2 In babies from trials conducted in 1980s

6

1096

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.70, 1.37]

6.4.3 In babies from trials conducted in 1990s

5

758

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.36, 0.84]

6.4.4 In babies from trials conducted in 2000s

3

539

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.31, 0.64]

6.4.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

6.5 Fetal death ‐ decade of trial Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 6.5

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial

6.5.1 In babies from trials conducted in 1970s

6

1994

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.67, 1.34]

6.5.2 In babies from trials conducted in 1980s

3

879

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.52, 2.00]

6.5.3 In babies from trials conducted in 1990s

3

615

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.49, 2.36]

6.5.4 In babies from trials conducted in 2000's

2

414

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.19, 4.50]

6.5.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

6.6 RDS ‐ decade of trial Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

Analysis 6.6

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial

6.6.1 In babies from trials conducted in 1970s

7

1939

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.43, 0.69]

6.6.2 In babies from trials conducted in 1980s

7

1167

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.59, 0.88]

6.6.3 In babies from trials conducted in 1990s

7

798

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.65, 0.91]

6.6.4 In babies from trials conducted in 2000s

5

839

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.26, 0.59]

6.6.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.61, 1.04]

6.7 IVH ‐ decade of trial Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

Analysis 6.7

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial

6.7.1 In babies from trials conducted in 1970s

4

1646

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.85]

6.7.2 In babies from trials conducted in 1980s

2

238

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.39, 0.94]

6.7.3 In babies from trials conducted in 1990s

5

722

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.42, 0.87]

6.7.4 In babies from trials conducted in 2000s

3

466

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.15, 0.73]

6.7.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

6.8 Birthweight ‐ decade of trial Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

Analysis 6.8

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial

6.8.1 In babies from trials conducted in 1970s

4

1739

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐83.55, 64.47]

6.8.2 In babies from trials conducted in 1980s

3

280

Mean Difference (IV, Fixed, 95% CI)

‐19.60 [‐108.55, 69.35]

6.8.3 In babies from trials conducted in 1990s

4

569

Mean Difference (IV, Fixed, 95% CI)

‐33.13 [‐102.39, 36.13]

6.8.4 In babies from trials conducted in 2000s

3

573

Mean Difference (IV, Fixed, 95% CI)

‐20.77 [‐61.95, 20.41]

6.8.5 In trials in 2010s

2

3021

Mean Difference (IV, Fixed, 95% CI)

‐15.18 [‐48.66, 18.29]

Open in table viewer
Comparison 7. Corticosteroids versus placebo or no treatment ‐ weekly repeats

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Chorioamnionitis ‐ Protocol with weekly repeats Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

Analysis 7.1

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats

7.1.1 In women treated with single courses only

7

4659

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.61, 1.11]

7.1.2 In women treated with courses including weekly repeats

8

887

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.57, 1.25]

7.2 Endometritis ‐ protocol with weekly repeats Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.81, 1.80]

Analysis 7.2

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats

7.2.1 In women treated with single courses only

5

3450

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.66, 1.64]

7.2.2 In women treated with courses including weekly repeats

5

580

Risk Ratio (M‐H, Random, 95% CI)

1.46 [0.72, 2.95]

7.3 Perinatal death ‐ protocol with weekly repeats Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

Analysis 7.3

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats

7.3.1 In babies treated with single course only

11

6250

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.61, 0.99]

7.3.2 In babies treated with courses including weekly repeats

4

479

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.44, 0.97]

7.4 Neonatal death ‐ protocol with weekly repeats Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

Analysis 7.4

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats

7.4.1 In babies treated with single course only

14

6266

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.63, 0.95]

7.4.2 In babies treated with courses including weekly repeats

8

922

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.43, 0.72]

7.5 Fetal death ‐ protocol with weekly repeats Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

Analysis 7.5

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats

7.5.1 In babies treated with single course only

11

6250

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.68, 1.25]

7.5.2 In babies treated with courses including weekly repeats

4

479

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.64, 2.87]

7.6 RDS ‐ protocol with weekly repeats Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

Analysis 7.6

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats

7.6.1 In babies treated with single course only

19

6818

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.61, 0.79]

7.6.2 In babies treated with courses including weekly repeats

9

946

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.52, 0.72]

7.7 IVH‐ protocol with weekly repeats Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

Analysis 7.7

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats

7.7.1 In babies treated with single course only

9

5216

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.33, 0.76]

7.7.2 In babies treated with courses including weekly repeats

7

877

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.45, 0.78]

7.8 Birthweight ‐ protocol with weekly repeats Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

Analysis 7.8

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats

7.8.1 In babies treated with single course only

12

5773

Mean Difference (IV, Fixed, 95% CI)

‐18.24 [‐42.12, 5.65]

7.8.2 In babies treated with courses including weekly repeats

4

409

Mean Difference (IV, Fixed, 95% CI)

‐20.10 [‐83.79, 43.60]

7.9 Moderate/severe respiratory distress syndrome Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

Analysis 7.9

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome

7.9.1 Single course

3

1259

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.44, 0.83]

7.9.2 Weekly repeats

3

427

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.13, 1.32]

Open in table viewer
Comparison 8. Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Chorioamnionitis ‐ gestational age at trial entry Show forest plot

15

5506

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.65, 1.05]

Analysis 8.1

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry

8.1.1 Less than or equal to 35 weeks + 0 days

13

2304

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.70, 1.19]

8.1.2 Greater than or equal to 34 weeks + 0 days

3

3202

Risk Ratio (M‐H, Fixed, 95% CI)

0.57 [0.33, 0.99]

8.2 Perinatal death ‐ gestational age at trial entry Show forest plot

15

6687

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.59, 0.88]

Analysis 8.2

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry

8.2.1 Less than or equal to 35 weeks + 0 days

13

3391

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.58, 0.87]

8.2.2 Greater than or equal to 34 weeks + 0 days

3

3296

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.29, 3.67]

8.3 Neonatal death ‐ gestational age at trial engry Show forest plot

22

7146

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.57, 0.79]

Analysis 8.3

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry

8.3.1 Less than or equal to 35 weeks + 0 days

20

3855

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.57, 0.79]

8.3.2 Greater than or equal to 34 weeks + 0 days

3

3291

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.22, 3.07]

8.4 Fetal death ‐ gestational age at trial entry Show forest plot

15

6687

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.72, 1.27]

Analysis 8.4

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry

8.4.1 Less than or equal to 35 weeks + 0 days

13

3391

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.25]

8.4.2 Greater than or equal to 34 weeks + 0 days

3

3296

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.28, 9.37]

8.5 RDS‐ gestational age at trial entry Show forest plot

28

7722

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.60, 0.73]

Analysis 8.5

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry

8.5.1 Less than or equal to 35 weeks + 0 days

23

3939

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.58, 0.73]

8.5.2 Greater than or equal to 34 weeks + 0 days

6

3783

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.56, 0.91]

8.6 IVH ‐ gestational age at trial entry Show forest plot

16

6051

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.44, 0.70]

Analysis 8.6

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry

8.6.1 Less than or equal to 35 weeks + 0 days

13

2639

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.42, 0.68]

8.6.2 Greater than or equal to 34 weeks + 0 days

4

3412

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

8.7 Birthweight ‐ gestational age at trial entry Show forest plot

16

6140

Mean Difference (IV, Fixed, 95% CI)

‐17.45 [‐39.76, 4.86]

Analysis 8.7

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry

8.7.1 Less than or equal to 35 weeks + 0 days

11

2352

Mean Difference (IV, Fixed, 95% CI)

‐17.89 [‐63.14, 27.36]

8.7.2 Greater than or equal to 34 weeks + 0 days

6

3788

Mean Difference (IV, Fixed, 95% CI)

‐17.31 [‐42.96, 8.34]

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Figuras y tablas -
Figure 1

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

Figuras y tablas -
Figure 2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 Chorioamnionitis

Figuras y tablas -
Figure 3

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 Chorioamnionitis

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.4 Perinatal deaths

Figuras y tablas -
Figure 4

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.4 Perinatal deaths

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.5 Neonatal deaths

Figuras y tablas -
Figure 5

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.5 Neonatal deaths

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.6 Fetal deaths

Figuras y tablas -
Figure 6

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.6 Fetal deaths

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Respiratory distress syndrome

Figuras y tablas -
Figure 7

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Respiratory distress syndrome

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.10 Intraventricular haemorrhage

Figuras y tablas -
Figure 8

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.10 Intraventricular haemorrhage

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Mean birthweight (g)

Figuras y tablas -
Figure 9

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Mean birthweight (g)

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.25 Need for mechanical ventilation/CPAP

Figuras y tablas -
Figure 10

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.25 Need for mechanical ventilation/CPAP

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.30 Apgar < 7 at 5 minutes

Figuras y tablas -
Figure 11

Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.30 Apgar < 7 at 5 minutes

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death

Figuras y tablas -
Analysis 1.1

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis

Figuras y tablas -
Analysis 1.2

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis

Figuras y tablas -
Analysis 1.3

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths

Figuras y tablas -
Analysis 1.4

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths

Figuras y tablas -
Analysis 1.5

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths

Figuras y tablas -
Analysis 1.6

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome

Figuras y tablas -
Analysis 1.7

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome

Figuras y tablas -
Analysis 1.8

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease

Figuras y tablas -
Analysis 1.9

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage

Figuras y tablas -
Analysis 1.10

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g)

Figuras y tablas -
Analysis 1.11

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood

Figuras y tablas -
Analysis 1.12

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood

Figuras y tablas -
Analysis 1.13

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood

Figuras y tablas -
Analysis 1.14

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics

Figuras y tablas -
Analysis 1.15

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics

Figuras y tablas -
Analysis 1.16

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women

Figuras y tablas -
Analysis 1.17

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit

Figuras y tablas -
Analysis 1.18

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension

Figuras y tablas -
Analysis 1.19

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman

Figuras y tablas -
Analysis 1.20

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance

Figuras y tablas -
Analysis 1.21

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis

Figuras y tablas -
Analysis 1.22

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life

Figuras y tablas -
Analysis 1.23

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit

Figuras y tablas -
Analysis 1.24

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP

Figuras y tablas -
Analysis 1.25

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days)

Figuras y tablas -
Analysis 1.26

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days)

Figuras y tablas -
Analysis 1.27

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use

Figuras y tablas -
Analysis 1.28

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome

Figuras y tablas -
Analysis 1.29

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes

Figuras y tablas -
Analysis 1.30

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days)

Figuras y tablas -
Analysis 1.31

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age

Figuras y tablas -
Analysis 1.32

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol)

Figuras y tablas -
Analysis 1.33

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit

Figuras y tablas -
Analysis 1.34

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood

Figuras y tablas -
Analysis 1.35

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood

Figuras y tablas -
Analysis 1.36

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg)

Figuras y tablas -
Analysis 1.37

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm)

Figuras y tablas -
Analysis 1.38

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm)

Figuras y tablas -
Analysis 1.39

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted)

Figuras y tablas -
Analysis 1.40

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted)

Figuras y tablas -
Analysis 1.41

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC

Figuras y tablas -
Analysis 1.42

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg)

Figuras y tablas -
Analysis 1.43

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood

Figuras y tablas -
Analysis 1.44

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood

Figuras y tablas -
Analysis 1.45

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood

Figuras y tablas -
Analysis 1.46

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood

Figuras y tablas -
Analysis 1.47

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values)

Figuras y tablas -
Analysis 1.48

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L)

Figuras y tablas -
Analysis 1.49

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg)

Figuras y tablas -
Analysis 1.50

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm)

Figuras y tablas -
Analysis 1.51

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm)

Figuras y tablas -
Analysis 1.52

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values)

Figuras y tablas -
Analysis 1.53

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg)

Figuras y tablas -
Analysis 1.54

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)

Figuras y tablas -
Analysis 1.55

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L)

Figuras y tablas -
Analysis 1.56

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years)

Figuras y tablas -
Analysis 1.57

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education)

Figuras y tablas -
Analysis 1.58

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood

Figuras y tablas -
Analysis 1.59

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood

Figuras y tablas -
Analysis 1.60

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood

Figuras y tablas -
Analysis 1.61

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted)

Figuras y tablas -
Analysis 1.62

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted)

Figuras y tablas -
Analysis 1.63

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC

Figuras y tablas -
Analysis 1.64

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF

Figuras y tablas -
Analysis 1.65

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50

Figuras y tablas -
Analysis 1.66

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25

Figuras y tablas -
Analysis 1.67

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75%

Figuras y tablas -
Analysis 1.68

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75%

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70%

Figuras y tablas -
Analysis 1.69

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70%

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime

Figuras y tablas -
Analysis 1.70

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months

Figuras y tablas -
Analysis 1.71

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma

Figuras y tablas -
Analysis 1.72

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis)

Figuras y tablas -
Analysis 1.73

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax

Figuras y tablas -
Analysis 1.74

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months

Figuras y tablas -
Analysis 1.75

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density

Figuras y tablas -
Analysis 1.76

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density

Figuras y tablas -
Analysis 1.77

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content

Figuras y tablas -
Analysis 1.78

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density

Figuras y tablas -
Analysis 1.79

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density

Figuras y tablas -
Analysis 1.80

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density

Figuras y tablas -
Analysis 1.81

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density

Figuras y tablas -
Analysis 1.82

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density

Figuras y tablas -
Analysis 1.83

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days)

Figuras y tablas -
Analysis 1.84

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days)

Figuras y tablas -
Analysis 1.85

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days)

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days)

Figuras y tablas -
Analysis 1.86

Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days)

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.1

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.2

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.3

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.4

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.5

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.6

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy

Figuras y tablas -
Analysis 2.7

Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.1

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.2

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.3

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.4

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.5

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.6

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.7

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes

Figuras y tablas -
Analysis 3.8

Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS

Figuras y tablas -
Analysis 4.1

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths

Figuras y tablas -
Analysis 4.2

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths

Figuras y tablas -
Analysis 4.3

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths

Figuras y tablas -
Analysis 4.4

Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid

Figuras y tablas -
Analysis 5.1

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid

Figuras y tablas -
Analysis 5.2

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid

Figuras y tablas -
Analysis 5.3

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type

Figuras y tablas -
Analysis 5.4

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid

Figuras y tablas -
Analysis 5.5

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid

Figuras y tablas -
Analysis 5.6

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid

Figuras y tablas -
Analysis 5.7

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid

Figuras y tablas -
Analysis 5.8

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid

Figuras y tablas -
Analysis 5.9

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid

Figuras y tablas -
Analysis 5.10

Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial

Figuras y tablas -
Analysis 6.1

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial

Figuras y tablas -
Analysis 6.2

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial

Figuras y tablas -
Analysis 6.3

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial

Figuras y tablas -
Analysis 6.4

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial

Figuras y tablas -
Analysis 6.5

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial

Figuras y tablas -
Analysis 6.6

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial

Figuras y tablas -
Analysis 6.7

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial

Figuras y tablas -
Analysis 6.8

Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats

Figuras y tablas -
Analysis 7.1

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.2

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.3

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.4

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.5

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.6

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.7

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats

Figuras y tablas -
Analysis 7.8

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome

Figuras y tablas -
Analysis 7.9

Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.1

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.2

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry

Figuras y tablas -
Analysis 8.3

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.4

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.5

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.6

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry

Figuras y tablas -
Analysis 8.7

Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry

Summary of findings 1. Corticosteroids versus placebo or no treatment

Corticosteroids versus placebo or no treatment

Patient or population: pregnant women at high risk of preterm birth receiving a corticosteroid or placebo/no treatment; women with singleton and multiple pregnancy and intact and ruptured membranes
Setting: hospital settings in high‐income countries. For example, data for RDS come from 28 trials in 15 different countries, but only one of these countries is of lower income (Tunisia)
Intervention: corticosteroids (dexamethasone or betamethasone) according to various doses and regimens; some trials with weekly repeats
Comparison: placebo (usually normal saline) or no treatment

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo or no treatment

Risk with corticosteroids

Maternal death

Study population

RR 0.98
(0.06 to 15.50)

3392
(5 RCTs)

⊕⊕⊕⊝
Moderate1

RR based on 2 deaths in a single trial (1 death in each group). Four trials reported zero events

1 per 1000

1 per 1000
(0 to 9)

Chorioamnionitis

Study population

RR 0.83
(0.66 to 1.06)

5546
(15 RCTs)

⊕⊕⊕⊝
Moderate2

48 per 1000

40 per 1000
(32 to 51)

Endometritis (infections)

Study population

RR 1.20
(0.87 to 1.63)

4030
(10 RCTs)

⊕⊕⊕⊝
Moderate2,3

7 of 10 trials reported endometritis; the remaining trials report 'infections'

33 per 1000

39 per 1000
(27 to 59)

Perinatal deaths

Study population

average RR 0.72
(0.58 to 0.89)

6729
(15 RCTs)

⊕⊕⊕
Moderate4

102 per 1000

73 per 1000
(59 to 91)

Respiratory distress syndrome

Study population

average RR 0.66
(0.56 to 0.77)

7764
(28 RCTs)

⊕⊕⊕
Moderate5

176 per 1000

116 per 1000
(98 to 135)

Intraventricular haemorrhage

Study population

average RR 0.55
(0.40 to 0.76)

6093
(16 RCTs)

⊕⊕⊕
Moderate6

51 per 1000

28 per 1000
(20 to 39)

Mean birthweight (grams)

(less is worse)

Absolute risks not calculated

The mean birthweight was 18.47g less (40.83g less to 3.90g more)

6182
(16 RCTs)

⊕⊕⊕
Moderate7

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1Few events and wide confidence interval led to a downgrade for imprecision (‐1). Because maternal death is a rare event and the total population is over 3000 women, we have opted for (‐1) rather than (‐2).
2Wide confidence interval crossing the line of no effect (‐1).
3Value of I2 = 34% with random‐effects model. We have not downgraded evidence for heterogeneity.
4Value of I2 = 37% with random‐effects model. We have not downgraded for heterogeneity. Result downgraded once for risks of bias in included trials (‐1).
5Value of I2 = 47% with random‐effects model. We have not downgraded for heterogeneity. Result downgraded once for risks of bias in included trials (‐1).
6Value of I2 = 33% with random‐effects model. We have not downgraded for heterogeneity. Result downgraded once for risks of bias in included trials (‐1).
7The confidence interval showed a difference at most on average of 40 g in weight; because this is less than 10% of the lightest average for babies in any trial, we have not downgraded evidence for imprecision. We have downgraded the result for risks of bias concerns in included trials (‐1).

Figuras y tablas -
Summary of findings 1. Corticosteroids versus placebo or no treatment
Table 1. Gestational age parameters for included trials

Trial

Year

Minimum

(weeks+days)

Maximum

(weeks+days)

Amorim 1999

1999

28+0

34+6

Attawattanakul 2015

2015

34+0

36+6

Balci 2010

2010

34+0

36+6

Block 1977

1976

Not reported

36+6

Carlan 1991

1991

24+0

34+6

Cararach 1991

1994

28+0

30+6

Collaborative 1981

1981

26+0

37+0

Dexiprom 1999

1999

28+0

34+6

Doran 1980

1980

24+0

34+6

Fekih 2002

2002

26+0

34+6

Gamsu 1989

1989

Not reported

34+6

Garite 1992

1992

24+0

27+6

Goodner 1979

1979

Not reported

33+6

Gyamfi‐Bannerman 2016

2016

34+0

36+6

Kari 1994

1994

24+0

31+6

Khazardoust 2012

(no outcome data)

2012

34+0

37+0

Lewis 1996

1996

24+0

34+6

Liggins 1972b

1972

24+0

36+6

Lopez 1989

1989

27+0

35+0

Mansouri 2010

2010

35+0

36+6

Morales 1989

1989

26+0

34+6

Nelson 1985

1985

28+0

34+6

Parsons 1988

1988

25+0

32+6

Porto 2011

2011

34+0

36+6

Qublan 2001

2001

27+0

34+6

Schutte 1980

1980

26+0

32+6

Shanks 2010

2010

34+0

36+6

Silver 1996

1996

24+0

29+6

Taeusch 1979

1979

Not reported

33+6

Teramo 1980

1980

28+0

35+6

Figuras y tablas -
Table 1. Gestational age parameters for included trials
Comparison 1. Corticosteroids versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Maternal death Show forest plot

5

3392

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.06, 15.50]

1.2 Chorioamnionitis Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

1.3 Endometritis Show forest plot

10

4030

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.87, 1.63]

1.4 Perinatal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

1.5 Neonatal deaths Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

1.6 Fetal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

1.7 Respiratory distress syndrome Show forest plot

28

7764

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.56, 0.77]

1.8 Moderate/severe respiratory distress syndrome Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

1.9 Chronic lung disease Show forest plot

6

818

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.42, 1.79]

1.10 Intraventricular haemorrhage Show forest plot

16

6093

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.40, 0.76]

1.11 Mean birthweight (g) Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

1.12 Death in childhood Show forest plot

4

1010

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.36, 1.27]

1.13 Neurodevelopmental delay in childhood Show forest plot

1

82

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.14, 2.98]

1.14 Death into adulthood Show forest plot

1

988

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.56, 1.81]

1.15 Fever in women after trial entry requiring the use of antibiotics Show forest plot

4

481

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.43, 2.06]

1.16 Intrapartum fever in woman requiring the use of antibiotics Show forest plot

2

319

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.09, 4.89]

1.17 Side effects of therapy in women Show forest plot

6

3572

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.82]

1.18 Admission into adult intensive care unit Show forest plot

2

319

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.26, 2.05]

1.19 Hypertension Show forest plot

1

220

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.36, 2.76]

1.20 Postnatal fever in woman Show forest plot

5

1323

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.64, 1.33]

1.21 Glucose intolerance Show forest plot

1

123

Risk Ratio (M‐H, Fixed, 95% CI)

2.71 [1.14, 6.46]

1.22 Necrotising enterocolitis Show forest plot

10

4702

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.32, 0.78]

1.23 Systemic infection in the first 48 hours of life Show forest plot

8

1753

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.41, 0.88]

1.24 Proven infection while in the neonatal intensive care unit Show forest plot

13

5707

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.55, 1.08]

1.25 Need for mechanical ventilation/CPAP Show forest plot

9

1368

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.56, 0.84]

1.26 Mean duration of mechanical ventilation/CPAP (days) Show forest plot

3

471

Mean Difference (IV, Random, 95% CI)

‐1.91 [‐4.59, 0.76]

1.27 Mean duration of oxygen supplementation (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.28 Surfactant use Show forest plot

5

3556

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.51, 0.90]

1.29 Air leak syndrome Show forest plot

2

2965

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.32, 1.80]

1.30 Apgar < 7 at 5 minutes Show forest plot

10

2419

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.67, 0.98]

1.31 Mean interval between trial entry and birth (days) Show forest plot

3

1513

Mean Difference (IV, Fixed, 95% CI)

0.23 [‐1.86, 2.32]

1.32 Small‐for‐gestational age Show forest plot

5

3478

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.96, 1.28]

1.33 Mean infant HPA axis function (cortisol) Show forest plot

1

27

Mean Difference (IV, Fixed, 95% CI)

3.94 [‐3.12, 11.00]

1.33.1 In babies born < 24 hours after 1st dose

1

6

Mean Difference (IV, Fixed, 95% CI)

9.00 [‐11.93, 29.93]

1.33.2 In babies born 24‐48 hours after 1st dose

1

10

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐8.68, 8.68]

1.33.3 In babies born > 48 hours after 1st dose

1

11

Mean Difference (IV, Fixed, 95% CI)

13.00 [‐1.90, 27.90]

1.34 Admission to neonatal intensive care unit Show forest plot

7

3803

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.84, 0.97]

1.35 Developmental delay in childhood Show forest plot

2

518

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.24, 1.00]

1.36 Cerebral palsy in childhood Show forest plot

5

904

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.34, 1.03]

1.37 Mean childhood weight (kg) Show forest plot

2

333

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.39, 1.00]

1.37.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐0.32, 1.12]

1.37.2 Schutte (females)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐2.40 [‐6.55, 1.75]

1.37.3 Schutte (males)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐3.88, 3.68]

1.38 Mean childhood height (cm) Show forest plot

2

334

Mean Difference (IV, Fixed, 95% CI)

1.02 [‐0.26, 2.29]

1.38.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

1.00 [‐0.39, 2.39]

1.38.2 Schutte (females)

1

39

Mean Difference (IV, Fixed, 95% CI)

1.70 [‐3.08, 6.48]

1.38.3 Schutte (males)

1

45

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐3.79, 4.99]

1.39 Mean childhood head circumference (cm) Show forest plot

2

328

Mean Difference (IV, Fixed, 95% CI)

0.27 [‐0.08, 0.63]

1.39.1 Liggins

1

250

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.11, 0.71]

1.39.2 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐1.05, 0.85]

1.39.3 Schutte (males)

1

42

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐0.51, 1.71]

1.40 Mean childhood VC (% predicted) Show forest plot

2

150

Mean Difference (IV, Fixed, 95% CI)

‐1.68 [‐5.12, 1.75]

1.40.1 Liggins

1

75

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐5.12, 6.52]

1.40.2 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐2.60 [‐8.65, 3.45]

1.40.3 Schutte (males)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐3.30 [‐9.27, 2.67]

1.41 Mean childhood FEV1 (% predicted) Show forest plot

1

75

Mean Difference (IV, Fixed, 95% CI)

‐4.73 [‐10.13, 0.67]

1.41.1 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐2.50 [‐11.24, 6.24]

1.41.2 Schutte (males)

1

39

Mean Difference (IV, Fixed, 95% CI)

‐6.10 [‐12.96, 0.76]

1.42 Mean childhood FEV1/VC Show forest plot

2

150

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐3.63, 1.76]

1.42.1 Liggins

1

75

Mean Difference (IV, Random, 95% CI)

1.00 [‐2.57, 4.57]

1.42.2 Schutte (females)

1

36

Mean Difference (IV, Random, 95% CI)

0.00 [‐5.56, 5.56]

1.42.3 Schutte (males)

1

39

Mean Difference (IV, Random, 95% CI)

‐3.00 [‐6.14, 0.14]

1.43 Mean childhood systolic blood pressure (mmHg) Show forest plot

1

223

Mean Difference (IV, Fixed, 95% CI)

‐1.60 [‐4.06, 0.86]

1.44 Visual impairment in childhood Show forest plot

2

166

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.24, 1.23]

1.45 Hearing impairment in childhood Show forest plot

2

166

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.04, 9.87]

1.46 Intellectual impairment in childhood Show forest plot

3

778

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.44, 1.69]

1.47 Behavioural/learning difficulties in childhood Show forest plot

1

90

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.35, 2.09]

1.48 Mean adult insulin (log values) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.48.1 Fasting

1

435

Mean Difference (IV, Fixed, 95% CI)

0.08 [‐0.03, 0.19]

1.48.2 30 minutes following a 75 g oral glucose tolerance test

1

412

Mean Difference (IV, Fixed, 95% CI)

0.16 [0.04, 0.28]

1.48.3 120 minutes following a 75 g oral glucose tolerance test

1

428

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.27, 0.07]

1.49 Mean adult glucose (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.49.1 Fasting

1

432

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.09, 0.11]

1.49.2 30 minutes following a 75 g oral glucose tolerance test

1

413

Mean Difference (IV, Fixed, 95% CI)

0.19 [‐0.14, 0.52]

1.49.3 120 minutes following a 75 g oral glucose tolerance test

1

410

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.52, ‐0.02]

1.50 Mean adult weight (kg) Show forest plot

2

538

Mean Difference (IV, Random, 95% CI)

‐0.83 [‐6.41, 4.76]

1.50.1 Schutte (females)

1

37

Mean Difference (IV, Random, 95% CI)

‐6.00 [‐12.93, 0.93]

1.50.2 Schutte (males)

1

43

Mean Difference (IV, Random, 95% CI)

‐1.00 [‐9.91, 7.91]

1.50.3 Liggins

1

458

Mean Difference (IV, Random, 95% CI)

2.57 [‐0.72, 5.86]

1.51 Mean adult height (cm) Show forest plot

2

537

Mean Difference (IV, Fixed, 95% CI)

0.91 [‐0.28, 2.10]

1.51.1 Schutte (females)

1

36

Mean Difference (IV, Fixed, 95% CI)

‐1.00 [‐5.37, 3.37]

1.51.2 Schutte (males)

1

43

Mean Difference (IV, Fixed, 95% CI)

3.00 [‐2.30, 8.30]

1.51.3 Liggins (females)

1

234

Mean Difference (IV, Fixed, 95% CI)

1.17 [‐0.65, 2.99]

1.51.4 Liggins (males)

1

224

Mean Difference (IV, Fixed, 95% CI)

0.75 [‐1.03, 2.53]

1.52 Mean adult head circumference (cm) Show forest plot

2

537

Mean Difference (IV, Fixed, 95% CI)

0.03 [‐0.33, 0.38]

1.52.1 Schutte (females)

1

37

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐1.03, 1.03]

1.52.2 Schutte (males)

1

42

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.37, 0.97]

1.52.3 Liggins

1

458

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.34, 0.46]

1.53 Mean adult skinfold thickness (log values) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.53.1 Triceps

1

456

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.11, 0.07]

1.53.2 Biceps

1

456

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.11, 0.09]

1.53.3 Subscapular

1

441

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.08, 0.10]

1.53.4 Suprailiac

1

452

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.12, 0.10]

1.54 Mean adult systolic blood pressure (mmHg) Show forest plot

2

545

Mean Difference (IV, Random, 95% CI)

‐1.53 [‐4.50, 1.44]

1.54.1 Schutte (females)

1

38

Mean Difference (IV, Random, 95% CI)

‐4.00 [‐9.12, 1.12]

1.54.2 Schutte (males)

1

52

Mean Difference (IV, Random, 95% CI)

‐3.00 [‐7.17, 1.17]

1.54.3 Liggins

1

455

Mean Difference (IV, Random, 95% CI)

0.55 [‐1.88, 2.98]

1.55 Mean adult HPA axis function (mean log fasting cortisol) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.56 Mean cholesterol in adulthood (mmol/L) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.57 Mean age at puberty (years) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.57.1 Schutte (females)

1

38

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.94, 0.94]

1.58 Educational achievement by adulthood (university or polytechnic education) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.59 Visual impairment in adulthood Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.60 Hearing impairment in adulthood Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.61 Intellectual impairment in adulthood Show forest plot

2

273

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.01, 4.95]

1.62 Mean adult FVC (% predicted) Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐3.16, 1.76]

1.63 Mean adult FEV1 (% predicted) Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐2.31, 3.11]

1.64 Mean adult FEV1/FVC Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.01, 0.03]

1.65 Mean adult PEF Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

2.20 [‐0.77, 5.17]

1.66 Mean adult F50 Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

3.00 [‐1.57, 7.57]

1.67 Mean adult F25 Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐3.82, 4.62]

1.68 Mean adult FEF 25%‐75% Show forest plot

1

383

Mean Difference (IV, Fixed, 95% CI)

2.20 [‐2.10, 6.50]

1.69 FEV1/FVC < 70% Show forest plot

1

383

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.49, 1.57]

1.70 Asthma diagnosed by Doctor in lifetime Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

1.71 Wheezing in last 12 months Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.84, 1.35]

1.72 Current Asthma Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.74, 1.48]

1.73 Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis) Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.69, 2.59]

1.74 Spontaneous pneumothorax Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.07, 17.66]

1.75 Shortness of breath at anytime in the last 12 months Show forest plot

1

534

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.80, 1.31]

1.76 Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.04, 0.04]

1.77 Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.01, 0.01]

1.78 Mean adult total body BMC (grams) bone mineral content Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

18.00 [‐151.30, 187.30]

1.79 Mean adult total body aBMD (g/cm3) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐0.03, 0.03]

1.80 Mean adult femoral neck aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.03, 0.07]

1.81 Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.02, 0.06]

1.82 Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.04, 0.06]

1.83 Mean total proximal femur aBMD (g/cm2) areal bone mineral density Show forest plot

1

174

Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.03, 0.07]

1.84 Mean length of antenatal hospitalisation (days) Show forest plot

1

218

Mean Difference (IV, Fixed, 95% CI)

0.50 [‐1.40, 2.40]

1.85 Mean length of postnatal hospitalisation (days) Show forest plot

1

218

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐1.72, 1.72]

1.86 Mean length of neonatal hospitalisation (days) Show forest plot

5

788

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.51, 0.87]

Figuras y tablas -
Comparison 1. Corticosteroids versus placebo or no treatment
Comparison 2. Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Chorioamnionitis ‐ single or multiple pregnancy Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

2.1.1 In women delivering singleton pregnancies

7

4682

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.56, 1.01]

2.1.2 In women delivering multiple pregnancies

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.04, 4.49]

2.1.3 Mixed population

8

790

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.70, 1.57]

2.2 Perinatal death ‐ single or multiple pregnancy Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.59, 0.89]

2.2.1 In babies born from singleton pregnancies

6

5182

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.54, 1.05]

2.2.2 In babies born from multiple pregnancies

2

252

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.37, 1.47]

2.2.3 Mixed population

9

1295

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.49, 0.94]

2.3 Neonatal death ‐ single or multiple pregnancy Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

2.3.1 In babies born from singleton pregnancies

9

5335

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.61, 0.92]

2.3.2 In babies born from multiple pregnancies

2

236

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.39, 1.61]

2.3.3 Mixed population

13

1617

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.46, 0.78]

2.4 Fetal death ‐ single or multiple pregnancy Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.73, 1.29]

2.4.1 In babies born from singleton pregnancies

6

5182

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.75, 1.45]

2.4.2 In babies born from multiple pregnancies

2

252

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.20, 1.40]

2.4.3 Mixed population

9

1295

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.50, 1.99]

2.5 Respiratory distress syndrome ‐ single or multiple pregnancy Show forest plot

28

7762

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.59, 0.78]

2.5.1 In babies born from singleton pregnancies

15

6081

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.50, 0.77]

2.5.2 In babies born from multiple pregnancies

4

320

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.67, 1.22]

2.5.3 Mixed population

13

1361

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.53, 0.89]

2.6 IVH ‐ single or multiple pregnancy Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

2.6.1 In babies born from singleton pregnancies

8

4782

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.36, 0.75]

2.6.2 In babies born from multiple pregnancies

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.07, 2.06]

2.6.3 Mixed population

8

1174

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.44, 0.81]

2.7 Birthweight ‐ single or multiple pregnancy Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐17.61 [‐39.95, 4.74]

2.7.1 In babies born from singleton pregnancy

9

4948

Mean Difference (IV, Fixed, 95% CI)

‐24.12 [‐48.27, 0.03]

2.7.2 In babies born from multiple pregnancies

1

150

Mean Difference (IV, Fixed, 95% CI)

82.36 [‐146.23, 310.95]

2.7.3 Mixed population

7

1084

Mean Difference (IV, Fixed, 95% CI)

16.77 [‐44.16, 77.69]

Figuras y tablas -
Comparison 2. Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy
Comparison 3. Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Chorioamnionitis ‐ intact or ruptured membranes Show forest plot

15

5517

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.67, 1.07]

3.1.1 In women with intact membranes at 1st dose

5

1437

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.50, 1.40]

3.1.2 In women with ruptured membranes at 1st dose

7

959

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.69, 1.40]

3.1.3 Not reported or mixed population

4

3121

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.47, 1.06]

3.2 Endometritis ‐ intact or ruptured membranes Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.80, 1.80]

3.2.1 In women with intact membranes at 1st dose

2

289

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.37, 4.01]

3.2.2 In women with ruptured membranes at 1st dose

4

477

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.35, 2.97]

3.2.3 Not reported or mixed population

5

3264

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.81, 2.13]

3.3 Perinatal death ‐ intact or ruptured membranes Show forest plot

15

6700

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.60, 0.90]

3.3.1 In babies born from pregnancies with intact membranes at 1st dose

4

1332

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.70, 1.08]

3.3.2 In babies born from pregnancies with ruptured membranes at 1st dose

4

733

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.39, 0.90]

3.3.3 Not reported or mixed population

8

4635

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.49, 1.03]

3.4 Neonatal deaths ‐ intact or ruptured membranes Show forest plot

22

7163

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

3.4.1 In babies born from pregnancies with intact membranes at 1st dose

4

1236

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.58, 1.03]

3.4.2 In babies born from pregnancies with ruptured membranes at 1st dose

8

1024

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.46, 0.83]

3.4.3 Not reported or mixed population

11

4903

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.53, 0.88]

3.5 Fetal death ‐ intact or ruptured membranes Show forest plot

15

6634

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.26]

3.5.1 In babies born from pregnancies with intact membranes at 1st dose

4

1332

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.73, 1.64]

3.5.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

790

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.46, 1.61]

3.5.3 Not reported or mixed population

7

4512

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.44, 1.35]

3.6 RDS ‐ intact or ruptured membranes Show forest plot

28

7738

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.56, 0.76]

3.6.1 In babies born from pregnancies with intact membranes at 1st dose

6

1721

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.50, 0.80]

3.6.2 In babies born from pregnancies with ruptured membranes at 1st dose

12

1129

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.55, 0.90]

3.6.3 Not reported or mixed population

14

4888

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.46, 0.81]

3.7 IVH ‐ intact or ruptured membranes Show forest plot

15

5868

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

3.7.1 In babies born from pregnancies with intact membranes at 1st dose

5

1394

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.35, 0.72]

3.7.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

895

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.28, 0.79]

3.7.3 Not reported or mixed population

6

3579

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.49, 1.07]

3.8 Birthweight ‐ intact or ruptured membranes Show forest plot

16

6153

Mean Difference (IV, Fixed, 95% CI)

‐19.52 [‐41.81, 2.78]

3.8.1 In babies born from pregnancies with intact membranes at 1st dose

4

1301

Mean Difference (IV, Fixed, 95% CI)

‐30.27 [‐100.43, 39.89]

3.8.2 In babies born from pregnancies with ruptured membranes at 1st dose

5

835

Mean Difference (IV, Fixed, 95% CI)

‐49.72 [‐113.91, 14.46]

3.8.3 Not reported or mixed population

8

4017

Mean Difference (IV, Fixed, 95% CI)

‐13.44 [‐38.71, 11.83]

Figuras y tablas -
Comparison 3. Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose
Comparison 4. Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 RDS Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

4.1.1 Hypertension syndrome

5

382

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.35, 0.72]

4.1.2 No hypertension syndrome or hypertension syndromes excluded

9

2660

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.47, 0.71]

4.1.3 Hypertension not reported separately

18

4722

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.66, 0.85]

4.2 Perinatal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.60, 0.92]

4.2.1 Hypertension syndrome

2

313

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.42, 2.10]

4.2.2 No hypertension syndrome or hypertension syndromes excluded

3

1394

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.39, 1.29]

4.2.3 Hypertension not reported separately

11

5022

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.52, 0.93]

4.3 Fetal deaths Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

4.3.1 Women with hypertension syndrome

3

331

Risk Ratio (M‐H, Fixed, 95% CI)

1.73 [0.91, 3.28]

4.3.2 No hypertension syndrome or hypertension syndromes excluded

4

1644

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.49, 1.08]

4.3.3 Hypertension not reported separately

10

4754

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.67, 1.98]

4.4 Neonatal deaths Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

4.4.1 Hypertension syndrome

2

278

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.87]

4.4.2 No hypertension syndrome or hypertension syndromes excluded

3

1306

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.61, 1.09]

4.4.3 Hypertension not reported separately

18

5604

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.54, 0.82]

Figuras y tablas -
Comparison 4. Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials
Comparison 5. Corticosteroids versus placebo or no treatment ‐ type of steroid

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Chorioamnionitis ‐ type of steroid Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

5.1.1 In women treated with dexamethasone

5

769

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.89, 2.05]

5.1.2 In women treated with betamethasone

10

4777

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.50, 0.90]

5.2 Endometritis ‐ type of steroid Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.81, 1.80]

5.2.1 In women treated with dexamethasone

4

536

Risk Ratio (M‐H, Random, 95% CI)

1.71 [0.86, 3.43]

5.2.2 In women treated with betamethasone

6

3494

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.63, 1.45]

5.3 Perinatal death ‐ type of steroid Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

5.3.1 In babies treated with dexamethasone

5

1420

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.46, 1.11]

5.3.2 In babies treated with betamethasone

10

5309

Risk Ratio (M‐H, Random, 95% CI)

0.73 [0.56, 0.94]

5.4 Neonatal deaths by steroid type Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

5.4.1 In babies treated with dexamethasone

6

1468

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.55, 0.94]

5.4.2 In babies treated with betamethasone

16

5720

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.55, 0.83]

5.5 Fetal death ‐ type of steroid Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

5.5.1 In babies treated with dexamethasone

5

1420

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.48, 1.60]

5.5.2 In babies treated with betamethasone

10

5309

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.73, 1.39]

5.6 Respiratory distress syndrome ‐ type of steroid Show forest plot

28

7764

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.56, 0.77]

5.6.1 In babies treated with dexamethasone

7

1651

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.61, 0.98]

5.6.2 In babies treated with betamethasone

20

6095

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.50, 0.73]

5.6.3 Steroid type not reported

1

18

Risk Ratio (M‐H, Random, 95% CI)

1.62 [0.08, 34.66]

5.7 IVH ‐ type of steroid Show forest plot

16

6093

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.40, 0.76]

5.7.1 In babies treated with dexamethasone

6

897

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.18, 1.26]

5.7.2 In babies treated with betamethasone

10

5196

Risk Ratio (M‐H, Random, 95% CI)

0.53 [0.40, 0.72]

5.8 Birthweight ‐ type of steroid Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

5.8.1 In babies treated with dexamethasone

4

686

Mean Difference (IV, Fixed, 95% CI)

‐17.04 [‐75.48, 41.41]

5.8.2 In babies treated with betamethasone

12

5496

Mean Difference (IV, Fixed, 95% CI)

‐18.71 [‐42.92, 5.50]

5.9 Moderate/severe respiratory distress syndrome ‐ type of steroid Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

5.9.1 Dexamethasone

2

219

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.46, 1.44]

5.9.2 Betamethasone

4

1467

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.27, 0.90]

5.10 Chronic lung disease ‐ type of steroid Show forest plot

6

818

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.42, 1.79]

5.10.1 Dexamethasone

2

219

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.72, 1.90]

5.10.2 Betamethasone

4

599

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.26, 2.28]

Figuras y tablas -
Comparison 5. Corticosteroids versus placebo or no treatment ‐ type of steroid
Comparison 6. Corticosteroids versus placebo or no treatment ‐ decade of trial

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Chorioamnionitis ‐ decade of trial Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

6.1.1 In women from trials conducted in 1970s

2

1237

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.46, 1.17]

6.1.2 In women from trials conducted in 1980s

3

276

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.25, 1.01]

6.1.3 In women from trials conducted in 1990s

6

755

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.80, 1.74]

6.1.4 in women from trials conducted in the 2000's

2

257

Risk Ratio (M‐H, Fixed, 95% CI)

2.02 [0.59, 6.95]

6.1.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.35, 1.07]

6.2 Endometritis ‐ decade of trial Show forest plot

10

4030

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.87, 1.63]

6.2.1 In women from trials conducted in 1970s

2

219

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [0.81, 4.27]

6.2.2 In women from trials conducted in 1980s

1

71

Risk Ratio (M‐H, Fixed, 95% CI)

2.30 [0.88, 6.06]

6.2.3 In women from trials conducted in 1990s

4

574

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.53, 1.44]

6.2.4 In women from trials conducted in the 2000's

3

3166

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.69, 2.01]

6.3 Perinatal deaths ‐ decade of trial Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

6.3.1 In babies from trials conducted in 1970s

6

1994

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.50, 1.00]

6.3.2 In babies from trials conducted in 1980s

3

879

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.42]

6.3.3 In babies from trials conducted in 1990s

3

615

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.43, 0.93]

6.3.4 in babies from trials conducted in 2000's

2

414

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.31, 0.70]

6.3.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Random, 95% CI)

4.91 [0.24, 102.09]

6.4 Neonatal deaths decade of trial Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

6.4.1 In babies from trials conducted in 1970s

7

1968

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.56, 0.92]

6.4.2 In babies from trials conducted in 1980s

6

1096

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.70, 1.37]

6.4.3 In babies from trials conducted in 1990s

5

758

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.36, 0.84]

6.4.4 In babies from trials conducted in 2000s

3

539

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.31, 0.64]

6.4.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

6.5 Fetal death ‐ decade of trial Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

6.5.1 In babies from trials conducted in 1970s

6

1994

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.67, 1.34]

6.5.2 In babies from trials conducted in 1980s

3

879

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.52, 2.00]

6.5.3 In babies from trials conducted in 1990s

3

615

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.49, 2.36]

6.5.4 In babies from trials conducted in 2000's

2

414

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.19, 4.50]

6.5.5 In trials conducted in 2010s

1

2827

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

6.6 RDS ‐ decade of trial Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

6.6.1 In babies from trials conducted in 1970s

7

1939

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.43, 0.69]

6.6.2 In babies from trials conducted in 1980s

7

1167

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.59, 0.88]

6.6.3 In babies from trials conducted in 1990s

7

798

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.65, 0.91]

6.6.4 In babies from trials conducted in 2000s

5

839

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.26, 0.59]

6.6.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.61, 1.04]

6.7 IVH ‐ decade of trial Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

6.7.1 In babies from trials conducted in 1970s

4

1646

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.29, 0.85]

6.7.2 In babies from trials conducted in 1980s

2

238

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.39, 0.94]

6.7.3 In babies from trials conducted in 1990s

5

722

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.42, 0.87]

6.7.4 In babies from trials conducted in 2000s

3

466

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.15, 0.73]

6.7.5 In trials from 2010s

2

3021

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

6.8 Birthweight ‐ decade of trial Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

6.8.1 In babies from trials conducted in 1970s

4

1739

Mean Difference (IV, Fixed, 95% CI)

‐9.54 [‐83.55, 64.47]

6.8.2 In babies from trials conducted in 1980s

3

280

Mean Difference (IV, Fixed, 95% CI)

‐19.60 [‐108.55, 69.35]

6.8.3 In babies from trials conducted in 1990s

4

569

Mean Difference (IV, Fixed, 95% CI)

‐33.13 [‐102.39, 36.13]

6.8.4 In babies from trials conducted in 2000s

3

573

Mean Difference (IV, Fixed, 95% CI)

‐20.77 [‐61.95, 20.41]

6.8.5 In trials in 2010s

2

3021

Mean Difference (IV, Fixed, 95% CI)

‐15.18 [‐48.66, 18.29]

Figuras y tablas -
Comparison 6. Corticosteroids versus placebo or no treatment ‐ decade of trial
Comparison 7. Corticosteroids versus placebo or no treatment ‐ weekly repeats

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Chorioamnionitis ‐ Protocol with weekly repeats Show forest plot

15

5546

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.66, 1.06]

7.1.1 In women treated with single courses only

7

4659

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.61, 1.11]

7.1.2 In women treated with courses including weekly repeats

8

887

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.57, 1.25]

7.2 Endometritis ‐ protocol with weekly repeats Show forest plot

10

4030

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.81, 1.80]

7.2.1 In women treated with single courses only

5

3450

Risk Ratio (M‐H, Random, 95% CI)

1.04 [0.66, 1.64]

7.2.2 In women treated with courses including weekly repeats

5

580

Risk Ratio (M‐H, Random, 95% CI)

1.46 [0.72, 2.95]

7.3 Perinatal death ‐ protocol with weekly repeats Show forest plot

15

6729

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

7.3.1 In babies treated with single course only

11

6250

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.61, 0.99]

7.3.2 In babies treated with courses including weekly repeats

4

479

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.44, 0.97]

7.4 Neonatal death ‐ protocol with weekly repeats Show forest plot

22

7188

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.59, 0.81]

7.4.1 In babies treated with single course only

14

6266

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.63, 0.95]

7.4.2 In babies treated with courses including weekly repeats

8

922

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.43, 0.72]

7.5 Fetal death ‐ protocol with weekly repeats Show forest plot

15

6729

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.30]

7.5.1 In babies treated with single course only

11

6250

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.68, 1.25]

7.5.2 In babies treated with courses including weekly repeats

4

479

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.64, 2.87]

7.6 RDS ‐ protocol with weekly repeats Show forest plot

28

7764

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.60, 0.74]

7.6.1 In babies treated with single course only

19

6818

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.61, 0.79]

7.6.2 In babies treated with courses including weekly repeats

9

946

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.52, 0.72]

7.7 IVH‐ protocol with weekly repeats Show forest plot

16

6093

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.44, 0.70]

7.7.1 In babies treated with single course only

9

5216

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.33, 0.76]

7.7.2 In babies treated with courses including weekly repeats

7

877

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.45, 0.78]

7.8 Birthweight ‐ protocol with weekly repeats Show forest plot

16

6182

Mean Difference (IV, Fixed, 95% CI)

‐18.47 [‐40.83, 3.90]

7.8.1 In babies treated with single course only

12

5773

Mean Difference (IV, Fixed, 95% CI)

‐18.24 [‐42.12, 5.65]

7.8.2 In babies treated with courses including weekly repeats

4

409

Mean Difference (IV, Fixed, 95% CI)

‐20.10 [‐83.79, 43.60]

7.9 Moderate/severe respiratory distress syndrome Show forest plot

6

1686

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.38, 0.91]

7.9.1 Single course

3

1259

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.44, 0.83]

7.9.2 Weekly repeats

3

427

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.13, 1.32]

Figuras y tablas -
Comparison 7. Corticosteroids versus placebo or no treatment ‐ weekly repeats
Comparison 8. Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Chorioamnionitis ‐ gestational age at trial entry Show forest plot

15

5506

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.65, 1.05]

8.1.1 Less than or equal to 35 weeks + 0 days

13

2304

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.70, 1.19]

8.1.2 Greater than or equal to 34 weeks + 0 days

3

3202

Risk Ratio (M‐H, Fixed, 95% CI)

0.57 [0.33, 0.99]

8.2 Perinatal death ‐ gestational age at trial entry Show forest plot

15

6687

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.59, 0.88]

8.2.1 Less than or equal to 35 weeks + 0 days

13

3391

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.58, 0.87]

8.2.2 Greater than or equal to 34 weeks + 0 days

3

3296

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.29, 3.67]

8.3 Neonatal death ‐ gestational age at trial engry Show forest plot

22

7146

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.57, 0.79]

8.3.1 Less than or equal to 35 weeks + 0 days

20

3855

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.57, 0.79]

8.3.2 Greater than or equal to 34 weeks + 0 days

3

3291

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.22, 3.07]

8.4 Fetal death ‐ gestational age at trial entry Show forest plot

15

6687

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.72, 1.27]

8.4.1 Less than or equal to 35 weeks + 0 days

13

3391

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.71, 1.25]

8.4.2 Greater than or equal to 34 weeks + 0 days

3

3296

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.28, 9.37]

8.5 RDS‐ gestational age at trial entry Show forest plot

28

7722

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.60, 0.73]

8.5.1 Less than or equal to 35 weeks + 0 days

23

3939

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.58, 0.73]

8.5.2 Greater than or equal to 34 weeks + 0 days

6

3783

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.56, 0.91]

8.6 IVH ‐ gestational age at trial entry Show forest plot

16

6051

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.44, 0.70]

8.6.1 Less than or equal to 35 weeks + 0 days

13

2639

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.42, 0.68]

8.6.2 Greater than or equal to 34 weeks + 0 days

4

3412

Risk Ratio (M‐H, Fixed, 95% CI)

4.91 [0.24, 102.09]

8.7 Birthweight ‐ gestational age at trial entry Show forest plot

16

6140

Mean Difference (IV, Fixed, 95% CI)

‐17.45 [‐39.76, 4.86]

8.7.1 Less than or equal to 35 weeks + 0 days

11

2352

Mean Difference (IV, Fixed, 95% CI)

‐17.89 [‐63.14, 27.36]

8.7.2 Greater than or equal to 34 weeks + 0 days

6

3788

Mean Difference (IV, Fixed, 95% CI)

‐17.31 [‐42.96, 8.34]

Figuras y tablas -
Comparison 8. Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry