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بررسی تاثیر استفاده زودهنگام (< 8 روزه) از کورتیکواستروئیدهای سیستمیک پس از زایمان برای پیشگیری از دیسپلازی برونکوپولمونری در نوزادان پره‌ترم

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Referencias

Anttila 2005 {published data only}

Anttila E, Peltonemi O, Haumont D, Herting E, ter Horst H, Heinonen K, et al. Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta‐analysis evaluating the duration of dexamethasone therapy. European Journal of Pediatrics 2005;164(8):472‐81. [DOI: 10.1007/s00431‐005‐1645‐8; PUBMED: 15864643]CENTRAL

Baden 1972 {published data only}

Baden M, Bauer CR, Cole E, Klein G, Taeusch HW, Stern L. A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics 1972;50(4):526‐34. [PUBMED: 4561296]CENTRAL
Fitzhardinge PM, Eisen A, Lejtenyi C, Metrakos K, Ramsay M. Sequelae of early steroid administration to the newborn infant. Pediatrics 1974;53(6):877‐83. [PUBMED: 4598934]CENTRAL

Batton 2012 {published data only}

Batton BJ, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Feasibility study of early blood pressure management in extremely preterm infants. Journal of Pediatrics 2012;161(1):65‐9. [DOI: 10.1016/j.jpeds.2012.01.014; PUBMED: 22336574]CENTRAL

Baud 2016 {published data only}

Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. PREMILOC Trial Study Group. Effect of early low‐dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double‐blind, placebo‐controlled, multicentre, randomised trial. Lancet 2016;387(10030):1827‐36. [DOI: 10.1016/S0140‐6736(16)00202‐6; PUBMED: 26916176]CENTRAL
Baud O, Trousson C, Biran V, Leroy E, Mohamed D, Alberti C, PREMILOC Trial Group. Association between early low‐dose hydrocortisone therapy in extremely preterm neonates and neurodevelopmental outcomes at 2 years of age. JAMA 2017;317(13):1329‐37. [DOI: 10.1001/jama.2017.2692; PUBMED: 28384828]CENTRAL

Biswas 2003 {published data only}

Biswas S. Personal communication. email2002. CENTRAL
Biswas S, Buffery J, Enoch H, Bland M, Markiewicz M, Walters D. Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial ‐ thyroid hormone replacement in neonates. Pediatric Research 2003;53(1):48‐56. [DOI: 10.1203/00006450‐200301000‐00011; PUBMED: 12508081]CENTRAL

Bonsante 2007 {published data only}

Bonsante F, Latorre G, Lacobelli S, Forziati V, Laforgia N, Esposito L, et al. Early low‐dose hydrocortisone in very preterm infants: a randomized placebo‐controlled trial. Neonatology 2007;91(4):217‐21. [DOI: 10.1159/000098168; PUBMED: 17568152]CENTRAL

Efird 2005 {published data only}

Efird MM, Heerens AT, Gordon PV, Bose CL, Young DA. A randomized‐controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants. Journal of Perinatology 2005;25(2):119‐24. [DOI: 10.1038/sj.jp.7211193; PUBMED: 15329742]CENTRAL

Garland 1999 {published data only}

Garland JS, Alex CP, Pauly TH, Whitehead VL, Brand J, Winston JF, et al. A three‐day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial. Pediatrics 1999;104(1 Pt 1):91‐9. [PUBMED: 10390266]CENTRAL

Halac 1990 {published data only}

Halac E, Halac J, Begue EF, Casañas JM, Indiveri DR, Petit JF, et al. Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. Journal of Pediatrics 1990;117(1 Pt 1):132‐8. [PUBMED: 2196355]CENTRAL

Hochwald 2014 {published data only}

Hochwald O, Palegra G, Osiovich O. Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants. Indian Journal of Pediatrics 2014;81(8):808‐10. [DOI: 10.1007/s12098‐013‐1151‐3; PUBMED: 23904065]CENTRAL

Kopelman 1999 {published data only}

Kopelman AE, Moise AA, Holbert D, Hegemier SE. A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants. Journal of Pediatrics 1999;135(3):345‐50. [PUBMED: 10484801]CENTRAL

Lauterbach 2006 {published data only}

Lauterbach R, Szymura‐Oleksiak J, Pawlik D, Warchol J, Lisowska‐Miszczyk I, Rytlewski K. Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: a pilot clinical study. Journal of Maternal‐Fetal & Neonatal Medicine 2006;19(7):433‐8. [DOI: 10.1080/14767050600736754; PUBMED: 16923699]CENTRAL

Lin 1999 {published data only}

Lin YJ, Yeh TF, Hsieh WS, Chi YC, Lin HC, Lin CH. Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy. Pediatric Pulmonology 1999;27(1):21‐6. [PUBMED: 10023787]CENTRAL

Mukhopadhyay 1998 {published data only}

Mukhopadhyay K, Kumar P, Narang A. Role of early postnatal dexamethasone in respiratory distress syndrome. Indian Pediatrics 1998;35(2):117‐22. [PUBMED: 9707853]CENTRAL

Ng 2006 {published data only}

Ng PC, Lee CH, Bnur FL, Chan IH, Lee AW, Wong E, et al. A double‐blind randomized controlled study of a stress dose of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics 2006;117(2):367‐75. [DOI: 10.1542/peds.2005‐0869; PUBMED: 16452355]CENTRAL

Peltoniemi 2005 {published data only}

Peltoniemi O, Kari A, Heinonen K, Saarela T, Nikolajev K, Andersson S, et al. Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high‐risk infants. Journal of Pediatrics 2005;146(5):632‐7. [DOI: 10.1016/j.jpeds.2004.12.040; PUBMED: 15870666]CENTRAL
Peltoniemi OM, Lano A, Puosi R, Yliherva A, Bonsante F, Kari MA, et al. Neonatal Hydrocortisone Working Group. Trial of early neonatal hydrocortisone: two‐year follow‐up. Neonatology 2009;95(3):240‐7. [DOI: 10.1159/000164150; PUBMED: 18931525]CENTRAL
Peltoniemi OM, Lano A, Yliherva A, Kari MA, Hallman M, Neonatal Hydrocortisone Working Group. Randomised trial of early neonatal hydrocortisone demonstrates potential undesired effects on neurodevelopment at preschool age. Acta Paediatrica 2016;105(2):159‐64. [DOI: 10.1111/apa.13074; PUBMED: 26058477]CENTRAL

Rastogi 1996 {published data only}

Morales P, Rastogi A, Bez ML, Akintorin SM, Pyati S, Andes SM, et al. Effect of dexamethasone therapy on the neonatal ductus arteriosus. Pediatric Cardiology 1998;19(3):225‐9. [DOI: 10.1007/s002469900290; PUBMED: 9568218]CENTRAL
Rastogi A, Akintorin SM, Bez ML, Morales P, Pildes PS. A controlled trial of dexamethasone to prevent bronchopulmonary dysplasia in surfactant‐treated infants. Pediatrics 1996;98(2 Pt 1):204‐10. [PUBMED: 8692619]CENTRAL

Romagnoli 1999 {published data only}

Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G. Controlled trial of early dexamethasone treatment for the prevention of chronic lung disease in preterm infants: a 3‐year follow‐up. Pediatrics 2002;109(6):e85. [PUBMED: 12042579]CENTRAL
Romagnoli C, Zecca E, Vento G, De Carolis MP, Papacci P, Tortorolo G. Early postnatal dexamethasone for the prevention of chronic lung disease in high‐risk preterm infants. Intensive Care Medicine 1999;25(7):717‐21. [PUBMED: 10470576]CENTRAL
Romagnoli C, Zecca E, Vento G, Maggio L, Papacci P, Tortorolo G. Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized controlled trial. Pharmacology 1999;59(5):266‐74. [DOI: 28329; PUBMED: 10529659]CENTRAL

Sanders 1994 {published data only}

Sanders RJ, Cox C, Phelps DL, Sinkin RA. Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome. Pediatric Research 1994;36(1 Pt 1):122‐8. [DOI: 10.1203/00006450‐199407001‐00022; PUBMED: 7936832]CENTRAL
Sinkin RA. Personal communication. email2002. CENTRAL

Shinwell 1996 {published data only}

Shinwell ES. Early dexamethasone therapy is associated with increased incidence of cerebral palsy. Hot Topics' 99 in Neonatology1999:240‐54. CENTRAL
Shinwell ES. Personal communication. email2002. CENTRAL
Shinwell ES, Karplus M, Reich D, Weintraub Z, Blazer S, Bader D, et al. Early postnatal dexamethasone treatment and incidence of cerebral palsy. Archives of Disease in Childhood. Fetal and Neonatal Edition 2000;83(3):F177‐81. [PUBMED: 11040164]CENTRAL
Shinwell ES, Karplus M, Zmora E, Reich D, Rothschild A, Blazer S, et al. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Archives of Disease in Childhood. Fetal and Neonatal Edition 1996;74(1):F33‐7. [PUBMED: 8653433]CENTRAL

Sinkin 2000 {published data only}

D'Angio CT, Maniscalco WM, Ryan RM, Avissar NE, Basavegowda K, Sinkin RA. Vascular endothelial growth factor in pulmonary lavage fluid from premature infants: effects of age and postnatal dexamethasone. Biology of the Neonate 1999;76(5):266‐73. [DOI: 14168; PUBMED: 10516393]CENTRAL
Sinkin RA. Personal communication. email2002. CENTRAL
Sinkin RA, Dweck HS, Horgan MJ, Gallaher KJ, Cox C, Maniscalco WM, et al. Early dexamethasone ‐ attempting to prevent chronic lung disease. Pediatrics 2000;105(3 Pt 1):542‐8. [PUBMED: 10699107]CENTRAL

Soll 1999 {published data only}

Soll RF, Vermont Oxford Network Steroid Study Group. Early postnatal dexamethasone therapy for the prevention of chronic lung disease. Pediatric Research 1999;45:226A. CENTRAL
Vermont Oxford Network Steroid Study Group. Early postnatal dexamethasone therapy for the prevention of chronic lung disease. Pediatrics 2001;108(3):741‐8. [PUBMED: 11533345]CENTRAL

Stark 2001 {published data only}

Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S, et al. National Institute of Child Health and Human Development Neonatal Research Network. Adverse effects of early dexamethasone in extremely‐low‐birth‐weight infants. New England Journal of Medicine 2001;344(2):95‐101. [DOI: 10.1056/NEJM200101113440203; PUBMED: 11150359]CENTRAL
Stark AR, Carlo WA, Vohr BR, Papile L, Saha S, Bauer CR, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Death or neurodevelopmental impairment at 18 to 22 months corrected age in a randomized trial of early dexamethasone to prevent death or chronic lung disease in extremely low birth weight infants. Journal of Pediatrics2014; Vol. 164, issue 1:34‐9 e2. [DOI: 10.1016/j.jpeds.2013.07.027; PUBMED: 23992673]CENTRAL

Subhedar 1997 {published data only}

Subhedar NV. Personal communication. email2002. CENTRAL
Subhedar NV, Bennett AJ, Wardle SP, Shaw NJ. More trials on early treatment with corticosteroids are needed. BMJ 2000;320(7239):941. [PUBMED: 10742018 ]CENTRAL
Subhedar NV, Ryan SW, Shaw NJ. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 1997;77(3):F185‐90. [PUBMED: 9462187]CENTRAL

Suske 1996 {published data only}

Suske G, Oestreich K, Varnholt V, Lasch P, Kachel W. Influence of early postnatal dexamethasone therapy on ventilator dependency in surfactant‐substituted preterm infants. Acta Paediatrica 1996;85(6):713‐8. [PUBMED: 8816210]CENTRAL

Tapia 1998 {published data only}

Tapia JL, Ramirez R, Cifuentes J, Fabres J, Hubner ME, Bancalari A, et al. The effect of early dexamethasone administration on bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome. Journal of Pediatrics 1998;132(1):48‐52. [PUBMED: 9469999]CENTRAL

Vento 2004 {published data only}

Vento G, Matassa PG, Zecca E, Tortorolo L, Martelli M, De Carolis MP, et al. Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants. Pharmacology 2004;71(3):113‐9. [DOI: 10.1159/000077444; PUBMED: 15161992]CENTRAL

Wang 1996 {published data only}

Wang JY, Yeh TF, Lin YC, Miyamura K, Holmskov U, Reid KB. Measurement of pulmonary status and surfactant protein levels during dexamethasone treatment of neonatal respiratory distress syndrome. Thorax 1996;51(9):907‐13. [PUBMED: 8984701]CENTRAL
Wang JY, Yeh TF, Lin YJ, Chen WY, Lin CH. Early postnatal dexamethasone therapy may lessen lung inflammation in premature infants with respiratory distress syndrome on mechanical ventilation. Pediatric Pulmonology 1997;23(3):193‐7. [PUBMED: 9094727]CENTRAL

Watterberg 1999 {published data only}

Watterberg KL. Personal communication. email2002. CENTRAL
Watterberg KL, Gerdes JS, Gifford KL, Lin HM. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants. Pediatrics 1999;104(6):1258‐63. [PUBMED: 10585975]CENTRAL

Watterberg 2004 {published data only}

Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 2004;114(6):1649‐57. [DOI: 10.1542/peds.2004‐1159; PUBMED: 15574629]CENTRAL
Watterberg KL, Shaffer ML, Mishefske MJ, Leach CL, Mammel MC, Couser RJ, et al. Growth and neurodevelopmental outcomes after early low‐dose hydrocortisone treatment in extremely low birth weight infants. Pediatrics 2007;120(1):40‐8. [DOI: 10.1542/peds.2006‐3158; PUBMED: 17606560]CENTRAL

Yeh 1990 {published data only}

Yeh TF, Torre JA, Rastogi A, Anyebuno MA, Pildes RS. Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: a double‐blind, controlled study. Journal of Pediatrics 1990;117(2 Pt 1):273‐82. [PUBMED: 2199642]CENTRAL

Yeh 1997 {published data only}

Lin YJ, Lin CH, Wu JM, Tsai WH, Yeh TF. The effects of early postnatal dexamethasone therapy on pulmonary outcome in premature infants with respiratory distress syndrome: a two‐year follow‐up study. Acta Paediatrica 2005;94(3):310‐6. [PUBMED: 16028649]CENTRAL
Lin YJ, Yeh TF, Lin HC, Wu JM, Lin CH, Yu CY. Effects of early postnatal dexamethasone therapy on calcium homeostasis and bone growth in preterm infants with respiratory distress syndrome. Acta Paediatrica 1998;87(10):1061‐5. [PUBMED: 9825973]CENTRAL
Peng CT, Lin HC, Lin YJ, Tsai CH, Yeh TF. Early dexamethasone therapy and blood cell count in preterm infants. Pediatrics 1999;104(3 Pt 1):476‐81. [PUBMED: 10469772]CENTRAL
Yeh TF, Lin I, Shieh W, Lin H, Chen J, Kao S. Prevention of chronic lung disease (CLD) in premature RDS infants with early and prolonged dexamethasone (D) therapy ‐ a multicenter double‐blind controlled study. Pediatric Research 1994;35(4):262A. CENTRAL
Yeh TF, Lin YJ, Hsieh WS, Lin HC, Lin CH, Chen JY, et al. Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicenter clinical trial. Pediatrics 1997;100(4):E3. [PUBMED: 9310536]CENTRAL
Yeh TF, Lin YJ, Huang CC, Chen YJ, Lin CH, Lin HC, et al. Early dexamethasone therapy in preterm infants: a follow‐up study. Pediatrics 1998;101(5):E7. [PUBMED: 9565440]CENTRAL
Yeh TF, Lin YJ, Lin HC, Huang CC, Hsieh WS, Lin CH, et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. New England Journal of Medicine 2004;350(13):1304‐13. [DOI: 10.1056/NEJMoa032089; PUBMED: 15044641]CENTRAL

Ariagno 1987 {unpublished data only}

Ariagno RL, Sweeney TE, Baldwin RB, Inguillo D, Martin D. Controlled trial of dexamethasone in preterm infants at risk for bronchopulmonary dysplasia: lung function, clinical course and outcome at three years (as supplied 2000). Data on file. CENTRAL
Ariagno RL, Sweeney TJ, Baldwin RB, Inguillo D, Martin D. Dexamethasone effects on lung function and risks in 3 week old ventilatory dependent preterm infants. American Reviews of Respiratory Disease 1987;135:A125. CENTRAL

Avery 1985 {published data only}

Avery GB, Fletcher AB, Kaplan M, Brudno DS. Controlled trial of dexamethasone in respirator‐dependent infants with bronchopulmonary dysplasia. Pediatrics 1985;75(1):106‐11. [PUBMED: 3880879]CENTRAL

Brozanski 1995 {published data only}

Brozanski BS, Jones JG, Gilmour CH, Balsan MJ, Vazquez RL, Israel BA, et al. Effect of pulse dexamethasone therapy on the incidence and severity of chronic lung disease in the very low birth weight infant. Journal of Pediatrics 1995;126(5 Pt 1):769‐76. [PUBMED: 7752005]CENTRAL
Gilmour CH, Sentipal‐Walerius JM, Jones JG, Doyle JM, Brozanski BS, Balsan MJ, et al. Pulse dexamethasone does not impair growth and body composition of very low birth weight infants. Journal of the American College of Nutrition 1995;14(5):455‐62. [PUBMED: 8522724]CENTRAL
Hofkosh D, Brozanski BS, Edwards DE, Williams LA, Jones JG, Cheng KP. One year outcome of infants treated with pulse dexamethasone for prevention of BPD. Pediatric Research 1995;37(4):259A. CENTRAL

CDTG 1991 {published data only}

Collaborative Dexamethasone Trial Group. Dexamethasone therapy in neonatal chronic lung disease: an international placebo‐controlled trial. Pediatrics 1991;88(3):421‐7. [PUBMED: 1881718]CENTRAL
Jones R, Wincott E, Elbourne D, Grant A. Controlled trial of dexamethasone in neonatal chronic lung disease: a 3‐year follow‐up. Pediatrics 1995;96(5 Pt 1):897‐906. [PUBMED: 7478833]CENTRAL
Jones RA, Collaborative Dexamethasone Trial Follow‐up Group. Randomized, controlled trial of dexamethasone in neonatal chronic lung disease: 13‐ to 17‐year follow‐up study: I. Neurologic, psychological, and educational outcomes. Pediatrics 1995;116(2):370‐8. [DOI: 10.1542/peds.2004‐1818; PUBMED: 16061591]CENTRAL
Jones RA, Collaborative Dexamethasone Trial Follow‐up Group. Randomized, controlled trial of dexamethasone in neonatal chronic lung disease: 13‐ to 17‐year follow‐up study: II. Respiratory status, growth, and blood pressure. Pediatrics 2005;116(2):379‐84. [DOI: 10.1542/peds.2004‐1819; PUBMED: 16061592]CENTRAL

Cummings 1989 {published data only}

Cummings JJ. Personal communication. email2002. CENTRAL
Cummings JJ, D'Eugenio DB, Gross SJ. A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. New England Journal of Medicine 1989;320(23):1505‐10. [DOI: 10.1056/NEJM198906083202301; PUBMED: 2657423]CENTRAL
Gross SJ, Anbar RD, Mettelman BB. Follow‐up at 15 years of preterm infants from a controlled trial of moderately early dexamethasone for the prevention of chronic lung disease. Pediatrics 2005;115(3):681‐7. [DOI: 10.1542/peds.2004‐0956; PUBMED: 15741372]CENTRAL

Dobryansky 2012 {published data only}

Dobryansky D, Borysiuk O, Salabay Z, Dubrovna Y. Clinical effectiveness of early administration of caffeine and low‐dose hydrocortisone to preterm newborns with a high risk of BPD development. Archives of Disease in Childhood 2012;97:A119. [DOI: 10.1136/archdischild‐2012‐302724.0405]CENTRAL

Doyle 2006 {published data only}

Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB. Low‐dose dexamethasone facilitates extubation among chronically ventilator‐dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics 2006;117(1):75‐83. [PUBMED: 16396863]CENTRAL
Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, DART Study Investigators. Outcome at 2 years of age of infants from the DART study: a multicenter, international, randomized, controlled trial of low‐dose dexamethasone. Pediatrics 2007;119(4):716‐21. [DOI: 10.1542/peds.2006‐2806; PUBMED: 17403842 ]CENTRAL

Durand 1995 {published data only}

Durand M, Sardesai S, McEvoy C. Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial. Pediatrics 1995;95(4):584‐90. [PUBMED: 7700763]CENTRAL

Gaissmaier 1999 {published data only}

Gaissmaier RE, Pohlandt F. Single‐dose dexamethasone treatment of hypotension in preterm infants. Journal of Pediatrics 1999;134(6):701‐5. [PUBMED: 10356137]CENTRAL

Gross 2005 {published data only}

Gross SJ, Anbar RD, Mettelman BB. Follow‐up at 15 years of preterm infants from a controlled trial of moderately early dexamethasone for the prevention of chronic lung disease. Pediatrics 2005;115(3):681‐7. [10.1542/peds.2004‐0956; PUBMED: 15741372]CENTRAL

Harkavy 1989 {published data only}

Harkavy KL, Scanlon JW, Chowdhry PK, Grylack LJ. Dexamethasone therapy for chronic lung disease in ventilator‐ and oxygen‐dependent infants: a controlled trial. Journal of Pediatrics 1989;115(6):979‐83. [PUBMED: 2685220]CENTRAL

Kari 1993 {published data only}

Kari MA, Heinonen K, Ikonen RS, Koivisto M, Raivio KO. Dexamethasone treatment in preterm infants at risk for bronchopulmonary dysplasia. Archives of Disease in Childhood 1993;68(5 Spec No):566‐9. [PUBMED: 8323356]CENTRAL
Kari MA, Raivio KO, Venge P, Hallman M. Dexamethasone treatment of infants at risk for chronic lung disease: surfactant components and inflammatory parameters in airway specimens. Pediatric Research 1994;36(3):387‐93. [DOI: 10.1203/00006450‐199409000‐00020; PUBMED: 7808837]CENTRAL
Mieskonen S, Eronen M, Malmberg LP, Turpeinen M, Kari MA, Hallman M. Controlled trial of dexamethasone in neonatal chronic lung disease: an 8‐year follow‐up of cardiopulmonary function and growth. Acta Paediatrica 2003;92(8):896‐904. [PUBMED: 12948063]CENTRAL

Kazzi 1990 {published data only}

Kazzi NJ, Brans YW, Poland RL. Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation. Pediatrics 1990;86(5):722‐7. [PUBMED: 2235226]CENTRAL

Kothadia 1999 {published data only}

Bensky AS, Kothadia JM, Covitz W. Cardiac effects of dexamethasone in very low birth weight infants. Pediatrics 1996;97(6 Pt 1):818‐21. [PUBMED: 8657520]CENTRAL
Goldstein DJ, Waldrep EL, VanPelt JC, O'Shea TM. Developmental outcome at 5 years following dexamethasone use for very low birth weight infants. Pediatric Research 2000;47(4):310A. CENTRAL
Kothadia JM, O'Shea TM, Roberts D, Auringer ST, Weaver RG, Dillard RG. Randomized placebo‐controlled trial of a 42‐day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants. Pediatrics 1999;104(1 Pt 1):22‐7 Erratum in: Pediatrics 2004; 114(6):1746. [PUBMED: 10390255]CENTRAL
Nixon PA, Washburn LK, Schechter MS, O'Shea TM. Follow‐up study of a randomized controlled trial of postnatal dexamethasone therapy in very low birth weight infants: effects on pulmonary outcomes at age 8 to 11 years. Journal of Pediatrics 2007;150(4):345‐50. [DOI: 10.1016/j.jpeds.2006.12.013; PUBMED: 17382108]CENTRAL
O'Shea TM, Goldstein DJ, Jackson BG, Kothadia JM, Dillard RG. Randomized trial of a 42‐day tapering course of dexamethasone in very low birth weight infants: neurological, medical and functional outcome at 5 years of age. Pediatric Research 2000;47(4):319A. CENTRAL
O'Shea TM, Kothadia JM, Klinepeter KL, Goldstein DJ, Jackson BG, Weaver RG, et al. Randomized placebo‐controlled trial of a 42‐day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1‐year adjusted age. Pediatrics 1999;104(1 Pt 1):15‐21. [PUBMED: 10390254]CENTRAL
Washburn LK, Nixon PA, O'Shea TM. Follow‐up of a randomized, placebo‐controlled trial of postnatal dexamethasone: blood pressure and anthropometric measurements at school age. Pediatrics 2006;118(4):1592‐9. [DOI: 10.1542/peds.2006‐0973; PUBMED: 17015551]CENTRAL

Kovacs 1998 {published data only}

Kovacs L, Davis GM, Faucher D, Papageorgiou A. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Acta Paediatrica 1998;87(7):792‐8. [PUBMED: 9722255]CENTRAL

Noble‐Jamieson 1989 {published data only}

Noble‐Jamieson CM, Regev R, Silverman M. Dexamethasone in neonatal chronic lung disease: pulmonary effects and intracranial complications. European Journal of Pediatrics 1989;148(4):365‐7. [PUBMED: 2651132]CENTRAL

Ohlsson 1992 {published data only}

Ohlsson A, Calvert SA, Hosking M, Shennan AT. Randomized controlled trial of dexamethasone treatment in very‐low‐birth‐weight infants with ventilator‐dependent chronic lung disease. Acta Paediatrica 1992;81(10):751‐6. [PUBMED: 1421877]CENTRAL

Papile 1998 {published data only}

Papile LA, Tyson JE, Stoll BJ, Wright LL, Donovan EF, Bauer CR, et al. A multicenter trial of two dexamethasone regimens in ventilator‐dependent premature infants. New England Journal of Medicine 1998;338(16):1112‐8. [DOI: 10.1056/NEJM199804163381604; PUBMED: 9545359]CENTRAL
Stoll BJ, Temprosa M, Tyson JE, Papile LA, Wright LL, Bauer CR, et al. Dexamethasone therapy increases infection in very low birth weight infants. Pediatrics 1999;104(5):e63. [PUBMED: 10545589]CENTRAL

Parikh 2013 {published data only}

Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator‐dependent extremely preterm infants: effects on regional brain volumes. Journal of Pediatrics 2013;162(4):685‐90. [DOI: 10.1016/j.jpeds.2012.09.054; PUBMED: 23140612]CENTRAL

Romagnoli 1997 {published data only}

Romagnoli C, Vento G, Zecca E, Tortorolo G, Papacci P, De Carolis M, et al. Dexamethasone for the prevention of chronic lung disease in preterm neonates: a prospective randomized study [II desametazone nella prevenzione della patologia polmonare cronica del neonato pretermine: studio prospettico randomizzato]. Rivista Italiana di Pediatria [Italian Journal of Pediatrics] 1997;24:283‐8. CENTRAL
Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G. A three year follow up of preterm infants after moderately early treatment with dexamethasone. Archives of Disease in Childhood. Fetal and Neonatal Edition 2002;87(1):F55‐8. [12091294]CENTRAL
Romagnoli C, Zecca E, Vento G, Maggio L, Papacci P, Tortorolo G. Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized trial. Pharmacology 1999;59(5):266‐74. [PUBMED: 10529659]CENTRAL

Salas 2014 {published data only}

Salas G, Travaglianti M, Leone A, Couceiro C, Rodríguez S, Fariña D. Hydrocortisone for the treatment of refractory hypotension:a randomised controlled trial [Hidrocortisona para el tratamiento de hipotensión refractaria: ensayo clínico controlado y aleatorizado]. Anales de Pediatria (Barcelona, Spain : 2003) 2014;80(6):387‐93. [DOI: 10.1016/j.anpedi.2013.08.004; PUBMED: 24139558]CENTRAL

Scott 1997 {published data only}

Scott SM, Backstrom C, Bessman S. Effect of five days of dexamethasone therapy on ventilator dependence and adrenocorticotropic hormone‐stimulated cortisol concentrations. Journal of Perinatology 1997;17(1):24‐8. [PUBMED: 9069060]CENTRAL

Smolkin 2014 {published data only}

Smolkin T, Ulanovsky I, Jubran H, Blazer S, Makhoul IR. Experience with oral betamethasone in extremely low birthweight infants with bronchopulmonary dysplasia. Archives of Disease in Childhood. Fetal and Neonatal Edition 2014;99(6):F517‐8. [DOI: 10.1136/archdischild‐2014‐306619; PUBMED: 25074982]CENTRAL

Tsukahara 1999 {published data only}

Tsukahara H, Watanabe Y, Yasutomi M, Kobata R, Tamura S, Kimura K, et al. Early (4‐7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants. Biology of the Neonate 1999;76(5):283‐90. [DOI: 14170; PUBMED: 10516395]CENTRAL

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Vincer MJ, Allen AC. Double blind randomized controlled trial of 6‐day pulse of dexamethasone for very low birth weight infants (VLBW <1500 grams) who are ventilator dependent at 4 weeks of age. Pediatric Research 1998;43:201A. CENTRAL

Walther 2003 {published data only}

Walther FJ, Findlay RD, Durand M. Adrenal suppression and extubation rate after moderately early low‐dose dexamethasone therapy in very preterm infants. Early Human Development 2003;74(1):37‐45. [PUBMED: 14512180]CENTRAL

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Yaseen H, Okash I, Hanif M, al‐Umran K, al‐Faraidy A. Early dexamethasone treatment in preterm infants treated with surfactant: a double blind controlled trial. Journal of Tropical Pediatrics 1999;45(5):304‐6. [DOI: 10584476]CENTRAL

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Arias‐Camison JM, Lau J, Cole CH, Frantz ID. Meta‐analysis of dexamethasone therapy started in the first 15 days of life for prevention of chronic lung disease in premature infants. Pediatric Pulmonology 1999;28(3):167‐74. [PUBMED: 10495332]

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Doyle LW, Davis PG. Postnatal corticosteroids in preterm infants: systematic review of effects on mortality and motor function. Journal of Paediatrics and Child Health 2000;36(2):101‐7. [PUBMED: 10760004]

Doyle 2010a

Doyle LW, Ehrenkranz RA, Halliday HL. Postnatal hydrocortisone for preventing or treating bronchopulmonary dysplasia in preterm infants: a systematic review. Neonatology 2010;98(2):111‐7. [DOI: 10.1159/000279992; PUBMED: 20150750]

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Doyle 2017

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Onland 2017

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Papile LA, Stoll B, Donovan E, Tyson I, Bauer C, Wright L, et al. Dexamethasone therapy in infants at risk for chronic lung disease (CLD): a multicenter, randomized, double‐masked trial. Pediatric Research 1996;39:236A.

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Van Goudoever JB, Wattimena JD, Carnielli VP, Sulkers EJ, Degenhart HJ, Sauer PJ. Effect of dexamethasone on protein metabolism in infants with bronchopulmonary dysplasia. Journal of Pediatrics 1994;124(1):112‐8. [PUBMED: 8283359]

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Werner JC, Sicard RE, Hansen TWR, Solomon E, Cowett RM, Oh W. Hypertrophic cardiomyopathy associated with dexamethasone therapy for bronchopulmonary dysplasia. Journal of Pediatrics 1992;120(2 Pt 1):286‐91. [PUBMED: 1735831]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Anttila 2005

Methods

Multi‐centre double‐blind placebo‐controlled randomised trial

Participants

109 infants with birth weight 500 grams to 999 grams, gestation < 32 weeks, need for mechanical ventilation and supplemental oxygen by 4 hours of age. Stratified by weight (500 grams to 749 grams vs 750 grams to 999 grams)
Exclusions: life‐threatening congenital anomalies or known chromosomal anomaly

Interventions

4 doses of dexamethasone 0.25 mg/kg each at 12‐hourly intervals or normal saline as placebo. First dose was given before 6 hours. Open‐label dexamethasone was allowed when deemed necessary by attending physician, but its use was discouraged.

Outcomes

Survival to 36 weeks without IVH (grade III to IV), PVL (echodensities after first week or periventricular cysts on ultrasound), or BPD (oxygen at 36 weeks); growth, duration of assisted ventilation and oxygen, late corticosteroid treatment, infection, hyperglycaemia, hypertension, ROP, PDA, GI bleeding and perforation, NEC

Notes

This paper also reported a meta‐analysis of early short vs early prolonged dexamethasone treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation by coded vials prepared in the pharmacy at each centre

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified primary and secondary outcomes reported

Baden 1972

Methods

Double‐blind placebo‐controlled randomised trial

Participants

44 preterm infants < 24 hours old with respiratory distress confirmed both clinically and radiologically

Interventions

Hydrocortisone 25 mg/kg on admission and 12 hours later intravenously
Control group given placebo

Outcomes

Death, FiO2, cortisol levels, and blood gases

Notes

The oldest study, carried out in 1972. Used hydrocortisone in a very short course of treatment

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation via random numbers and sealed envelopes

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Batton 2012

Methods

Multi‐centre randomised placebo‐controlled trial

Participants

Infants at 23 to 26 completed weeks' gestation with study‐defined low blood pressure

Interventions

Hydrocortisone 1 mg/kg loading, then 0.5 mg/kg at 12‐hourly intervals for 6 doses

Outcomes

Short‐term outcomes during primary hospitalisation of death, BPD (not defined), IVH grade III or IV, PVL, and NEC requiring surgery

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Enrolled infants were randomised from a prespecified sequence, allocated by centre, and received treatment from an investigational pharmacist.

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Unclear risk

Primary outcome of the study was to determine the feasibility of a randomised trial of blood pressure management, rather than effects on bronchopulmonary dysplasia.

Baud 2016

Methods

Multi‐centre double‐blind randomised controlled trial

Participants

523 inborn infants at 24 to 27 weeks’ gestational age in the first 24 hours after birth recruited from 21 French centres with NICU facilities between 25 May 2008 and 31 January 2014.

Exclusions: rupture of membranes at < 22 weeks’ gestation; birth weight < third centile according to French sex‐customised curves; severe perinatal asphyxia (Apgar score = 0–3 for longer than 5 minutes, cord blood pH < 7·00, or both) and expected to die shortly after birth; congenital malformations (birth defects or major structural abnormalities detectable prenatally); known chromosomal aberrations

Interventions

Hydrocortisone hemisuccinate 1 mg/kg/d divided into 2 doses for 7 days, then 0.5 mg/kg/d once per day for 3 days (total dose 8.5 mg/kg)

Control infants were given an equivalent volume of 5% glucose placebo.

Open‐label corticosteroids were not allowed during first 10 days of treatment.

Outcomes

Short‐term primary outcome: survival free of bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age. BPD was diagnosed at 36 weeks (± 3 days) without additional testing if an infant required mechanical ventilation, non‐invasive ventilation with continuous positive airway pressure, or 30% or more supplemental oxygen concentration. BPD was diagnosed in infants requiring only 22% to 29% oxygen if the oxygen requirement was confirmed by a standardised oxygen‐reduction test, which was completed by neonatologists masked to treatment groups.

Secondary outcomes: bronchopulmonary dysplasia at 36 weeks’ postmenstrual age; death; surgical ligation of patent ductus arteriosus; air leaks; pulmonary haemorrhage; insulin requirement; late‐onset sepsis (positive blood culture or symptomatic pneumonia); necrotising enterocolitis, gastrointestinal perforation; grade 3 or 4 IVH; cystic PVL; death before discharge; severe retinopathy of prematurity (requiring laser treatment or surgery)

Longer term: Children were assessed at approximately 22 months’ corrected age. Children underwent a French‐based developmental assessment that was standardised in the mid‐1990s, and a standardised neurodevelopmental assessment based on the Amiel‐Tison and Denver scales. Neurodevelopmental impairment (NDI) was defined as any disability on the standardised neurodevelopmental assessment, cerebral palsy, blindness, deafness, or a formal developmental assessment score < ‐1 SD (< 85).

Notes

Study was stopped early because of lack of funding, rather than because any predetermined threshold had been reached, at approximately 2/3 of projected sample size of 786.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly assigned (1:1) via a secure study website

Strata for 24 to 25 weeks and 26 to 27 weeks

Allocation concealment (selection bias)

Low risk

Remote electronic allocation

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding maintained by identical placebo

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessors blinded to knowledge of treatment group at both primary hospitalisation phase and 22‐month follow‐up phase

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Low risk for short‐term outcomes, as all but 2 randomised participants have short‐term outcomes reported. However, moderate risk at follow‐up phase because although 93% (379/406) of long‐term survivors were assessed at 22 months’ corrected age, only 75% (304/406) had full neurological and developmental assessment.

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes reported

Biswas 2003

Methods

Multi‐centre placebo‐controlled randomised trial

Participants

253 infants < 30 weeks' gestation, within 9 hours of birth at entry; all mechanically ventilated

Interventions

Hydrocortisone 1 mg/kg/d as continuous infusion for 5 days, then 0.5 mg/kg/d for 2 days. Also given tri‐iodothyronine 6 µg/kg/d for 5 days, halving to 3 µg/kg/d for 2 days
Controls given equal volume infusion of 5% dextrose

Outcomes

Primary outcome was death or ventilator dependence at 7 days, or death or oxygen dependence at 14 days.
Secondary outcomes included duration of ventilation, oxygen dependence, and hospitalisation; oxygen dependency at 36 weeks; IVH, PVL, PDA, and NEC

Notes

Hydrocortisone combined with T3 infusion

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by Oxford Perinatal Trials Unit

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Bonsante 2007

Methods

Two‐centre randomised double‐blind placebo‐controlled trial

Participants

70 infants with birth weight < 1000 grams or < 28 weeks' gestation, ventilator‐dependent after 7 days of age, and considered to be a candidate for corticosteroids
Exclusions: major anomaly likely to affect long‐term neurological outcome

Interventions

Active treatment – total dose of hydrocortisone 10.5 mg/kg over 10 days
Placebo group ‐ equal volume of 0.9% saline

Outcomes

Primary outcomes: survival free of disability at 2 years of age, mortality up to 2 years of age, and neurological outcome after discharge
Secondary outcomes: rate of BPD, death or BPD, failure to extubate, other complications during primary hospital stay including GI perforation, severe IVH (grade 3 or 4) and cystic PVL, long‐term neurosensory impairment (blindness, deafness, developmental delay assessed by MDI on Bayley Scales, cerebral palsy), and disabilities (severe ‐ any of severe cerebral palsy (not likely to walk), blindness, or severe developmental delay (MDI < 55), moderate‐moderate cerebral palsy (not walking at 2 years but likely to do so), deafness, moderate developmental delay (MDI 55 to < 70), mild‐mild cerebral palsy (walking at 2 years), or mild developmental delay (MDI 70 to < 85)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation centrally

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessment blind: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up reporting: yes for outcomes during primary hospital stay ‐ 98% of surviving infants traced to 2 years of age

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Efird 2005

Methods

Randomised double‐blind placebo‐controlled trial

Participants

34 infants of gestation > 23 weeks and < 29 weeks, and birth weight > 500 grams and < 1000 grams enrolled by 2 hours of age
Exclusions: major malformations, chromosomal abnormalities, congenital heart disease

Interventions

Hydrocortisone intravenously at dose of 1 mg/kg every 12 hours for 2 days, followed by 0.3 mg/kg every 12 hours for 3 days
Control infants received an equivalent volume of normal saline as placebo

Outcomes

Blood pressure, urine output, hyperglycaemia, mortality, durations of mechanical ventilation and hospital stay, BPD (oxygen at 36 weeks), infection, NEC, intestinal perforation, PDA, IVH, PVL, cortisol levels

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation via sequentially numbered, preassigned treatment designations in sealed, opaque envelopes

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Garland 1999

Methods

Multi‐centre placebo‐controlled randomised trial

Participants

241 infants weighing between 500 grams and 1500 grams, received surfactant, at significant risk for BPD or death using a model to predict at 24 hours

Interventions

3‐Day course of dexamethasone beginning at 24 to 48 hours. First 2 doses were 0.4 mg/kg, third and fourth doses 0.2 mg/kg, and fifth and sixth doses 0.1 mg/kg and 0.05 mg/kg, respectively. Dexamethasone dose reduced slightly after first interim analysis (see Notes)
Similar volume of normal saline was given to control infants

Outcomes

Primary outcomes were survival without BPD defined as oxygen therapy at 36 weeks to maintain SaO2 above 91% and mortality.
Secondary outcomes included duration of ventilation and supplemental oxygen, respiratory support at 28 days of life, length of stay for survivors, use of subsequent dexamethasone therapy, and usual complications of prematurity.

Notes

At first interim analysis (n = 75), increased risk of GI perforation was noted in the dexamethasone group. Data Monitoring Committee recommended reducing the dexamethasone dose to 4 doses of 0.25 mg/kg/dose every 12 hours begun at 24 to 48 hours, followed by doses of 0.125 mg/kg and 0.05 mg/kg at the next two 12‐hour periods, respectively.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by study pharmacists at each centre

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Halac 1990

Methods

Placebo‐controlled randomised trial

Participants

248 infants, birth weight ≤ 1500 grams, gestation < 34 weeks, with evidence of "birth asphyxia" (1‐minute Apgar score < 5, prolonged resuscitation, and metabolic acidosis (HCO3 < 15 mmol/L within 1 hour of birth))

Interventions

7‐Day course of dexamethasone 1 mg/kg 12‐hourly beginning on first day of life

Outcomes

Neonatal mortality, mortality to discharge, NEC, PDA, sepsis, severe IVH

Notes

Possible exclusion of 5 deaths after randomisation, but not clear which group they came from

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation via list of random numbers

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

Primary prespecified outcome of NEC was reported, as were a large number of other outcomes.

Hochwald 2014

Methods

Placebo‐controlled randomised trial

Participants

22 infants, gestational age ≤ 30 weeks or birth weight ≤ 1250 grams, and < 48 hours after birth, with an arterial catheter in place, invasive mean blood pressure < gestational age on 3 consecutive measurements 10 minutes apart, and after treatment with 1 or 2 boluses of 10 mL of 0.9% saline. Excluded if blood loss, hydrops, or major cardiac lesions

Interventions

Hydrocortisone 7 mg/kg total over 48 hours, or equal volume of 0.9% saline placebo

Outcomes

Mortality (presumably to discharge), NEC, BPD, positive blood culture, insulin treatment

Notes

Major outcome was to determine whether hydrocortisone reduced vasopressor doses

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

Not stated

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Placebo‐controlled

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not stated

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Short‐term outcomes reported for all participants

Selective reporting (reporting bias)

Unclear risk

Only short‐term outcomes reported, but major outcome of effects on vasopressor doses not reported

Kopelman 1999

Methods

Two‐centre randomised placebo‐controlled trial

Participants

70 infants < 28 weeks' gestation requiring intermittent mandatory ventilation and arterial catheterisation

Interventions

Dexamethasone 0.2 mg/kg within 2 hours of delivery
Control infants given an equal volume of saline

Outcomes

Ventilation Index (VI), IMV rate, mean blood pressure, incidence of PDA, need for indomethacin, number extubated during first week, usual complications of RDS

Notes

After an interim analysis showed that the incidence of IVH was much lower than expected, enrolment was stopped and analysis was limited to a comparison of ventilator settings, blood pressure, and pressor use during first 7 days.
Outcome of successful extubation was available at only 1 hospital, where 38 infants were enrolled.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in the hospital pharmacy stratified by use of antenatal corticosteroids; exact method of randomisation not stated

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported, but others reported too

Lauterbach 2006

Methods

Three‐armed randomised controlled trial: (1) nebulised pentoxifylline, (2) intravenous dexamethasone, (3) nebulised water placebo

Participants

150 infants < 1500 grams birth weight who needed oxygen on fourth day of life, regardless of the need for assisted ventilation. Major malformations and grade 3 or 4 IVH led to exclusions.

Interventions

Dexamethasone 0.25 mg/kg/dose every 12 hours for 3 days

Outcomes

Primary endpoint BPD (oxygen dependency at 36 weeks). Secondary endpoints included PDA, IVH and PVL,

Notes

All prespecified outcomes reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation table

Allocation concealment (selection bias)

Unclear risk

Not clearly stated

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Unable to blind treatment groups for comparison of dexamethasone vs nebulised water placebo

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Unable to blind treatment groups for comparison of dexamethasone vs nebulised water placebo

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Short‐term outcomes reported for all participants

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Lin 1999

Methods

Placebo‐controlled randomised trial

Participants

40 infants of 500 grams to 1999 grams with severe RDS, needing IPPV within 6 hours of birth

Interventions

Dexamethasone 0.25 mg/kg 12‐hourly from 1 to 7 days, 0.12 mg/kg 12‐hourly from 8 to 14 days, 0.05 mg/kg 12‐hourly from 15 to 21 days, 0.02 mg/kg 12‐hourly from 22 to 28 days
Saline placebo was given to controls.

Outcomes

Mortality at 28 days; discharge, failure to extubate (during study), death or BPD (36 weeks), BPD (28 days and 36 weeks), infection (clinical), severe IVH, plasma glucose, mean blood pressure on days 2, 5, 7, and 16; weight at 2 weeks

Notes

Sequential analysis for 12 pairs. Data given for 40 infants as randomised into the 2 groups

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in a paired sequential trial. Assignment determined by pharmacist and groups stratified by birth weight: 500 grams to 999 grams, 1000 grams to 1500 grams, and 1501 grams to 1999 grams. Allocation by drawing lots

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Mukhopadhyay 1998

Methods

Single‐centre randomised controlled trial

Participants

19 infants < 34 weeks and < 2000 grams who could be provided with ventilation. Clinical and radiographic evidence of RDS; IPPV with oxygen > 30%

Interventions

Dexamethasone 0.5 mg/kg/dose 12‐hourly for 3 days starting within 6 hours of birth
Control group did not receive any drug

Outcomes

Changes in oxygen requirements, mean duration of ventilation, culture‐positive sepsis, PDA, BPD (not defined), pneumothorax, mortality

Notes

Infants were entered into the trial only if a ventilator was available. Surfactant was not given.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation: method not stated

Allocation concealment (selection bias)

Unclear risk

Allocation concealment: not sure

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of intervention: no

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Blinding of outcome measurement: no

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Ng 2006

Methods

Double‐blind randomised controlled trial

Participants

48 infants of gestation < 32 weeks and birth weight < 1500 grams who had systemic hypotension despite treatment with volume expanders and dopamine within the first 7 days of life Infants also had to have an indwelling arterial catheter for continuous BP monitoring.
Exclusions: major or lethal congenital or chromosomal abnormalities, congenital heart defects, previous postnatal systemic or inhaled corticosteroids, proven infection, NEC

Interventions

Hydrocortisone 1 mg/kg every 8 hours for 5 days
Control infants received isotonic saline as placebo for 5 days.

Outcomes

BP, use of vasopressors, duration of ventilation, oxygen and hospital stay, PIE, pulmonary haemorrhage, pneumothorax, hyperglycaemia, glycosuria, IVH (grade III or IV), PVL, NEC, GI perforation, sepsis, ROP (> stage II), mortality

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation in blocks of 6 by computer‐generated random numbers and opening numbered, sealed, opaque envelopes

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

Primary outcome was blood pressure, which was reported.

Peltoniemi 2005

Methods

Multi‐centre double‐blind randomised controlled trial

Participants

51 infants with birth weight 501 grams to 1250 grams, gestation 23 to 30 weeks, needing mechanical ventilation before the age of 24 hours. The subgroup 1000 grams to 1250 grams had to need supplemental oxygen and mechanical ventilation > 24 hours despite surfactant.

Exclusions: lethal malformations, suspected chromosomal abnormalities

Interventions

Hydrocortisone 2.0 mg/kg/d intravenously 8‐hourly for 2 days, 1.5 mg/kg/d 8‐hourly for 2 days, 0.75 mg/kg/d 12‐hourly for 6 days
Control infants received isotonic saline as placebo. First dose was given before 36 hours. Use of open‐label corticosteroids was discouraged.

Outcomes

Survival without BPD (oxygen at 36 weeks), IVH (grades III or IV), cystic PVL, durations of ventilation, oxygen and hospital stay, sepsis, hyperglycaemia, hypertension, PDA, GI bleeding, GI perforation, NEC, ROP, and cortisol levels

Long‐term outcomes: At 2 years ‐ neurosensory impairments (blindness, deafness, developmental delay assessed by MDI on Bayley Scales, cerebral palsy) and disabilities (severe ‐ any of severe cerebral palsy (not likely to walk), blindness, or severe developmental delay (MDI < 55, moderate‐moderate cerebral palsy (not walking at 2 years but likely to do so), deafness, moderate developmental delay (MDI 55 to < 70), mild‐mild cerebral palsy (walking at 2 years), or mild developmental delay (MDI 70 to < 85). Follow‐up rate was 87% (40/46).

At 6 years ‐ IQ (Wechsler Preschool and Primary Scale of Intelligence ‐ Revised) and language (Reynell Developmental Language Scale III) were assessed, as were diagnoses of cerebral palsy, blindness, and deafness. Follow‐up rate was 80% (37 of the 46 survivors).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation at each centre via identical coded syringes. Exact method of randomisation not stated. Stratified by birth weight (501 grams to 750 grams vs 750 grams to 999 grams vs 1000 grams to 1250 grams)

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes (for primary hospital outcomes). Follow‐up rates at 2 and 6 years listed above

Selective reporting (reporting bias)

Low risk

Primary outcome was reported as specified.

Rastogi 1996

Methods

Double‐blind randomised controlled trial

Participants

70 preterm infants < 12 hours old, weighing 700 grams to 1500 grams with respiratory distress syndrome (RDS) confirmed clinically and radiologically; infants needed mechanical ventilation > 30% O2 and/or MAP 7 cmH2O a/A < 0.25 after surfactant treatment.
Exclusions: major malformations, chromosome abnormalities, severe infection, Apgar < 3 at 5 minutes

Interventions

Intravenous dexamethasone 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.15 mg/kg/d for 3 days, 0.05 mg/kg/d for 3 days
Control group given saline placebo

Outcomes

FiO2, MAP, BPD (28 days and CXR), severe BPD (36 weeks), duration O2, infections, deaths, pneumothorax, pulmonary haemorrhage, PDA, IVH, NEC, hyperglycaemia, insulin use, hypertension, ROP

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation: via a pharmacy list; stratified for birth weight

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Romagnoli 1999

Methods

Randomised non‐blinded controlled trial

Participants

50 infants < 1251 grams or < 33 weeks, oxygen‐dependent at 72 hours, and at high risk of BPD according to a scoring system predicting 90% risk of BPD

Interventions

Dexamethasone 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, and 0.125 mg/kg/d for 1 day
Control group: no mention of placebo

Outcomes

Survival to 28 days, survival to discharge, PDA, IVH (grades 3 and 4), PVL, sepsis, NEC, ROP (stages III and above), requiring ventilation at 28 days, BPD at 28 days and 36 weeks, hyperglycaemia, hypertension, needed late corticosteroids, growth failure, left ventricular hypertrophy

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation via random numbers, concealed in numbered sealed envelopes

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of intervention: no

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Blinding of outcome measurements: no

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Sanders 1994

Methods

Randomised double‐blind controlled trial

Participants

40 infants < 30 weeks' gestation and 12 to 18 hours old with RDS, both clinical and radiological. Infants were treated with mechanical ventilation and surfactant
Exclusions: sepsis, congenital heart disease, chromosome abnormalities, need for exchange transfusion

Interventions

Dexamethasone 0.5 mg/kg twice, 12 hours apart
Control group given saline placebo

Outcomes

MAP, FiO2, mortality, extubation < 7 days, pulmonary function tests, duration IPPV, O2, hospital, mortality, BPD (36 weeks O2), late corticosteroids

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in the pharmacy via sealed envelopes. Method of randomisation not described

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

Prespecified outcomes reported, but definitions vague

Shinwell 1996

Methods

Multi‐centre double‐blind randomised controlled trial

Participants

248 preterm infants with birth weight 500 grams to 2000 grams, 1 to 3 days old, requiring mechanical ventilation with more than 40% oxygen
Exclusions: active bleeding, hypertension, hyperglycaemia, active infection, lethal congenital anomalies

Interventions

Intravenous dexamethasone 0.25 mg/kg every 12 hours 6 times
Controls given saline placebo

Outcomes

Mortality, survival with no O2, mechanical ventilation at 3 and 7 days, BPD, duration in hospital, IVH, PVL, pneumothorax, PIE, PDA, sepsis, hypertension, hyperglycaemia

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation, stratified by centre and birth weight, from random numbers list in the pharmacy

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes for short‐term; 84% for long‐term

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Sinkin 2000

Methods

Multi‐centre randomised double‐blind trial

Participants

384 infants < 30 weeks' gestation with RDS by clinical and radiographic signs, needing IPPV at 12 to 18 hours of age; had received at least 1 dose of surfactant

Interventions

Dexamethasone 0.5 mg/kg at 12 to 18 hours of age, second dose 12 hours later
Control group given an equal volume of placebo

Outcomes

Primary outcomes were survival, survival without oxygen at 28 days or 36 weeks, and survival without oxygen at 28 days or 36 weeks and without late corticosteroids
Length of time in oxygen, on ventilation, to regain birth weight, and in hospital. Hyperglycaemia, hypertension, IVH, PDA, sepsis, NEC, isolated GI perforation, ROP, air leak, discharged home on oxygen

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in the pharmacy via labelled syringes. Stratification by centre. Exact method of randomisation not stated

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Soll 1999

Methods

Multi‐centre randomised double‐blind trial

Participants

542 infants weighing 501 grams to 1000 grams who required assisted ventilation < 12 hours, had received surfactant by 12 hours, were physiologically stable, and had no life‐threatening congenital anomalies

Interventions

Dexamethasone 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.10 mg/kg/d for 3 days, and 0.05 mg/kg/d for 3 days. Control infants received a similar volume of normal saline.
Infants in either group could receive late postnatal corticosteroids beginning on day 14 if they were on assisted ventilation with supplemental oxygen > 30%.

Outcomes

Primary outcome was BPD or death at 36 weeks' adjusted age.
Secondary outcome measures included clinical status at 14 days and 28 days, duration of assisted ventilation, supplemental oxygen and hospital stay, treatment with late postnatal corticosteroids, proven sepsis, hypertension and hyperglycaemia requiring therapy, weight at 36 weeks, usual complications of prematurity

Notes

Published as an extended abstract and presented at a clinical meeting

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in hospital pharmacies by opening opaque, sealed envelopes. Precise method of randomisation not stated

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Stark 2001

Methods

Multi‐centre randomised double‐blind trial

Participants

220 infants with birth weight 501 grams to 1000 grams, mechanically ventilated < 12 hours. Infants > 750 grams also needed to receive surfactant and have FiO2 > 0.29.

Interventions

Dexamethasone 0.15 mg/kg/d for 3 days, then tapered over 7 days
Saline placebo

Outcomes

Death or BPD, oxygen at 28 days, PIE, late corticosteroid treatment, hypertension, hyperglycaemia, GI perforation

Notes

Factorial design; infants also randomised to routine ventilator management or a strategy of minimal ventilator support to reduce mechanical lung injury. After enrolling 220 infants (sample size estimate was 1200), the trial was halted owing to unanticipated adverse events.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation via numbers generated by a random, permuted block algorithm, stratified by birth weight

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Subhedar 1997

Methods

Randomised controlled trial ‐ factorial design

Participants

42 preterm infants, entry at 96 hours if gestation < 32 weeks, mechanical ventilation from birth, surfactant treatment, and high risk of developing BPD based on score (Ryan 1996)
Exclusion criteria: major congenital anomaly, structural cardiac defect, significant ductus shunting, culture‐positive sepsis, IVH with parenchymal involvement, pulmonary or GI haemorrhage, abnormal coagulation, thrombocytopenia (platelets < 50,000)

Interventions

Intravenous dexamethasone at 12‐hourly intervals for 6 days; 0.5 mg/kg/dose for 6 doses and 0.25 mg/kg/dose for a further 6 doses. Inhaled NO 5 to 20 ppm for 72 hours
Control groups were not given placebo

Outcomes

Mortality, BPD at 28 days and > 36 weeks with abnormal chest radiograph
Duration of ventilation, time to extubation, duration of hospitalisation, maximum grade of IVH, pulmonary haemorrhage, pneumothorax, severe PDA, NEC, ROP (stage 3 or 4)
Complications including ileal perforation, upper GI haemorrhage, hyperglycaemia, hypertension, septicaemia

Notes

Note factorial design, which means that half of treated infants and half of control infants also received 72 hours of inhaled NO

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation by computer‐generated random numbers and sealed envelopes. Factorial design provided 4 groups: early dexamethasone, inhaled NO, both drugs together, and neither drug.

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of intervention: no

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Blinding of outcome measurements: no

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Unclear risk

All prespecified outcomes reported

Suske 1996

Methods

Randomised controlled trial

Participants

26 preterm infants < 2 hours old, with birth weight < 1500 grams if FiO2 > 0.50, or > 1500 grams birth weight with FiO2 > 0.70

Exclusions: known sepsis, cardiac anomalies, malformations of lung or CNS

Interventions

Intravenous dexamethasone 0.5 mg/kg/d for 5 days
Controls were not given placebo.

Outcomes

Blood gases, ventilator settings, mortality IVH, BPD (O2 28 days), NEC, late sepsis, PDA, ROP, air leak, duration in hospital

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation via sealed envelopes. Randomisation achieved by drawing lots

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding of intervention: no

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Blinding of outcome measurement: no

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Tapia 1998

Methods

Multi‐centre double‐blind placebo‐controlled randomised trial

Participants

113 (4 exclusions for congenital abnormality, early sepsis, and failure to obtain follow‐up data) infants with birth weight between 700 and 1600 grams, clinical and radiological diagnosis of RDS, needing mechanical ventilation, and < 36 hours of age
Exclusion criteria: life‐threatening congenital malformation or chromosome abnormality, strong suspicion of infection at birth (maternal chorioamnionitis) or early sepsis (positive blood culture in the first 36 hours of life)

Interventions

Intravenous dexamethasone 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.12 mg/kg/d for 3 days, and 0.06 mg/kg/d for 3 days
Placebo group received an equivalent volume of saline solution.

Outcomes

Primary outcomes were death before hospital discharge, BPD (oxygen need at 28 days and x‐ray changes), death or BPD, and oxygen need at 36 weeks.
Other outcomes included time on ventilator, time in over 40% oxygen, and time in oxygen.
Major morbidity and complications included pneumothorax, PIE, PDA, pulmonary haemorrhage, pneumonia, sepsis, NEC, ROP, hypertension, hyperglycaemia, and IVH (grades I to II and III to IV).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation via ampoules of dexamethasone and saline prepared in the hospital pharmacy. Exact method of randomisation not described

Allocation concealment (selection bias)

Low risk

Blinding of randomisation: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: almost (109/113)

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Vento 2004

Methods

Randomised controlled trial

Participants

20 infants with birth weight < 1251 grams and gestation < 33 weeks who were oxygen‐ and ventilator‐dependent on fourth day of life and were at high risk of BPD by study authors' own scoring system
Exclusions: none stated

Interventions

Intravenous dexamethasone 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, and 0.125 mg/kg/d for 1 day (total dose 2.375 mg/kg)
Control group received no corticosteroid treatment.

Outcomes

Tracheal aspirates for cell counts, pulmonary mechanics, PDA, IVH (grades III and IV), extubation during study period

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation but method not stated

Allocation concealment (selection bias)

Unclear risk

Allocation concealment: uncertain

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding of intervention: uncertain

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome measurement: uncertain

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Wang 1996

Methods

Double‐blind randomised controlled trial

Participants

63 infants with birth weight from 1000 grams to 1999 grams, AGA, clinical and radiographic RDS, IPPV (0 to 12, age after birth)

Interventions

Dexamethasone 0.25 mg/kg 12‐hourly from 1 to 7 days, 0.125 mg/kg 12‐hourly from 8 to 14 days, 0.05 mg/kg 12‐hourly from 15 to 21 days. First dose administered at < 12 hours
Controls received saline placebo.

Outcomes

Oxygen requirements; PCO2; MAP; SP‐A and SP‐D in tracheal aspirate; failure to extubate by third day, 7th day, 14th day, and 28th day; mortality before discharge; sepsis; BPD at 28 days

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in a double‐blind fashion; method not stated

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Watterberg 1999

Methods

Two‐centre double‐blind randomised controlled trial

Participants

40 infants weighing between 500 grams and 999 grams who were AGA and needed mechanical ventilation < 48 hours of age
Exclusion criteria: maternal diabetes, congenital sepsis, SGA

Interventions

Hydrocortisone 1.0 mg/kg/d every 12 hours for 9 days, 0.5 mg/kg/d for 3 days
Control infants were given an equal volume of normal saline.

Outcomes

Primary outcome was survival without supplemental oxygen at 36 weeks' post conception.
Secondary outcomes among survivors: BPD at 36 weeks, duration of mechanical ventilation, > 40% oxygen, > 25% oxygen, hospital stay, weight and head circumference at 36 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation at each centre by constant block design with 4 participants per block to minimise bias over time. Separate randomisation tables were used for infants exposed to antenatal corticosteroids.

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Watterberg 2004

Methods

Multi‐centre double‐blind randomised controlled trial

Participants

360 infants of 500 grams to 999 grams birth weight, needing mechanical ventilation, aged 12 to 48 hours
Exclusions: major congenital anomaly, congenital sepsis, postnatal corticosteroids, triplet or higher‐order gestation

Interventions

Hydrocortisone 1 mg/kg/d 12‐hourly for 12 days, then 0.5 mg/kg/d for 3 days
Control group infants received an equal volume of normal saline placebo.

Outcomes

Survival without BPD (oxygen at 36 weeks), physiological BPD, death before 36 weeks, death before discharge, BPD in survivors, durations of mechanical ventilation and oxygen, hospital stay, weight and OFC at 36 weeks, PDA, infection, NEC, GI perforation, major IVH (grade 3 or 4), cystic PVL, ROP, and open‐label corticosteroid therapy
Longer‐term outcomes included neurosensory impairments (any of cerebral palsy, blindness, deafness, or developmental or motor delay, as assessed by Bayley Scales (MDI or PDI, respectively)).

Notes

Sample size estimate was 712, but the study was stopped early because of increased incidence of apparently spontaneous GI perforation in the hydrocortisone group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random allocation, stratified by centre and birth weight (500 grams to 749 grams vs 750 grams to 999 grams), via a permuted block scheme with blocks of 6 in each stratum. Randomisation lists in each pharmacy in a sealed envelope

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: yes

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Yeh 1990

Methods

Double‐blind randomised controlled trial

Participants

57 preterm infants weighing between 700 grams and 1999 grams, < 13 hours old, with severe RDS both clinically and radiologically. They needed mechanical ventilation < 4 hours and were excluded if they had infection.

Interventions

Intravenous dexamethasone 0.50 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.12 mg/kg/d for 3 days, 0.05 mg/kg/d for 3 days
Control infants were given saline placebo.

Outcomes

MAP, FiO2, pulmonary function tests, BP, glucose, mortality, BPD, duration O2, hospital, weight loss, sepsis, PDA, IVH (> grade I), ROP

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation in blocks of 10 via a pharmacy list. Exact method of randomisation not described

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurements: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: almost

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

Yeh 1997

Methods

Multi‐centre double‐blind randomised controlled trial

Participants

262 infants of birth weight < 2000 grams with RDS and requiring mechanical ventilation after birth

Interventions

Dexamethasone 0.25 mg/kg/dose every 12 hours intravenously on days 1 to 7; 0.12 mg/kg/dose every 12 hours intravenously from days 8 to 14; 0.05 mg/kg/dose every 12 hours intravenously from days 15 to 21; and 0.02 mg/kg/dose every 12 hours intravenously from days 22 to 28
Control infants were given saline placebo.

Outcomes

BPD judged at 28 days or at 36 weeks
Extubation during the study, mortality, bacteraemia or clinical sepsis, and side effects of hyperglycaemia, hypertension, cardiac hypertrophy, hyperparathyroidism, and growth failure

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation via central pharmacy random number list; exact method of randomisation not described

Allocation concealment (selection bias)

Low risk

Allocation concealment: yes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding of intervention: yes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinding of outcome measurement: yes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete follow‐up: almost for short‐term; 81% for long‐term

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported

ACTH: adrenocorticotrophic hormone.
ABA: appropriate for gestational age.
BP: blood pressure.
BPD: bronchopulmonary dysplasia.
CLD: chronic lung disease.
CNS: central nervous system.
CXR: chest x‐ray.
FiO2: fraction of inspired oxygen.
GI: gastrointestinal.
HCO3: bicarbonate.
IMV: intermittent mandatory ventilation.
IPPV: intermittent positive‐pressure ventilation.
IVH: intraventricular haemorrhage.
MAP: mean airway pressure.
MDI: Mental Developmental Index.
NDI: neurodevelopmental impairment.
NEC: necrotising enterocolitis.
NO: nitric oxide.
NRN: Neonatal Research Network.
O2: oxygen.
OFC: occipito‐frontal circumference.
PDA: patent ductus arteriosus.
PDI: Psychomotor Developmental Index.
PIE: pulmonary interstitial emphysema.
ppm: parts per million.
PVL: periventricular leukomalacia.
RDS: respiratory distress syndrome.
ROP: retinopathy of prematurity.
SaO2: oxygen saturation.
SGA: small for gestational age.
SP‐A: surfactant protein‐A.
SP‐D: surfactant protein‐D.
T3: triiodothyronine.
VI: Ventilation Index.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Ariagno 1987

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Avery 1985

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Brozanski 1995

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

CDTG 1991

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Cummings 1989

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Dobryansky 2012

20 VLBW infants were randomised to both hydrocortisone and caffeine as active treatments, compared with "standard guidelines", which presumably meant no hydrocortisone or caffeine. Major outcomes reported included BPD and BPD combined with death. As caffeine reduces BPD (Schmidt 2006), the independent effect of hydrocortisone cannot be determined.

Doyle 2006

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Durand 1995

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Gaissmaier 1999

Primary outcome was need for an epinephrine infusion 12 hours after treatment. No long‐term outcomes reported

Gross 2005

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Harkavy 1989

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Kari 1993

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Kazzi 1990

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Kothadia 1999

Study of late postnatal corticosteroids included in the review "'Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Kovacs 1998

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Noble‐Jamieson 1989

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Ohlsson 1992

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Papile 1998

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Parikh 2013

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Romagnoli 1997

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Salas 2014

Recruited term infants only for a study of early hydrocortisone to treat hypotension

Scott 1997

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Smolkin 2014

Before after study only ‐ not an RCT

Tsukahara 1999

Not an RCT; 26 study infants and 12 historical controls

Vincer 1998

Study of late postnatal corticosteroids included in the review "'Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Walther 2003

Study of late postnatal corticosteroids included in the review "Late (> 7 days) systemic postnatal corticosteroids for bronchopulmonary dysplasia in preterm infants" (Doyle 2017)

Yaseen 1999

Study of early dexamethasone, but no outcomes relevant to this review were reported

BPD: bronchopulmonary dysplasia.
RCT: randomised controlled trial.
VLBW: very low birth weight.

Data and analyses

Open in table viewer
Comparison 1. Mortality

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality (up to 28 days) Show forest plot

19

2950

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.88, 1.19]

Analysis 1.1

Comparison 1 Mortality, Outcome 1 Neonatal mortality (up to 28 days).

Comparison 1 Mortality, Outcome 1 Neonatal mortality (up to 28 days).

1.1 Dexamethasone

16

2603

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.90, 1.24]

1.2 Hydrocortisone

3

347

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.50, 1.23]

2 Mortality at 36 weeks Show forest plot

20

3733

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.89, 1.14]

Analysis 1.2

Comparison 1 Mortality, Outcome 2 Mortality at 36 weeks.

Comparison 1 Mortality, Outcome 2 Mortality at 36 weeks.

2.1 Dexamethasone

14

2487

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.94, 1.25]

2.2 Hydrocortisone

6

1246

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.65, 1.06]

3 Mortality to hospital discharge Show forest plot

30

4273

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.85, 1.07]

Analysis 1.3

Comparison 1 Mortality, Outcome 3 Mortality to hospital discharge.

Comparison 1 Mortality, Outcome 3 Mortality to hospital discharge.

3.1 Dexamethasone

19

2840

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.90, 1.18]

3.2 Hydrocortisone

11

1433

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.65, 0.98]

4 Mortality at latest reported age Show forest plot

31

4373

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.85, 1.06]

Analysis 1.4

Comparison 1 Mortality, Outcome 4 Mortality at latest reported age.

Comparison 1 Mortality, Outcome 4 Mortality at latest reported age.

4.1 Dexamethasone

20

2940

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.90, 1.16]

4.2 Hydrocortisone

11

1433

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.65, 0.99]

Open in table viewer
Comparison 2. Bronchopulmonary dysplasia (BPD)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 BPD (28 days of life) Show forest plot

17

2874

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.93]

Analysis 2.1

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 1 BPD (28 days of life).

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 1 BPD (28 days of life).

1.1 Dexamethasone

16

2621

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.79, 0.92]

1.2 Hydrocortisone

1

253

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.85, 1.18]

2 BPD (36 weeks' postmenstrual age) Show forest plot

24

3929

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.72, 0.87]

Analysis 2.2

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 2 BPD (36 weeks' postmenstrual age).

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 2 BPD (36 weeks' postmenstrual age).

2.1 Dexamethasone

16

2584

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.62, 0.81]

2.2 Hydrocortisone

8

1345

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.80, 1.05]

3 BPD at 36 weeks' postmenstrual age in survivors Show forest plot

21

2970

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.74, 0.88]

Analysis 2.3

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 3 BPD at 36 weeks' postmenstrual age in survivors.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 3 BPD at 36 weeks' postmenstrual age in survivors.

3.1 Dexamethasone

14

1917

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.64, 0.83]

3.2 Hydrocortisone

7

1053

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.80, 1.03]

4 Late rescue with corticosteroids Show forest plot

14

2483

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.68, 0.82]

Analysis 2.4

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 4 Late rescue with corticosteroids.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 4 Late rescue with corticosteroids.

4.1 Dexamethasone

10

1974

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.65, 0.80]

4.2 Hydrocortisone

4

509

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.73, 1.40]

5 Survivors who had late rescue with corticosteroids Show forest plot

7

895

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.67, 0.89]

Analysis 2.5

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 5 Survivors who had late rescue with corticosteroids.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 5 Survivors who had late rescue with corticosteroids.

5.1 Dexamethasone

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.68, 0.91]

5.2 Hydrocortisone

1

42

Risk Ratio (M‐H, Fixed, 95% CI)

0.48 [0.24, 0.98]

6 Survivors discharged home on oxygen Show forest plot

6

691

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.51, 1.03]

Analysis 2.6

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 6 Survivors discharged home on oxygen.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 6 Survivors discharged home on oxygen.

6.1 Dexamethasone

3

406

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.48, 1.26]

6.2 Hydrocortisone

3

285

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.40, 1.11]

Open in table viewer
Comparison 3. Death or bronchopulmonary dysplasia (BPD)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death or BPD at 28 days of life Show forest plot

15

2546

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.88, 0.96]

Analysis 3.1

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 1 Death or BPD at 28 days of life.

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 1 Death or BPD at 28 days of life.

1.1 Dexamethasone

14

2293

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.86, 0.96]

1.2 Hydrocortisone

1

253

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.90, 1.12]

2 Death or BPD at 36 weeks' postmenstrual age Show forest plot

25

3960

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.83, 0.93]

Analysis 3.2

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 2 Death or BPD at 36 weeks' postmenstrual age.

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 2 Death or BPD at 36 weeks' postmenstrual age.

2.1 Dexamethasone

16

2581

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.80, 0.94]

2.2 Hydrocortisone

9

1379

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

Open in table viewer
Comparison 4. Failure to extubate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure to extubate by third day Show forest plot

4

887

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.75, 0.95]

Analysis 4.1

Comparison 4 Failure to extubate, Outcome 1 Failure to extubate by third day.

Comparison 4 Failure to extubate, Outcome 1 Failure to extubate by third day.

1.1 Dexamethasone

3

381

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.62, 0.86]

1.2 Hydrocortisone

1

506

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.82, 1.14]

2 Failure to extubate by seventh day Show forest plot

8

1448

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.68, 0.85]

Analysis 4.2

Comparison 4 Failure to extubate, Outcome 2 Failure to extubate by seventh day.

Comparison 4 Failure to extubate, Outcome 2 Failure to extubate by seventh day.

2.1 Dexamethasone

6

703

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.61, 0.84]

2.2 Hydrocortisone

2

745

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.69, 0.94]

3 Failure to extubate by 14th day Show forest plot

4

443

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.62, 0.97]

Analysis 4.3

Comparison 4 Failure to extubate, Outcome 3 Failure to extubate by 14th day.

Comparison 4 Failure to extubate, Outcome 3 Failure to extubate by 14th day.

4 Failure to extubate by 28th day Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.72, 0.98]

Analysis 4.4

Comparison 4 Failure to extubate, Outcome 4 Failure to extubate by 28th day.

Comparison 4 Failure to extubate, Outcome 4 Failure to extubate by 28th day.

Open in table viewer
Comparison 5. Complications during primary hospitalisation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Infection Show forest plot

25

4101

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.96, 1.15]

Analysis 5.1

Comparison 5 Complications during primary hospitalisation, Outcome 1 Infection.

Comparison 5 Complications during primary hospitalisation, Outcome 1 Infection.

1.1 Dexamethasone

18

2821

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.91, 1.15]

1.2 Hydrocortisone

7

1280

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.94, 1.25]

2 Hyperglycaemia Show forest plot

13

2167

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [1.20, 1.47]

Analysis 5.2

Comparison 5 Complications during primary hospitalisation, Outcome 2 Hyperglycaemia.

Comparison 5 Complications during primary hospitalisation, Outcome 2 Hyperglycaemia.

2.1 Dexamethasone

12

2117

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [1.21, 1.49]

2.2 Hydrocortisone

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.50, 1.67]

3 Hypertension Show forest plot

11

1993

Risk Ratio (M‐H, Fixed, 95% CI)

1.85 [1.54, 2.22]

Analysis 5.3

Comparison 5 Complications during primary hospitalisation, Outcome 3 Hypertension.

Comparison 5 Complications during primary hospitalisation, Outcome 3 Hypertension.

3.1 Dexamethasone

10

1943

Risk Ratio (M‐H, Fixed, 95% CI)

1.84 [1.53, 2.21]

3.2 Hydrocortisone

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.33, 26.92]

4 Hypertrophic cardiomyopathy Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

4.33 [1.40, 13.37]

Analysis 5.4

Comparison 5 Complications during primary hospitalisation, Outcome 4 Hypertrophic cardiomyopathy.

Comparison 5 Complications during primary hospitalisation, Outcome 4 Hypertrophic cardiomyopathy.

5 Growth failure Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

6.67 [2.27, 19.62]

Analysis 5.5

Comparison 5 Complications during primary hospitalisation, Outcome 5 Growth failure.

Comparison 5 Complications during primary hospitalisation, Outcome 5 Growth failure.

6 Pulmonary air leak Show forest plot

16

3225

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.74, 1.13]

Analysis 5.6

Comparison 5 Complications during primary hospitalisation, Outcome 6 Pulmonary air leak.

Comparison 5 Complications during primary hospitalisation, Outcome 6 Pulmonary air leak.

6.1 Dexamethasone

12

2041

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.66, 1.08]

6.2 Hydrocortisone

4

1184

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.75, 1.65]

7 Patent ductus arteriosus (PDA) Show forest plot

24

4013

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.72, 0.85]

Analysis 5.7

Comparison 5 Complications during primary hospitalisation, Outcome 7 Patent ductus arteriosus (PDA).

Comparison 5 Complications during primary hospitalisation, Outcome 7 Patent ductus arteriosus (PDA).

7.1 Dexamethasone

17

2706

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.69, 0.84]

7.2 Hydrocortisone

7

1307

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.71, 0.95]

8 Severe IVH Show forest plot

26

4103

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.83, 1.11]

Analysis 5.8

Comparison 5 Complications during primary hospitalisation, Outcome 8 Severe IVH.

Comparison 5 Complications during primary hospitalisation, Outcome 8 Severe IVH.

8.1 Dexamethasone

17

2736

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.81, 1.14]

8.2 Hydrocortisone

9

1367

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.74, 1.23]

9 Severe intraventricular haemorrhage (IVH) in infants examined Show forest plot

7

1909

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.11]

Analysis 5.9

Comparison 5 Complications during primary hospitalisation, Outcome 9 Severe intraventricular haemorrhage (IVH) in infants examined.

Comparison 5 Complications during primary hospitalisation, Outcome 9 Severe intraventricular haemorrhage (IVH) in infants examined.

10 Periventricular leukomalacia (PVL) Show forest plot

15

2807

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.78, 1.46]

Analysis 5.10

Comparison 5 Complications during primary hospitalisation, Outcome 10 Periventricular leukomalacia (PVL).

Comparison 5 Complications during primary hospitalisation, Outcome 10 Periventricular leukomalacia (PVL).

10.1 Dexamethasone

8

1514

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.84, 1.81]

10.2 Hydrocortisone

7

1293

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.46, 1.40]

11 PVL in infants with cranial ultrasound scans Show forest plot

7

1841

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.79, 1.60]

Analysis 5.11

Comparison 5 Complications during primary hospitalisation, Outcome 11 PVL in infants with cranial ultrasound scans.

Comparison 5 Complications during primary hospitalisation, Outcome 11 PVL in infants with cranial ultrasound scans.

12 PVL in survivors seen at follow‐up Show forest plot

2

183

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.60, 2.48]

Analysis 5.12

Comparison 5 Complications during primary hospitalisation, Outcome 12 PVL in survivors seen at follow‐up.

Comparison 5 Complications during primary hospitalisation, Outcome 12 PVL in survivors seen at follow‐up.

13 Necrotising enterocolitis (NEC) Show forest plot

25

4050

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.11]

Analysis 5.13

Comparison 5 Complications during primary hospitalisation, Outcome 13 Necrotising enterocolitis (NEC).

Comparison 5 Complications during primary hospitalisation, Outcome 13 Necrotising enterocolitis (NEC).

13.1 Dexamethasone

15

2661

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.69, 1.13]

13.2 Hydrocortisone

10

1389

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.66, 1.37]

14 Gastrointestinal bleeding Show forest plot

12

1816

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.35, 2.55]

Analysis 5.14

Comparison 5 Complications during primary hospitalisation, Outcome 14 Gastrointestinal bleeding.

Comparison 5 Complications during primary hospitalisation, Outcome 14 Gastrointestinal bleeding.

14.1 Dexamethasone

10

1725

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.35, 2.58]

14.2 Hydrocortisone

2

91

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.27, 8.74]

15 Gastrointestinal perforation Show forest plot

16

3040

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.02, 0.05]

Analysis 5.15

Comparison 5 Complications during primary hospitalisation, Outcome 15 Gastrointestinal perforation.

Comparison 5 Complications during primary hospitalisation, Outcome 15 Gastrointestinal perforation.

15.1 Dexamethasone

9

1936

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.01, 0.05]

15.2 Hydrocortisone

7

1104

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.00, 0.06]

16 Pulmonary haemorrhage Show forest plot

10

1820

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.87, 1.54]

Analysis 5.16

Comparison 5 Complications during primary hospitalisation, Outcome 16 Pulmonary haemorrhage.

Comparison 5 Complications during primary hospitalisation, Outcome 16 Pulmonary haemorrhage.

16.1 Dexamethasone

7

686

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.65, 1.45]

16.2 Hydrocortisone

3

1134

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.92, 2.03]

17 Any retinopathy of prematurity (ROP) Show forest plot

9

1345

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.80, 0.97]

Analysis 5.17

Comparison 5 Complications during primary hospitalisation, Outcome 17 Any retinopathy of prematurity (ROP).

Comparison 5 Complications during primary hospitalisation, Outcome 17 Any retinopathy of prematurity (ROP).

17.1 Dexamethasone

8

1042

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.72, 0.99]

17.2 Hydrocortisone

1

303

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.04]

18 Severe ROP Show forest plot

14

2577

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.66, 0.98]

Analysis 5.18

Comparison 5 Complications during primary hospitalisation, Outcome 18 Severe ROP.

Comparison 5 Complications during primary hospitalisation, Outcome 18 Severe ROP.

18.1 Dexamethasone

8

1507

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.60, 0.99]

18.2 Hydrocortisone

6

1070

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.63, 1.21]

19 Severe ROP in survivors Show forest plot

12

1575

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.64, 0.94]

Analysis 5.19

Comparison 5 Complications during primary hospitalisation, Outcome 19 Severe ROP in survivors.

Comparison 5 Complications during primary hospitalisation, Outcome 19 Severe ROP in survivors.

19.1 Dexamethasone

10

1238

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.59, 0.95]

19.2 Hydrocortisone

2

337

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.60, 1.17]

Open in table viewer
Comparison 6. Long‐term follow‐up

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Bayley Mental Developmental Index (MDI) <‐2 SD Show forest plot

3

842

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.78, 1.29]

Analysis 6.1

Comparison 6 Long‐term follow‐up, Outcome 1 Bayley Mental Developmental Index (MDI) <‐2 SD.

Comparison 6 Long‐term follow‐up, Outcome 1 Bayley Mental Developmental Index (MDI) <‐2 SD.

2 Bayley MDI <‐2 SD in tested survivors Show forest plot

3

528

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.79, 1.25]

Analysis 6.2

Comparison 6 Long‐term follow‐up, Outcome 2 Bayley MDI <‐2 SD in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 2 Bayley MDI <‐2 SD in tested survivors.

3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD Show forest plot

3

842

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.85, 1.60]

Analysis 6.3

Comparison 6 Long‐term follow‐up, Outcome 3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD.

Comparison 6 Long‐term follow‐up, Outcome 3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD.

4 Bayley PDI <‐2 SD in tested survivors Show forest plot

3

528

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.87, 1.57]

Analysis 6.4

Comparison 6 Long‐term follow‐up, Outcome 4 Bayley PDI <‐2 SD in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 4 Bayley PDI <‐2 SD in tested survivors.

5 Developmental delay (criteria not specified) Show forest plot

1

248

Risk Ratio (M‐H, Fixed, 95% CI)

1.68 [1.08, 2.61]

Analysis 6.5

Comparison 6 Long‐term follow‐up, Outcome 5 Developmental delay (criteria not specified).

Comparison 6 Long‐term follow‐up, Outcome 5 Developmental delay (criteria not specified).

6 Developmental delay (criteria not specified) in tested survivors Show forest plot

1

159

Risk Ratio (M‐H, Fixed, 95% CI)

1.94 [1.30, 2.88]

Analysis 6.6

Comparison 6 Long‐term follow‐up, Outcome 6 Developmental delay (criteria not specified) in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 6 Developmental delay (criteria not specified) in tested survivors.

7 Blindness Show forest plot

8

939

Risk Ratio (M‐H, Fixed, 95% CI)

2.01 [0.74, 5.50]

Analysis 6.7

Comparison 6 Long‐term follow‐up, Outcome 7 Blindness.

Comparison 6 Long‐term follow‐up, Outcome 7 Blindness.

8 Blindness in survivors assessed Show forest plot

8

585

Risk Ratio (M‐H, Fixed, 95% CI)

2.16 [0.80, 5.86]

Analysis 6.8

Comparison 6 Long‐term follow‐up, Outcome 8 Blindness in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 8 Blindness in survivors assessed.

9 Deafness Show forest plot

8

721

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.39, 3.37]

Analysis 6.9

Comparison 6 Long‐term follow‐up, Outcome 9 Deafness.

Comparison 6 Long‐term follow‐up, Outcome 9 Deafness.

10 Deafness in survivors assessed Show forest plot

8

476

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.40, 3.29]

Analysis 6.10

Comparison 6 Long‐term follow‐up, Outcome 10 Deafness in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 10 Deafness in survivors assessed.

11 Cerebral palsy Show forest plot

13

1973

Risk Ratio (IV, Fixed, 95% CI)

1.42 [1.06, 1.91]

Analysis 6.11

Comparison 6 Long‐term follow‐up, Outcome 11 Cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 11 Cerebral palsy.

11.1 Dexamethasone

7

921

Risk Ratio (IV, Fixed, 95% CI)

1.75 [1.20, 2.55]

11.2 Hydrocortisone

6

1052

Risk Ratio (IV, Fixed, 95% CI)

1.05 [0.66, 1.66]

12 Death before follow‐up in trials assessing cerebral palsy Show forest plot

13

1973

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.78, 1.05]

Analysis 6.12

Comparison 6 Long‐term follow‐up, Outcome 12 Death before follow‐up in trials assessing cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 12 Death before follow‐up in trials assessing cerebral palsy.

12.1 Dexamethasone

7

921

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.81, 1.21]

12.2 Hydrocortisone

6

1052

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

13 Death or cerebral palsy Show forest plot

13

1973

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.91, 1.16]

Analysis 6.13

Comparison 6 Long‐term follow‐up, Outcome 13 Death or cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 13 Death or cerebral palsy.

13.1 Dexamethasone

7

921

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [1.00, 1.37]

13.2 Hydrocortisone

6

1052

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.71, 1.05]

14 Cerebral palsy in survivors assessed Show forest plot

13

1328

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [1.11, 1.90]

Analysis 6.14

Comparison 6 Long‐term follow‐up, Outcome 14 Cerebral palsy in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 14 Cerebral palsy in survivors assessed.

14.1 Dexamethasone

7

586

Risk Ratio (M‐H, Fixed, 95% CI)

1.82 [1.29, 2.57]

14.2 Hydrocortisone

6

742

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.65, 1.58]

15 Major neurosensory disability (variable criteria ‐ see individual studies) Show forest plot

7

1703

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.89, 1.33]

Analysis 6.15

Comparison 6 Long‐term follow‐up, Outcome 15 Major neurosensory disability (variable criteria ‐ see individual studies).

Comparison 6 Long‐term follow‐up, Outcome 15 Major neurosensory disability (variable criteria ‐ see individual studies).

15.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.03, 1.83]

15.2 Hydrocortisone

3

931

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.64, 1.14]

16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria) Show forest plot

6

1182

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.81, 1.17]

Analysis 6.16

Comparison 6 Long‐term follow‐up, Outcome 16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria).

16.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.82, 1.25]

16.2 Hydrocortisone

2

410

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.58, 1.28]

17 Death or major neurosensory disability (variable criteria) Show forest plot

7

1703

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.87, 1.08]

Analysis 6.17

Comparison 6 Long‐term follow‐up, Outcome 17 Death or major neurosensory disability (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 17 Death or major neurosensory disability (variable criteria).

17.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.99, 1.30]

17.2 Hydrocortisone

3

931

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.69, 0.97]

18 Major neurosensory disability in survivors examined (variable criteria) Show forest plot

8

1178

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.89, 1.28]

Analysis 6.18

Comparison 6 Long‐term follow‐up, Outcome 18 Major neurosensory disability in survivors examined (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 18 Major neurosensory disability in survivors examined (variable criteria).

18.1 Dexamethasone

4

469

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [1.05, 1.77]

18.2 Hydrocortisone

4

709

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.65, 1.10]

19 Abnormal neurological exam (variable criteria ‐ see individual studies) Show forest plot

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.33, 2.47]

Analysis 6.19

Comparison 6 Long‐term follow‐up, Outcome 19 Abnormal neurological exam (variable criteria ‐ see individual studies).

Comparison 6 Long‐term follow‐up, Outcome 19 Abnormal neurological exam (variable criteria ‐ see individual studies).

20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria) Show forest plot

6

1350

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.75, 1.07]

Analysis 6.20

Comparison 6 Long‐term follow‐up, Outcome 20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria).

20.1 Dexamethasone

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.79, 1.21]

20.2 Hydrocortisone

1

521

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.04]

21 Death or abnormal neurological exam (variable criteria) Show forest plot

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [1.06, 1.42]

Analysis 6.21

Comparison 6 Long‐term follow‐up, Outcome 21 Death or abnormal neurological exam (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 21 Death or abnormal neurological exam (variable criteria).

22 Abnormal neurological exam in tested survivors (variable criteria) Show forest plot

5

508

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [1.41, 2.52]

Analysis 6.22

Comparison 6 Long‐term follow‐up, Outcome 22 Abnormal neurological exam in tested survivors (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 22 Abnormal neurological exam in tested survivors (variable criteria).

23 Intellectual impairment (IQ < 70) Show forest plot

2

90

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [0.57, 3.31]

Analysis 6.23

Comparison 6 Long‐term follow‐up, Outcome 23 Intellectual impairment (IQ < 70).

Comparison 6 Long‐term follow‐up, Outcome 23 Intellectual impairment (IQ < 70).

24 Intellectual impairment (IQ < 70) in survivors assessed Show forest plot

2

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.47, 2.65]

Analysis 6.24

Comparison 6 Long‐term follow‐up, Outcome 24 Intellectual impairment (IQ < 70) in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 24 Intellectual impairment (IQ < 70) in survivors assessed.

25 "Major neurosensory impairment" ‐ blindness or deafness Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.25]

Analysis 6.25

Comparison 6 Long‐term follow‐up, Outcome 25 "Major neurosensory impairment" ‐ blindness or deafness.

Comparison 6 Long‐term follow‐up, Outcome 25 "Major neurosensory impairment" ‐ blindness or deafness.

26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.57 [0.16, 2.12]

Analysis 6.26

Comparison 6 Long‐term follow‐up, Outcome 26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed.

27 Behaviour abnormalities Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.25]

Analysis 6.27

Comparison 6 Long‐term follow‐up, Outcome 27 Behaviour abnormalities.

Comparison 6 Long‐term follow‐up, Outcome 27 Behaviour abnormalities.

28 Behaviour abnormalities in 3‐year‐old survivors assessed Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.22]

Analysis 6.28

Comparison 6 Long‐term follow‐up, Outcome 28 Behaviour abnormalities in 3‐year‐old survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 28 Behaviour abnormalities in 3‐year‐old survivors assessed.

29 Abnormal EEG Show forest plot

2

306

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.66, 2.33]

Analysis 6.29

Comparison 6 Long‐term follow‐up, Outcome 29 Abnormal EEG.

Comparison 6 Long‐term follow‐up, Outcome 29 Abnormal EEG.

30 Abnormal EEG in tested survivors Show forest plot

2

146

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.61, 2.08]

Analysis 6.30

Comparison 6 Long‐term follow‐up, Outcome 30 Abnormal EEG in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 30 Abnormal EEG in tested survivors.

31 Rehospitalisation in infancy Show forest plot

3

672

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.68, 1.08]

Analysis 6.31

Comparison 6 Long‐term follow‐up, Outcome 31 Rehospitalisation in infancy.

Comparison 6 Long‐term follow‐up, Outcome 31 Rehospitalisation in infancy.

32 Rehospitalisation in infancy in survivors Show forest plot

3

430

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.71, 1.07]

Analysis 6.32

Comparison 6 Long‐term follow‐up, Outcome 32 Rehospitalisation in infancy in survivors.

Comparison 6 Long‐term follow‐up, Outcome 32 Rehospitalisation in infancy in survivors.

Study flow diagram: review update.
Figuras y tablas -
Figure 1

Study flow diagram: review update.

Funnel plot of comparison: 1 Mortality, outcome: 1.4 Mortality at latest reported age.
Figuras y tablas -
Figure 2

Funnel plot of comparison: 1 Mortality, outcome: 1.4 Mortality at latest reported age.

Funnel plot of comparison: 2 Bronchopulmonary dysplasia (BPD), outcome: 2.2 BPD (36 weeks' postmenstrual age).
Figuras y tablas -
Figure 3

Funnel plot of comparison: 2 Bronchopulmonary dysplasia (BPD), outcome: 2.2 BPD (36 weeks' postmenstrual age).

Funnel plot of comparison: 3 Death or bronchopulmonary dysplasia (BPD), outcome: 3.2 Death or BPD at 36 weeks' postmenstrual age.
Figuras y tablas -
Figure 4

Funnel plot of comparison: 3 Death or bronchopulmonary dysplasia (BPD), outcome: 3.2 Death or BPD at 36 weeks' postmenstrual age.

Funnel plot of comparison: 6 Long‐term follow‐up, outcome: 6.11 Cerebral palsy.
Figuras y tablas -
Figure 5

Funnel plot of comparison: 6 Long‐term follow‐up, outcome: 6.11 Cerebral palsy.

Comparison 1 Mortality, Outcome 1 Neonatal mortality (up to 28 days).
Figuras y tablas -
Analysis 1.1

Comparison 1 Mortality, Outcome 1 Neonatal mortality (up to 28 days).

Comparison 1 Mortality, Outcome 2 Mortality at 36 weeks.
Figuras y tablas -
Analysis 1.2

Comparison 1 Mortality, Outcome 2 Mortality at 36 weeks.

Comparison 1 Mortality, Outcome 3 Mortality to hospital discharge.
Figuras y tablas -
Analysis 1.3

Comparison 1 Mortality, Outcome 3 Mortality to hospital discharge.

Comparison 1 Mortality, Outcome 4 Mortality at latest reported age.
Figuras y tablas -
Analysis 1.4

Comparison 1 Mortality, Outcome 4 Mortality at latest reported age.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 1 BPD (28 days of life).
Figuras y tablas -
Analysis 2.1

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 1 BPD (28 days of life).

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 2 BPD (36 weeks' postmenstrual age).
Figuras y tablas -
Analysis 2.2

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 2 BPD (36 weeks' postmenstrual age).

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 3 BPD at 36 weeks' postmenstrual age in survivors.
Figuras y tablas -
Analysis 2.3

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 3 BPD at 36 weeks' postmenstrual age in survivors.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 4 Late rescue with corticosteroids.
Figuras y tablas -
Analysis 2.4

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 4 Late rescue with corticosteroids.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 5 Survivors who had late rescue with corticosteroids.
Figuras y tablas -
Analysis 2.5

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 5 Survivors who had late rescue with corticosteroids.

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 6 Survivors discharged home on oxygen.
Figuras y tablas -
Analysis 2.6

Comparison 2 Bronchopulmonary dysplasia (BPD), Outcome 6 Survivors discharged home on oxygen.

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 1 Death or BPD at 28 days of life.
Figuras y tablas -
Analysis 3.1

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 1 Death or BPD at 28 days of life.

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 2 Death or BPD at 36 weeks' postmenstrual age.
Figuras y tablas -
Analysis 3.2

Comparison 3 Death or bronchopulmonary dysplasia (BPD), Outcome 2 Death or BPD at 36 weeks' postmenstrual age.

Comparison 4 Failure to extubate, Outcome 1 Failure to extubate by third day.
Figuras y tablas -
Analysis 4.1

Comparison 4 Failure to extubate, Outcome 1 Failure to extubate by third day.

Comparison 4 Failure to extubate, Outcome 2 Failure to extubate by seventh day.
Figuras y tablas -
Analysis 4.2

Comparison 4 Failure to extubate, Outcome 2 Failure to extubate by seventh day.

Comparison 4 Failure to extubate, Outcome 3 Failure to extubate by 14th day.
Figuras y tablas -
Analysis 4.3

Comparison 4 Failure to extubate, Outcome 3 Failure to extubate by 14th day.

Comparison 4 Failure to extubate, Outcome 4 Failure to extubate by 28th day.
Figuras y tablas -
Analysis 4.4

Comparison 4 Failure to extubate, Outcome 4 Failure to extubate by 28th day.

Comparison 5 Complications during primary hospitalisation, Outcome 1 Infection.
Figuras y tablas -
Analysis 5.1

Comparison 5 Complications during primary hospitalisation, Outcome 1 Infection.

Comparison 5 Complications during primary hospitalisation, Outcome 2 Hyperglycaemia.
Figuras y tablas -
Analysis 5.2

Comparison 5 Complications during primary hospitalisation, Outcome 2 Hyperglycaemia.

Comparison 5 Complications during primary hospitalisation, Outcome 3 Hypertension.
Figuras y tablas -
Analysis 5.3

Comparison 5 Complications during primary hospitalisation, Outcome 3 Hypertension.

Comparison 5 Complications during primary hospitalisation, Outcome 4 Hypertrophic cardiomyopathy.
Figuras y tablas -
Analysis 5.4

Comparison 5 Complications during primary hospitalisation, Outcome 4 Hypertrophic cardiomyopathy.

Comparison 5 Complications during primary hospitalisation, Outcome 5 Growth failure.
Figuras y tablas -
Analysis 5.5

Comparison 5 Complications during primary hospitalisation, Outcome 5 Growth failure.

Comparison 5 Complications during primary hospitalisation, Outcome 6 Pulmonary air leak.
Figuras y tablas -
Analysis 5.6

Comparison 5 Complications during primary hospitalisation, Outcome 6 Pulmonary air leak.

Comparison 5 Complications during primary hospitalisation, Outcome 7 Patent ductus arteriosus (PDA).
Figuras y tablas -
Analysis 5.7

Comparison 5 Complications during primary hospitalisation, Outcome 7 Patent ductus arteriosus (PDA).

Comparison 5 Complications during primary hospitalisation, Outcome 8 Severe IVH.
Figuras y tablas -
Analysis 5.8

Comparison 5 Complications during primary hospitalisation, Outcome 8 Severe IVH.

Comparison 5 Complications during primary hospitalisation, Outcome 9 Severe intraventricular haemorrhage (IVH) in infants examined.
Figuras y tablas -
Analysis 5.9

Comparison 5 Complications during primary hospitalisation, Outcome 9 Severe intraventricular haemorrhage (IVH) in infants examined.

Comparison 5 Complications during primary hospitalisation, Outcome 10 Periventricular leukomalacia (PVL).
Figuras y tablas -
Analysis 5.10

Comparison 5 Complications during primary hospitalisation, Outcome 10 Periventricular leukomalacia (PVL).

Comparison 5 Complications during primary hospitalisation, Outcome 11 PVL in infants with cranial ultrasound scans.
Figuras y tablas -
Analysis 5.11

Comparison 5 Complications during primary hospitalisation, Outcome 11 PVL in infants with cranial ultrasound scans.

Comparison 5 Complications during primary hospitalisation, Outcome 12 PVL in survivors seen at follow‐up.
Figuras y tablas -
Analysis 5.12

Comparison 5 Complications during primary hospitalisation, Outcome 12 PVL in survivors seen at follow‐up.

Comparison 5 Complications during primary hospitalisation, Outcome 13 Necrotising enterocolitis (NEC).
Figuras y tablas -
Analysis 5.13

Comparison 5 Complications during primary hospitalisation, Outcome 13 Necrotising enterocolitis (NEC).

Comparison 5 Complications during primary hospitalisation, Outcome 14 Gastrointestinal bleeding.
Figuras y tablas -
Analysis 5.14

Comparison 5 Complications during primary hospitalisation, Outcome 14 Gastrointestinal bleeding.

Comparison 5 Complications during primary hospitalisation, Outcome 15 Gastrointestinal perforation.
Figuras y tablas -
Analysis 5.15

Comparison 5 Complications during primary hospitalisation, Outcome 15 Gastrointestinal perforation.

Comparison 5 Complications during primary hospitalisation, Outcome 16 Pulmonary haemorrhage.
Figuras y tablas -
Analysis 5.16

Comparison 5 Complications during primary hospitalisation, Outcome 16 Pulmonary haemorrhage.

Comparison 5 Complications during primary hospitalisation, Outcome 17 Any retinopathy of prematurity (ROP).
Figuras y tablas -
Analysis 5.17

Comparison 5 Complications during primary hospitalisation, Outcome 17 Any retinopathy of prematurity (ROP).

Comparison 5 Complications during primary hospitalisation, Outcome 18 Severe ROP.
Figuras y tablas -
Analysis 5.18

Comparison 5 Complications during primary hospitalisation, Outcome 18 Severe ROP.

Comparison 5 Complications during primary hospitalisation, Outcome 19 Severe ROP in survivors.
Figuras y tablas -
Analysis 5.19

Comparison 5 Complications during primary hospitalisation, Outcome 19 Severe ROP in survivors.

Comparison 6 Long‐term follow‐up, Outcome 1 Bayley Mental Developmental Index (MDI) <‐2 SD.
Figuras y tablas -
Analysis 6.1

Comparison 6 Long‐term follow‐up, Outcome 1 Bayley Mental Developmental Index (MDI) <‐2 SD.

Comparison 6 Long‐term follow‐up, Outcome 2 Bayley MDI <‐2 SD in tested survivors.
Figuras y tablas -
Analysis 6.2

Comparison 6 Long‐term follow‐up, Outcome 2 Bayley MDI <‐2 SD in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD.
Figuras y tablas -
Analysis 6.3

Comparison 6 Long‐term follow‐up, Outcome 3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD.

Comparison 6 Long‐term follow‐up, Outcome 4 Bayley PDI <‐2 SD in tested survivors.
Figuras y tablas -
Analysis 6.4

Comparison 6 Long‐term follow‐up, Outcome 4 Bayley PDI <‐2 SD in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 5 Developmental delay (criteria not specified).
Figuras y tablas -
Analysis 6.5

Comparison 6 Long‐term follow‐up, Outcome 5 Developmental delay (criteria not specified).

Comparison 6 Long‐term follow‐up, Outcome 6 Developmental delay (criteria not specified) in tested survivors.
Figuras y tablas -
Analysis 6.6

Comparison 6 Long‐term follow‐up, Outcome 6 Developmental delay (criteria not specified) in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 7 Blindness.
Figuras y tablas -
Analysis 6.7

Comparison 6 Long‐term follow‐up, Outcome 7 Blindness.

Comparison 6 Long‐term follow‐up, Outcome 8 Blindness in survivors assessed.
Figuras y tablas -
Analysis 6.8

Comparison 6 Long‐term follow‐up, Outcome 8 Blindness in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 9 Deafness.
Figuras y tablas -
Analysis 6.9

Comparison 6 Long‐term follow‐up, Outcome 9 Deafness.

Comparison 6 Long‐term follow‐up, Outcome 10 Deafness in survivors assessed.
Figuras y tablas -
Analysis 6.10

Comparison 6 Long‐term follow‐up, Outcome 10 Deafness in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 11 Cerebral palsy.
Figuras y tablas -
Analysis 6.11

Comparison 6 Long‐term follow‐up, Outcome 11 Cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 12 Death before follow‐up in trials assessing cerebral palsy.
Figuras y tablas -
Analysis 6.12

Comparison 6 Long‐term follow‐up, Outcome 12 Death before follow‐up in trials assessing cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 13 Death or cerebral palsy.
Figuras y tablas -
Analysis 6.13

Comparison 6 Long‐term follow‐up, Outcome 13 Death or cerebral palsy.

Comparison 6 Long‐term follow‐up, Outcome 14 Cerebral palsy in survivors assessed.
Figuras y tablas -
Analysis 6.14

Comparison 6 Long‐term follow‐up, Outcome 14 Cerebral palsy in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 15 Major neurosensory disability (variable criteria ‐ see individual studies).
Figuras y tablas -
Analysis 6.15

Comparison 6 Long‐term follow‐up, Outcome 15 Major neurosensory disability (variable criteria ‐ see individual studies).

Comparison 6 Long‐term follow‐up, Outcome 16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria).
Figuras y tablas -
Analysis 6.16

Comparison 6 Long‐term follow‐up, Outcome 16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 17 Death or major neurosensory disability (variable criteria).
Figuras y tablas -
Analysis 6.17

Comparison 6 Long‐term follow‐up, Outcome 17 Death or major neurosensory disability (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 18 Major neurosensory disability in survivors examined (variable criteria).
Figuras y tablas -
Analysis 6.18

Comparison 6 Long‐term follow‐up, Outcome 18 Major neurosensory disability in survivors examined (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 19 Abnormal neurological exam (variable criteria ‐ see individual studies).
Figuras y tablas -
Analysis 6.19

Comparison 6 Long‐term follow‐up, Outcome 19 Abnormal neurological exam (variable criteria ‐ see individual studies).

Comparison 6 Long‐term follow‐up, Outcome 20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria).
Figuras y tablas -
Analysis 6.20

Comparison 6 Long‐term follow‐up, Outcome 20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 21 Death or abnormal neurological exam (variable criteria).
Figuras y tablas -
Analysis 6.21

Comparison 6 Long‐term follow‐up, Outcome 21 Death or abnormal neurological exam (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 22 Abnormal neurological exam in tested survivors (variable criteria).
Figuras y tablas -
Analysis 6.22

Comparison 6 Long‐term follow‐up, Outcome 22 Abnormal neurological exam in tested survivors (variable criteria).

Comparison 6 Long‐term follow‐up, Outcome 23 Intellectual impairment (IQ < 70).
Figuras y tablas -
Analysis 6.23

Comparison 6 Long‐term follow‐up, Outcome 23 Intellectual impairment (IQ < 70).

Comparison 6 Long‐term follow‐up, Outcome 24 Intellectual impairment (IQ < 70) in survivors assessed.
Figuras y tablas -
Analysis 6.24

Comparison 6 Long‐term follow‐up, Outcome 24 Intellectual impairment (IQ < 70) in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 25 "Major neurosensory impairment" ‐ blindness or deafness.
Figuras y tablas -
Analysis 6.25

Comparison 6 Long‐term follow‐up, Outcome 25 "Major neurosensory impairment" ‐ blindness or deafness.

Comparison 6 Long‐term follow‐up, Outcome 26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed.
Figuras y tablas -
Analysis 6.26

Comparison 6 Long‐term follow‐up, Outcome 26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 27 Behaviour abnormalities.
Figuras y tablas -
Analysis 6.27

Comparison 6 Long‐term follow‐up, Outcome 27 Behaviour abnormalities.

Comparison 6 Long‐term follow‐up, Outcome 28 Behaviour abnormalities in 3‐year‐old survivors assessed.
Figuras y tablas -
Analysis 6.28

Comparison 6 Long‐term follow‐up, Outcome 28 Behaviour abnormalities in 3‐year‐old survivors assessed.

Comparison 6 Long‐term follow‐up, Outcome 29 Abnormal EEG.
Figuras y tablas -
Analysis 6.29

Comparison 6 Long‐term follow‐up, Outcome 29 Abnormal EEG.

Comparison 6 Long‐term follow‐up, Outcome 30 Abnormal EEG in tested survivors.
Figuras y tablas -
Analysis 6.30

Comparison 6 Long‐term follow‐up, Outcome 30 Abnormal EEG in tested survivors.

Comparison 6 Long‐term follow‐up, Outcome 31 Rehospitalisation in infancy.
Figuras y tablas -
Analysis 6.31

Comparison 6 Long‐term follow‐up, Outcome 31 Rehospitalisation in infancy.

Comparison 6 Long‐term follow‐up, Outcome 32 Rehospitalisation in infancy in survivors.
Figuras y tablas -
Analysis 6.32

Comparison 6 Long‐term follow‐up, Outcome 32 Rehospitalisation in infancy in survivors.

Summary of findings for the main comparison. Early systemic postnatal corticosteroids compared with placebo or no treatment for preventing bronchopulmonary dysplasia in preterm infants

Early systemic postnatal corticosteroids compared with placebo or no treatment for preventing bronchopulmonary dysplasia in preterm infants

Patient or population: preventing bronchopulmonary dysplasia in preterm infants
Setting: neonatal intensive care units
Intervention: early systemic postnatal corticosteroids
Comparison: placebo or no treatment

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo or no treatment

Risk with early systemic postnatal corticosteroids

Mortality at 36 weeks

Study population

RR 1.01
(0.89 to 1.14)

3733
(20 RCTs)

⊕⊕⊕⊕
HIGH

211 per 1000

213 per 1000
(188 to 241)

Mortality at latest reported age

Study population

RR 0.95
(0.85 to 1.06)

4373
(31 RCTs)

⊕⊕⊕⊝
MODERATEa

232 per 1000

221 per 1000
(197 to 246)

BPD (36 weeks)

Study population

RR 0.79
(0.72 to 0.87)

3929
(24 RCTs)

⊕⊕⊕⊝
MODERATEb

322 per 1000

254 per 1000
(232 to 280)

Death or BPD at 36 weeks

Study population

RR 0.88
(0.83 to 0.93)

3960
(25 RCTs)

⊕⊕⊕⊝
MODERATEb

531 per 1000

467 per 1000
(441 to 494)

Gastrointestinal perforation

Study population

RR 1.72
(1.29 to 2.30)

3040
(16 RCTs)

⊕⊕⊕⊕
HIGH

43 per 1000

74 per 1000
(56 to 99)

Cerebral palsy

Study population

RR 1.42
(1.06 to 1.91)

1973
(13 RCTs)

⊕⊕⊕⊕
HIGH

74 per 1000

106 per 1000
(79 to 142)

Death or cerebral palsy

Study population

RR 1.03
(0.91 to 1.16)

1973
(13 RCTs)

⊕⊕⊕⊝
MODERATEc

335 per 1000

345 per 1000
(305 to 389)

*The risk in the intervention group (and its 95% confidence interval) is based on assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; OR: odds ratio; 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.

aDowngraded one level for serious study limitations owing to weak evidence for publication bias, particularly for studies of hydrocortisone.

bDowngraded one level for serious study limitations owing to weak evidence for publication bias, for both dexamethasone and hydrocortisone studies.

cDowngraded one level for serious study limitations owing to moderate heterogeneity, particularly for studies of dexamethasone.

Figuras y tablas -
Summary of findings for the main comparison. Early systemic postnatal corticosteroids compared with placebo or no treatment for preventing bronchopulmonary dysplasia in preterm infants
Comparison 1. Mortality

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Neonatal mortality (up to 28 days) Show forest plot

19

2950

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.88, 1.19]

1.1 Dexamethasone

16

2603

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.90, 1.24]

1.2 Hydrocortisone

3

347

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.50, 1.23]

2 Mortality at 36 weeks Show forest plot

20

3733

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.89, 1.14]

2.1 Dexamethasone

14

2487

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.94, 1.25]

2.2 Hydrocortisone

6

1246

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.65, 1.06]

3 Mortality to hospital discharge Show forest plot

30

4273

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.85, 1.07]

3.1 Dexamethasone

19

2840

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.90, 1.18]

3.2 Hydrocortisone

11

1433

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.65, 0.98]

4 Mortality at latest reported age Show forest plot

31

4373

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.85, 1.06]

4.1 Dexamethasone

20

2940

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.90, 1.16]

4.2 Hydrocortisone

11

1433

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.65, 0.99]

Figuras y tablas -
Comparison 1. Mortality
Comparison 2. Bronchopulmonary dysplasia (BPD)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 BPD (28 days of life) Show forest plot

17

2874

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.81, 0.93]

1.1 Dexamethasone

16

2621

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.79, 0.92]

1.2 Hydrocortisone

1

253

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.85, 1.18]

2 BPD (36 weeks' postmenstrual age) Show forest plot

24

3929

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.72, 0.87]

2.1 Dexamethasone

16

2584

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.62, 0.81]

2.2 Hydrocortisone

8

1345

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.80, 1.05]

3 BPD at 36 weeks' postmenstrual age in survivors Show forest plot

21

2970

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.74, 0.88]

3.1 Dexamethasone

14

1917

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.64, 0.83]

3.2 Hydrocortisone

7

1053

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.80, 1.03]

4 Late rescue with corticosteroids Show forest plot

14

2483

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.68, 0.82]

4.1 Dexamethasone

10

1974

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.65, 0.80]

4.2 Hydrocortisone

4

509

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.73, 1.40]

5 Survivors who had late rescue with corticosteroids Show forest plot

7

895

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.67, 0.89]

5.1 Dexamethasone

6

853

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.68, 0.91]

5.2 Hydrocortisone

1

42

Risk Ratio (M‐H, Fixed, 95% CI)

0.48 [0.24, 0.98]

6 Survivors discharged home on oxygen Show forest plot

6

691

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.51, 1.03]

6.1 Dexamethasone

3

406

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.48, 1.26]

6.2 Hydrocortisone

3

285

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.40, 1.11]

Figuras y tablas -
Comparison 2. Bronchopulmonary dysplasia (BPD)
Comparison 3. Death or bronchopulmonary dysplasia (BPD)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death or BPD at 28 days of life Show forest plot

15

2546

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.88, 0.96]

1.1 Dexamethasone

14

2293

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.86, 0.96]

1.2 Hydrocortisone

1

253

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.90, 1.12]

2 Death or BPD at 36 weeks' postmenstrual age Show forest plot

25

3960

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.83, 0.93]

2.1 Dexamethasone

16

2581

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.80, 0.94]

2.2 Hydrocortisone

9

1379

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.82, 0.99]

Figuras y tablas -
Comparison 3. Death or bronchopulmonary dysplasia (BPD)
Comparison 4. Failure to extubate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Failure to extubate by third day Show forest plot

4

887

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.75, 0.95]

1.1 Dexamethasone

3

381

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.62, 0.86]

1.2 Hydrocortisone

1

506

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.82, 1.14]

2 Failure to extubate by seventh day Show forest plot

8

1448

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.68, 0.85]

2.1 Dexamethasone

6

703

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.61, 0.84]

2.2 Hydrocortisone

2

745

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.69, 0.94]

3 Failure to extubate by 14th day Show forest plot

4

443

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.62, 0.97]

4 Failure to extubate by 28th day Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.72, 0.98]

Figuras y tablas -
Comparison 4. Failure to extubate
Comparison 5. Complications during primary hospitalisation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Infection Show forest plot

25

4101

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.96, 1.15]

1.1 Dexamethasone

18

2821

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.91, 1.15]

1.2 Hydrocortisone

7

1280

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.94, 1.25]

2 Hyperglycaemia Show forest plot

13

2167

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [1.20, 1.47]

2.1 Dexamethasone

12

2117

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [1.21, 1.49]

2.2 Hydrocortisone

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.50, 1.67]

3 Hypertension Show forest plot

11

1993

Risk Ratio (M‐H, Fixed, 95% CI)

1.85 [1.54, 2.22]

3.1 Dexamethasone

10

1943

Risk Ratio (M‐H, Fixed, 95% CI)

1.84 [1.53, 2.21]

3.2 Hydrocortisone

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.33, 26.92]

4 Hypertrophic cardiomyopathy Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

4.33 [1.40, 13.37]

5 Growth failure Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

6.67 [2.27, 19.62]

6 Pulmonary air leak Show forest plot

16

3225

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.74, 1.13]

6.1 Dexamethasone

12

2041

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.66, 1.08]

6.2 Hydrocortisone

4

1184

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.75, 1.65]

7 Patent ductus arteriosus (PDA) Show forest plot

24

4013

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.72, 0.85]

7.1 Dexamethasone

17

2706

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.69, 0.84]

7.2 Hydrocortisone

7

1307

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.71, 0.95]

8 Severe IVH Show forest plot

26

4103

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.83, 1.11]

8.1 Dexamethasone

17

2736

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.81, 1.14]

8.2 Hydrocortisone

9

1367

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.74, 1.23]

9 Severe intraventricular haemorrhage (IVH) in infants examined Show forest plot

7

1909

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.11]

10 Periventricular leukomalacia (PVL) Show forest plot

15

2807

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.78, 1.46]

10.1 Dexamethasone

8

1514

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.84, 1.81]

10.2 Hydrocortisone

7

1293

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.46, 1.40]

11 PVL in infants with cranial ultrasound scans Show forest plot

7

1841

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.79, 1.60]

12 PVL in survivors seen at follow‐up Show forest plot

2

183

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.60, 2.48]

13 Necrotising enterocolitis (NEC) Show forest plot

25

4050

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.11]

13.1 Dexamethasone

15

2661

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.69, 1.13]

13.2 Hydrocortisone

10

1389

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.66, 1.37]

14 Gastrointestinal bleeding Show forest plot

12

1816

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.35, 2.55]

14.1 Dexamethasone

10

1725

Risk Ratio (M‐H, Fixed, 95% CI)

1.87 [1.35, 2.58]

14.2 Hydrocortisone

2

91

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.27, 8.74]

15 Gastrointestinal perforation Show forest plot

16

3040

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.02, 0.05]

15.1 Dexamethasone

9

1936

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.01, 0.05]

15.2 Hydrocortisone

7

1104

Risk Difference (M‐H, Fixed, 95% CI)

0.03 [0.00, 0.06]

16 Pulmonary haemorrhage Show forest plot

10

1820

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.87, 1.54]

16.1 Dexamethasone

7

686

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.65, 1.45]

16.2 Hydrocortisone

3

1134

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.92, 2.03]

17 Any retinopathy of prematurity (ROP) Show forest plot

9

1345

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.80, 0.97]

17.1 Dexamethasone

8

1042

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.72, 0.99]

17.2 Hydrocortisone

1

303

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.84, 1.04]

18 Severe ROP Show forest plot

14

2577

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.66, 0.98]

18.1 Dexamethasone

8

1507

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.60, 0.99]

18.2 Hydrocortisone

6

1070

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.63, 1.21]

19 Severe ROP in survivors Show forest plot

12

1575

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.64, 0.94]

19.1 Dexamethasone

10

1238

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.59, 0.95]

19.2 Hydrocortisone

2

337

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.60, 1.17]

Figuras y tablas -
Comparison 5. Complications during primary hospitalisation
Comparison 6. Long‐term follow‐up

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Bayley Mental Developmental Index (MDI) <‐2 SD Show forest plot

3

842

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.78, 1.29]

2 Bayley MDI <‐2 SD in tested survivors Show forest plot

3

528

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.79, 1.25]

3 Bayley Psychomotor Developmental Index (PDI) <‐2 SD Show forest plot

3

842

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.85, 1.60]

4 Bayley PDI <‐2 SD in tested survivors Show forest plot

3

528

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.87, 1.57]

5 Developmental delay (criteria not specified) Show forest plot

1

248

Risk Ratio (M‐H, Fixed, 95% CI)

1.68 [1.08, 2.61]

6 Developmental delay (criteria not specified) in tested survivors Show forest plot

1

159

Risk Ratio (M‐H, Fixed, 95% CI)

1.94 [1.30, 2.88]

7 Blindness Show forest plot

8

939

Risk Ratio (M‐H, Fixed, 95% CI)

2.01 [0.74, 5.50]

8 Blindness in survivors assessed Show forest plot

8

585

Risk Ratio (M‐H, Fixed, 95% CI)

2.16 [0.80, 5.86]

9 Deafness Show forest plot

8

721

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.39, 3.37]

10 Deafness in survivors assessed Show forest plot

8

476

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.40, 3.29]

11 Cerebral palsy Show forest plot

13

1973

Risk Ratio (IV, Fixed, 95% CI)

1.42 [1.06, 1.91]

11.1 Dexamethasone

7

921

Risk Ratio (IV, Fixed, 95% CI)

1.75 [1.20, 2.55]

11.2 Hydrocortisone

6

1052

Risk Ratio (IV, Fixed, 95% CI)

1.05 [0.66, 1.66]

12 Death before follow‐up in trials assessing cerebral palsy Show forest plot

13

1973

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.78, 1.05]

12.1 Dexamethasone

7

921

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.81, 1.21]

12.2 Hydrocortisone

6

1052

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.64, 1.02]

13 Death or cerebral palsy Show forest plot

13

1973

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.91, 1.16]

13.1 Dexamethasone

7

921

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [1.00, 1.37]

13.2 Hydrocortisone

6

1052

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.71, 1.05]

14 Cerebral palsy in survivors assessed Show forest plot

13

1328

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [1.11, 1.90]

14.1 Dexamethasone

7

586

Risk Ratio (M‐H, Fixed, 95% CI)

1.82 [1.29, 2.57]

14.2 Hydrocortisone

6

742

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.65, 1.58]

15 Major neurosensory disability (variable criteria ‐ see individual studies) Show forest plot

7

1703

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.89, 1.33]

15.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.03, 1.83]

15.2 Hydrocortisone

3

931

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.64, 1.14]

16 Death before follow‐up in trials assessing major neurosensory disability (variable criteria) Show forest plot

6

1182

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.81, 1.17]

16.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.82, 1.25]

16.2 Hydrocortisone

2

410

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.58, 1.28]

17 Death or major neurosensory disability (variable criteria) Show forest plot

7

1703

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.87, 1.08]

17.1 Dexamethasone

4

772

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.99, 1.30]

17.2 Hydrocortisone

3

931

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.69, 0.97]

18 Major neurosensory disability in survivors examined (variable criteria) Show forest plot

8

1178

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.89, 1.28]

18.1 Dexamethasone

4

469

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [1.05, 1.77]

18.2 Hydrocortisone

4

709

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.65, 1.10]

19 Abnormal neurological exam (variable criteria ‐ see individual studies) Show forest plot

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

1.81 [1.33, 2.47]

20 Death before follow‐up in trials assessing abnormal neurological exam (variable criteria) Show forest plot

6

1350

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.75, 1.07]

20.1 Dexamethasone

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.79, 1.21]

20.2 Hydrocortisone

1

521

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.54, 1.04]

21 Death or abnormal neurological exam (variable criteria) Show forest plot

5

829

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [1.06, 1.42]

22 Abnormal neurological exam in tested survivors (variable criteria) Show forest plot

5

508

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [1.41, 2.52]

23 Intellectual impairment (IQ < 70) Show forest plot

2

90

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [0.57, 3.31]

24 Intellectual impairment (IQ < 70) in survivors assessed Show forest plot

2

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.47, 2.65]

25 "Major neurosensory impairment" ‐ blindness or deafness Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.25]

26 "Major neurosensory impairment" ‐ blindness or deafness ‐ in survivors assessed Show forest plot

1

45

Risk Ratio (M‐H, Fixed, 95% CI)

0.57 [0.16, 2.12]

27 Behaviour abnormalities Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.25]

28 Behaviour abnormalities in 3‐year‐old survivors assessed Show forest plot

1

46

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.16, 2.22]

29 Abnormal EEG Show forest plot

2

306

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.66, 2.33]

30 Abnormal EEG in tested survivors Show forest plot

2

146

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.61, 2.08]

31 Rehospitalisation in infancy Show forest plot

3

672

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.68, 1.08]

32 Rehospitalisation in infancy in survivors Show forest plot

3

430

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.71, 1.07]

Figuras y tablas -
Comparison 6. Long‐term follow‐up