Kortikosteroid antenatal bagi mempercepat proses kematangan paru‐paru janin dalam kalangan wanita yang berisiko untuk bersalin pramatang
Referencias
References to studies included in this review
References to studies excluded from this review
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Instituto Materno‐Infantil de Pernambuco, Recife, state of Pernambuco, Brazil | |
| Interventions | 12 mg betamethasone IM, repeated after 24 h and weekly thereafter if delivery had not occurred. | |
| Outcomes | Maternal outcomes (death, chorioamnionitis, maternal infection, fever after trial entry requiring antibiotics, intrapartum fever requiring antibiotics, postnatal fever, admission to ICU, glucose intolerance, hypertension), fetal/neonatal outcomes (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, Apgar score < 7, interval between trial entry and delivery, small‐for‐gestational age, admission to NICU, need for mechanical ventilation/CPAP, duration of oxygen supplementation, surfactant use, systemic infection in the first 48 h of life, proven infection while in the NICU, necrotising enterocolitis), childhood outcomes (death, developmental delay, cerebral palsy) and health service outcomes reported (length of antenatal hospitalisation for women, length of postnatal hospitalisation for women, length of neonatal hospitalisation) | |
| Notes | Further information obtained from the study authors, including substantial unpublished data | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Computer‐generated randomisation sequence." |
| Allocation concealment (selection bias) | Low risk | "Randomisation code kept by the chief pharmacist." |
| Blinding of participants and personnel (performance bias) | Low risk | Participants and investigators were blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Blinding of outcome assessors was not described, but it is likely as the authors state, "the data analysis was carried out without knowledge of which of the treatments corresponded to corticosteroid and which to placebo". The code was fully broken only after the analysis was completed. |
| Incomplete outcome data (attrition bias) | Low risk | 2 women (1%) in the placebo group voluntarily dropped out after randomisation. |
| Selective reporting (reporting bias) | Low risk | Study protocol was not available, but study appears to report on all pre‐specified outcomes |
| Other bias | Low risk | The groups were comparable at baseline. The study appears free of other sources of bias. |
| Study characteristics | ||
| Methods | Type of study: open label RCT Stratification: none stated | |
| Participants | Location: Chonburi Hospital, Thailand Gestational age range: 34 weeks + 0 d‐36 weeks + 6 d | |
| Interventions | The treatment group received 6 mg dexamethasone IM, up to 4 doses 12 h apart. The control group received no treatment. | |
| Outcomes | Maternal outcomes (chorioamnionitis, side effects of therapy in women) Fetal/neonatal outcomes (RDS, IVH, birthweight, necrotising enterocolitis, systemic infection in the first 48 h of life, need for mechanical ventilation/CPAP, Apgar score < 7, admission to NICU) | |
| Notes | Labour augmentation performed if needed even if women had not received full course of steroids. 6 (6%) women in the intervention group received a full course of steroids; most women (75/96 (78%)) in the intervention arm received just 1 dose of dexamethasone. Data for 'maternal local or systemic adverse reactions to treatment' have been included in the review under our outcome of maternal side effects. Data from the trial are available for the following outcomes: low birthweight (not defined); hypoglycaemia in infant; need for respiratory support in infant (6/96 treatment and 14/98 control; (these data are in addition to the need for 'positive pressure ventilation' included in the review outcome 'need for mechanical ventilation'); and maternal length of stay (not separated into intrapartum and postpartum) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not reported. Method reported as block randomisation only |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) | High risk | Open label, participants would have been aware of allocation. Delivery nurse not blinded but all other hospital staff delivering care were blind |
| Blinding of outcome assessment (detection bias) | Unclear risk | The data were retrieved from chart review and hospital staff were blinded apart from delivery room nurses. |
| Incomplete outcome data (attrition bias) | Low risk | 5 women in the dexamethasone delivered after 1 week and were included in ITT analysis |
| Selective reporting (reporting bias) | Low risk | Relevant outcome data reported |
| Other bias | Low risk | The groups were comparable at baseline. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Dept of Obstetrics and Gynecology, Hospital of Meram, Faculty of Medicine, Selcuk University, Konya, Turkey Gestational age range: 34 + 0‐36 + 0 weeks | |
| Interventions | The treatment group received a single dose of 12 mg betamethasone IM. The control group received no treatment. Women who delivered at least 24 h after betamethasone administration were included in the study. | |
| Outcomes | Apgar score at 1 and 5 minutes, need for resuscitation, development of RDS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Generated by a computer" |
| Allocation concealment (selection bias) | Unclear risk | "Sequential sealed envelopes" not stated if opaque or not |
| Blinding of participants and personnel (performance bias) | High risk | Due to comparison group receiving no treatment and treatment group receiving corticosteroids, blinding of participants and personnel would not have been possible. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors is not described. |
| Incomplete outcome data (attrition bias) | Unclear risk | 30 infants with fetal distress, meconium‐stained liquor and who delivered within less than 24 h were excluded from the study (14 in control group, 16 in steroid group). Intention‐to‐treat analysis was used |
| Selective reporting (reporting bias) | High risk | Maternal complications were not pre‐specified but were reported |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Department of Gynecology and Obstetrics at the University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA | |
| Interventions | 12 mg betamethasone IM repeated after 24 h if delivery had not occurred If there was evidence of progressive cervical dilatation an alcohol infusion was given in order to attempt to delay delivery for at least 48 h. In women with PROM delivery was induced if serial white blood cell counts or temperatures became elevated regardless of time elapsed since drug administration. | |
| Outcomes | Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, need for mechanical ventilation/CPAP) | |
| Notes | This study included a third arm (125 mg methylprednisolone IM repeated after 24 h if delivery had not occurred). The data for the review report the betamethasone and control arms only. Overall data were available for 150 living infants, of whom 128 were preterm. Further information was requested from the study authors but there was no reply. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Computer generated randomisation sequence." |
| Allocation concealment (selection bias) | Low risk | "Consecutively numbered boxes containing randomly selected study drug or placebo." |
| Blinding of participants and personnel (performance bias) | Low risk | Clinicians were never aware of the contents of the coded box. Placeob was saline so it is likely that participants were blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Unclear risk | 14 (10%) women delivered elsewhere and were lost to follow‐up. 6 (4%) women were excluded from analyses as they failed to complete the protocol (1 in the betamethasone group, 2 in the methylprednisolone group, and 3 in the control group). |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes. |
| Other bias | Unclear risk | Insufficient information to assess if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Hospital Clinic, University of Barcelona, Spain | |
| Interventions | Type and dose of corticosteroid used in the treatment group is not stated | |
| Outcomes | Fetal/neonatal outcome reported (RDS) | |
| Notes | Study only available as an abstract. Further information was requested from the study authors but there was no reply | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel not stated, although unlikely as placebo was not used |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment was not stated |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up |
| Selective reporting (reporting bias) | Unclear risk | Study only available as an abstract |
| Other bias | Unclear risk | Study was only available as an abstract. Further information was requested from the study authors, but there was no reply |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: University of South Florida Medical School, Tampa, Florida, USA | |
| Interventions | 12 mg betamethasone IM repeated after 24 h and weekly thereafter until delivery or 34 weeks. | |
| Outcomes | Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (RDS, birthweight, days of mechanical ventilation/CPAP) and health service outcomes reported (days in NICU, neonatal days in hospital, neonatal hospital cost). However due to lack of SD data only chorioamnionitis and RDS data were included in the review. | |
| Notes | This study included a third arm (12 mg betamethasone IM 24‐hourly for 2 doses and 400 mcg methylprednisolone IV 8‐hourly for 6 doses, repeated weekly until delivery or 34 weeks. The data for the review report the betamethasone and control arms only. Further information was requested from the study authors but there was no reply. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel not stated, although unlikely as placebo was not used |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not stated |
| Incomplete outcome data (attrition bias) | Low risk | 2 (8%) infants with documented pulmonary maturity and 5 (17%) women with subsequent sealed membranes were not analysed |
| Selective reporting (reporting bias) | Unclear risk | SD data not stated so a number of outcomes are not able to be included in the review |
| Other bias | Unclear risk | Only available as an abstract. Full paper not published |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 5 university hospitals in the USA | |
| Interventions | 4 doses of 5 mg dexamethasone phosphate IM 12 h apart | |
| Outcomes | Maternal outcomes (postnatal fever), fetal/neonatal outcomes (fetal death, neonatal death, RDS, birthweight, interval between trial entry and delivery, systemic infection in the first 48 h of life, proven infection while in the NICU, necrotising enterocolitis), childhood outcomes (death, lung function, developmental delay, intellectual impairment, cerebral palsy) and health service outcomes were reported (length of neonatal hospitalisation) | |
| Notes | Further information was requested from the authors but there was no reply | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | High risk | Sealed envelope containing the identity of the contents of was attached to each vial "to be opened in emergency only in case of an emergency". The manuscripts do not state how often these were opened. |
| Blinding of participants and personnel (performance bias) | Low risk | "Both placebo and steroid were dispensed as 10 ml clear, colourless solutions which differed only in that one contained the steroid". It is likely that participants were blinded. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Unclear risk | 2 (0.27%) infants in the control arm were lost to RDS follow‐up as neonates. At age 3, 240 (37%) children were lost to follow‐up (124 in the treatment arm and 116 in the control arm), or had died (47 in the treatment arm and 46 in the control arm). |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 6 hospitals in South Africa | |
| Interventions | 2 doses of 12 mg dexamethasone IM 24 h apart All women also received ampicillin, metronidazole and hexoprenaline if contractions present in < 24 h | |
| Outcomes | Maternal outcomes (maternal death, chorioamnionitis, endometritis, postnatal fever), fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, IVH, birthweight, need for mechanical ventilation/CPAP, systemic infection in the first 48 h of life, necrotising enterocolitis) | |
| Notes | Study authors supplied additional data | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Central allocation. Sequentially‐numbered drug boxes were used |
| Blinding of participants and personnel (performance bias) | Low risk | Blinding of participants likely as identical looking placebo was used. Blinding of study personnel was not described, other than "double blind". |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Low risk | 7 (3%) women and infants were excluded from analysis (3 women did not have PROM, 2 women were < 26 weeks at randomisation, 1 woman received off‐protocol corticosteroid, a neonatal bed was not available in 1 case) |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Study was discontinued before target sample size was reached due to increasing body of evidence of the use of corticosteroids in women with PPROM being advantageous to the infants, and it was felt unnecessary to conduct further trials of antenatal corticosteroids in women with PPROM |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 6 teaching hospitals in Toronto, Canada | |
| Interventions | 4 doses of 3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate IM 12 h apart | |
| Outcomes | Fetal/neonatal outcomes were reported (fetal death, neonatal death, RDS, IVH, birthweight, days of mechanical ventilation) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Low risk | Coded drug boxes were provided. Randomisation code was kept on file at the Pharmacy Department of Toronto General Hospital. |
| Blinding of participants and personnel (performance bias) | Low risk | It is likely that participants were blinded as both placebo and corticosteroid solutions were identical. Blinding of study personnel was not described other than to state "double blind". |
| Blinding of outcome assessment (detection bias) | Low risk | Blinding of outcome assessors was not described, but is likely as the authors state "The key to the code was not broken until the whole study was completed". |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: CHU Farhat Hached, Sousse, Tunisia | |
| Interventions | Abstract and full report state slightly different protocols for the intervention arm. The abstract stated that 24 mg betamethasone was given as two 12 mg IM doses at 24 h apart. The full text states that this regimen was repeated weekly. Women had two doses of 12 mg given 24 h apart, and this regimen was repeated weekly. | |
| Outcomes | Maternal outcomes (chorioamnionitis, postnatal fever) and fetal/neonatal outcomes reported (neonatal death, RDS, IVH) | |
| Notes | Article in French, abstract in English. Article translated by review authors (La Tunisie Medicale, 2002, Vol 80; No. 5: 260‐265). Further information was requested from the study authors but there was no reply | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment was not stated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding is unlikely as placebo was not used |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described |
| Incomplete outcome data (attrition bias) | Unclear risk | Number of post‐randomisation exclusions not stated |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 11 hospitals in the UK | |
| Interventions | 6 doses of 4 mg betamethasone phosphate IM 8 h apart All women with spontaneous labour received IV salbutamol | |
| Outcomes | Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, IVH, birthweight, systemic infection in the first 48 h of life) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | Low risk | It is likely that participants were blinded as placebo was used. Blinding of study personnel was not described other than "double‐blind". |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not stated. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up reported |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Long Beach Memorial Women's Hospital, California, USA | |
| Interventions | 2 doses of 6 mg betamethasone acetate and 6 mg betamethasone phosphate IM 24 h apart, repeated weekly if still < 28 weeks and thought likely to deliver within the next week | |
| Outcomes | Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, Apgar < 7, need for mechanical ventilation/CPAP, duration of mechanical ventilation/CPAP, proven neonatal infection while in NICU) | |
| Notes | It is not stated how many women received corticosteroids off protocol. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random‐number table generated randomisation sequence by pharmacy |
| Allocation concealment (selection bias) | Unclear risk | The pharmacy provided consecutive sealed envelopes, not stated if envelopes were opaque |
| Blinding of participants and personnel (performance bias) | Low risk | It is likely that participants were blinded as placebo was used. Blinding of study personnel was not described other than "double‐blind" |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Low risk | 5 (7%) women delivered elsewhere and were lost to follow‐up (4 in treatment arm and 1 in control arm). |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | It is not stated how many women received corticosteroids off protocol. |
| Study characteristics | ||
| Methods | Type of study: RCT (abstract) Stratification: not described | |
| Participants | Location: Temple University Hospital, Philadelphia, Pennsylvania, USA | |
| Interventions | Treatment group received an IM injection of betamethasone. The control group received an IM injection of saline as placebo. | |
| Outcomes | Neonatal mortality, RDS | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not stated other than "randomized" |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) | Low risk | Likely that participants were blinded and possible that study personnel were blinded due to the use of placebo |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessor not stated |
| Incomplete outcome data (attrition bias) | Unclear risk | Not stated |
| Selective reporting (reporting bias) | High risk | RDS is the only outcome reported. |
| Other bias | Unclear risk | Only available as an abstract ‐ does not appear to have been published |
| Study characteristics | ||
| Methods | Type of study: double‐blind, RCT Stratification: yes, according to clinical site and gestational age (34‐35 weeks and 36 weeks) | |
| Participants | Location: 17 university‐based clinics in the USA. All centres affiliated with the Maternal–Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. | |
| Interventions | Treatment group: (n = 1429 randomised) 2 IM injections of 12 mg betamethasone (equal parts betamethasone sodium phosphate and betamethasone acetate) administered 24 h apart Control group received matching placebo "For those enrolled because of an indication for preterm delivery, labor inductions were expected to start by 36 weeks 5 d, and cesarean deliveries were to be scheduled by 36 weeks 6 days and not before 24 hours after randomization." Control: (n = 1402 randomised) placebo IM injections as above Follow up: to 28 d for oxygen dependency outcome | |
| Outcomes | Maternal outcome (maternal death, chorioamnionitis, side effects of therapy in women), fetal/neonatal outcomes (perinatal death, fetal death, neonatal death, RDS, IVH, birthweight, necrotising enterocolitis, proven infection while in NICU, need for mechanical ventilation/CPAP, surfactant use, air leak syndrome, Apgar score < 7, small for gestation age, admission to NICU) We asked study authors to clarify the mechanical ventilation/CPAP data presented in Table 2 of the publication; we are unsure if outcome categories are exclusive or not. We have not included data from this trial in the meta‐analysis for 1.25 due to these concerns; data will be included at the next update if confirmed by study authors Data from trial is available for following non‐review outcomes: maternal serious adverse events, infant serious adverse events, hypoglycaemia in infant. Length of stay (maternal and infant) reported as median with IQR only. Randomisation to delivery interval reported as median with IQR only | |
| Notes | Supplementary appendix published online with data tables and additional information on trial methods relevant to risk of bias. Contact author confirmed no maternal deaths and blinding of researchers abstracting data from maternal and neonatal charts (24.2.2016 by email) ClinicalTrials.gov number, NCT01222247. Ruptured membranes occurred in 22.1% intervention and 21.7% controls
"A total of 860 of 1429 women (60.2%) in the betamethasone group and 826 of 1402 (58.9%) in the placebo group received the prespecified two doses of study medication. Of the 1145 women who did not receive a second dose, 1083 (94.6%) delivered before 24 hours; 6 women did not receive any of the assigned study medication. (In the placebo group, 3 women who consented to participate in the trial subsequently declined the injection, 1 woman delivered after randomization but before the first dose, and 1 received open label betamethasone. In the betamethasone group, 1 woman was in active labor with complete cervical dilation at the time of randomization.)" | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Independent data‐coordinating centre with the use of the simple urn method, with stratification according to clinical site and gestational age category (34 to 35 weeks vs. 36 weeks)" |
| Allocation concealment (selection bias) | Low risk | Remote centre performed randomisation and packaged intervention and placebo |
| Blinding of participants and personnel (performance bias) | Low risk | Identical treatment and placebo packs prepared remotely. Women and staff blinded |
| Blinding of outcome assessment (detection bias) | Low risk | Trained research staff extracted data from maternal and neonatal staff; authors confirmed by email that these researchers were blinded. Charts of babies admitted to special care were reviewed by blinded staff for respiratory outcomes |
| Incomplete outcome data (attrition bias) | Low risk | Two women in each group lost to follow‐up. Data available for 2827 neonates |
| Selective reporting (reporting bias) | Low risk | Supplementary outcome data published online with paper |
| Other bias | Low risk | Few baseline imbalances apart from mean maternal age (28.6 vs. 27.8 years) and Hispanic ethnic background (28.3 vs. 32%) |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 5 hospitals in Finland | |
| Interventions | 4 doses of 6 mg dexamethasone sodium phosphate IM 12 h apart | |
| Outcomes | Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, chronic lung disease, IVH, birthweight, surfactant use, necrotising enterocolitis, small‐for‐gestational age) and childhood outcomes reported (death, neurodevelopmental delay) | |
| Notes | Efficacy analysis restricted to 91 infants in treatment arm and 88 infants in control arm. 3 infants excluded for protocol violations (1 mother with twins in placebo arm was given corticosteroid, 1 infant in the treatment arm developed RDS but was not given surfactant as it was not available) and 6 infants were excluded because of congenital malformations (2 treatment, 4 placebo) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated. "Randomisation in each participating hospital was performed in blocks of 10" |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | Low risk | "The investigators and those who provided care were unaware of the treatment allocation". It is likely that participants were blinded as "ampoules containing betamethasone and placebo were identical". |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Low risk | 10 (11%) children in the follow‐up study at age 2 (2 in the treatment arm and 8 in the control arm). 1 female placebo‐treated infant born at 27 weeks' gestation died 3 months after the expected date of delivery, 4 infants were lost due to parental refusal, 2 were living overseas, and 3 were in other regions of the country |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Efficacy analysis restricted to 91 infants in treatment arm and 88 infants in control arm. 3 infants excluded for protocol violations (1 mother with twins in placebo arm was given corticosteroid, 1 infant in the treatment arm developed RDS but was not given surfactant as it was not available) and 6 infants were excluded because of congenital malformations (2 treatment, 4 placebo) |
| Study characteristics | ||
| Methods | Type of study: double‐blind RCT Stratification: none stated | |
| Participants | Location: Obstetric emergency department of Vali‐e‐Asr,Hospital, Tehran, Iran Timeframe: June 2006 to July 2010 Eligibility criteria: patients at risk of preterm labor as determined by routine ultrasound examination in the first trimester Gestational age range: 34‐37 weeks "Women with systemic diseases, maternal hypertension before or during pregnancy, uterine tenderness, chorioamnionitis signs, symptomatic vaginal infection, rupture of membranes, current use of antibiotics, induced pregnancy, and history of smoking were excluded." | |
| Interventions | The treatment group received 2 doses of 12 mg betamethasone IM. The control group received placebo of saline as per regimen above. | |
| Outcomes | No outcomes available for the review | |
| Notes | Data are provided on endocervical cytokine levels in women who delivered within and after 1 week but no outcome data available for the review are presented | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation sequence in blocks of 4 |
| Allocation concealment (selection bias) | Unclear risk | Only 1 person (research assistant) had access to the randomisation list. It is unclear whether this person was part of the team performing the study |
| Blinding of participants and personnel (performance bias) | Low risk | Placebo‐controlled trial ‐ saline was used as the placebo |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described |
| Incomplete outcome data (attrition bias) | High risk | Analysis was not by intention‐to‐treat. 5 participants in the intervention arm were excluded for named reasons and their data were not included |
| Selective reporting (reporting bias) | Low risk | All intended outcomes, i.e. cytokine measurements, were reported |
| Other bias | High risk | Data were analysed for 35 women in the intervention arm versus 40 in the control arm because 2 delivered before cytokine sampling after the second dose of betamethasone, 1 opted out of the study and 2 developed high blood pressure |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Louisiana State University Medical Center, Shreveport, Louisiana, USA | |
| Interventions | The treatment group received 12 mg IM betamethasone repeated at 24 h and weekly if the women had not delivered. | |
| Outcomes | Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes (neonatal death, RDS, IVH, birthweight, Apgar < 7, interval between trial entry and delivery, admission to NICU, surfactant use, proven neonatal infection while in NICU, necrotising enterocolitis) and health service outcome reported (length of neonatal hospitalisation) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Clinical research nurse uninvolved in clinical care generated randomisation sequence by using random‐number table, with a random permuted block size of 10 |
| Allocation concealment (selection bias) | Low risk | Sequentially‐numbered sealed opaque envelopes were used |
| Blinding of participants and personnel (performance bias) | High risk | Comparison was "no treatment" so blinding not possible |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described |
| Incomplete outcome data (attrition bias) | Low risk | 2 (2%) women left hospital against medical advice after randomisation and were lost to follow‐up (1 women in each arm) |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist |
| Study characteristics | ||
| Methods | Type of study: RCT Method of treatment allocation: random‐number table generated randomisation sequence by chief pharmacist. Pharmacy provided coded drug ampoules containing treatment or placebo Stratification: no Placebo: yes, of identical appearance Sample‐size calculation: no Intention‐to‐treat analyses: yes Losses to follow‐up: yes, 54 (18%) children in the follow‐up study at ages 4‐6 years (31 in the treatment arm and 23 in the control arm) and 412 (44%) adults in the follow‐up study at age 30 years (219 in the treatment arm and 193 in the control arm) Funding: Health Research Council of New Zealand, Auckland, New Zealand; Auckland Medical Research Foundation, Auckland, New Zealand; and New Zealand Lottery Grants Board, Wellington, New Zealand | |
| Participants | Location: National Women's Hospital, Auckland, New Zealand Timeframe: December 1969 and February 1974 Eligibility criteria: women with threatened or planned preterm delivery Gestational age range: 24‐36 weeks Exclusion criteria: imminent delivery, contraindication to corticosteroids Total recruited: 1142 women and 1218 infants; 560 women and 601 infants in the treatment arm and 582 women and 617 infants in the control arm | |
| Interventions | The treatment group 2 doses of 6 mg betamethasone phosphate and 6 mg betamethasone acetate IM 24 h apart. After the first 717 women had enrolled, the treatment intervention was doubled to 2 doses of 12 mg betamethasone phosphate and 12 mg betamethasone acetate IM 24 h apart. | |
| Outcomes | Maternal outcome (chorioamnionitis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, cerebroventricular haemorrhage, mean birthweight, Apgar score < 7, mean interval between trial entry and delivery, proven infection while in NICU), childhood outcomes (death, mean weight, mean height, mean head circumference, mean lung function, mean blood pressure, intellectual impairment, cerebral palsy) and adulthood outcomes were reported (death, mean weight, mean height, mean head circumference, mean skin fold thickness, mean blood pressure, glucose impairment, HPA axis function, mean cholesterol, educational achievement, visual impairment, hearing impairment, intellectual impairment) | |
| Notes | Review includes new intention‐to‐treat analysis of the complete study and additional data due to the study authors providing individual participant study records | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random‐number table generated randomisation sequence by chief pharmacist |
| Allocation concealment (selection bias) | Low risk | Pharmacy provided coded drug ampoules containing treatment or placebo |
| Blinding of participants and personnel (performance bias) | Low risk | Blinding of study personnel was not described. It is likely that participants were blinded as placebo was of identical appearance to the corticosteroid. |
| Blinding of outcome assessment (detection bias) | Low risk | For the diagnosis of RDS, clinical records and chest radiographs were assessed separately and independently, by 1 of the study authors, and by a radiologist. |
| Incomplete outcome data (attrition bias) | Unclear risk | Incomplete outcome data for 54 (18%) children in the follow‐up study at ages 4‐6 (31 in the treatment arm and 23 in the control arm) and 412 (44%) adults in the follow‐up study at age 30 (219 in the treatment arm and 193 in the control arm) |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT Stratification: not stated | |
| Participants | Location: Department of Obstetrics and Gynecology, Faculty of Medicine, National Univeristy of Colombia | |
| Interventions | The treatment group received 2 doses of 12 mg betamethasone IM, 12 h apart. The control group received no treatment. | |
| Outcomes | Neonatal mortality, RDS, Apgar score < 7 at 5 min, systemic infection in first 48 h | |
| Notes | Original article in Spanish, translated into English | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not stated other than "patients were classified randomly into groups" |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) | High risk | Comparison is "no treatment" so blinding not possible |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up reported |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: double‐blind RCT Stratification: not stated Double‐blind, randomised controlled trial in Kurdistan University of Medical Sciences, Sanandaj, Iran | |
| Participants | Location: Kurdistan University of Medical Sciences, Sanandaj, Iran | |
| Interventions | The treatment group received 2 doses of 12 mg betamethasone, IM. The control group received a placebo of normal saline. | |
| Outcomes | Maternal outcome (maternal death, maternal infections), fetal/neonatal outcomes reported (RDS, birthweight, necrotising enterocolitis, systemic infection in the first 48 h of life, need for mechanical ventilation/CPAP, Apgar < 7 at 5 min, admission to NICU) | |
| Notes | Original article in Persian; we have obtained a truncated translation for this update. Our translator was unable to translate the definition of respiratory distress syndrome but said that the outcome was based on defined symptoms and confirmed by a paediatrician. Additonal outcome data for this trial are: Maternal length of stay > 3 d (equal numbers in treatment arms) is reported narratively above: mean birthweight and SD in kg has been analysed as g. Data for the trial outcome of 'need for respiratory support' has been included in the review analysis 1.26 'need for mechanical ventilation'. We have been unable to confirm whether the trial included only singleton pregnancy, but this is suggested by the equal numbers of women and infants reported. We have included data from this trial in the singleton subgroup. We had no information about membrane status from our translation, and so this trial has been included in the 'not reported or mixed population subgroup.' Maternal length of stay > 3 d (equal numbers in both arms) is reported narratively. We emailed study investigators for clarification and additional information with no reply (2/2016). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Generation of sequence not stated, but block method specified |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) | Low risk | Trial described as double‐blind. Placebo‐controlled trial, and researchers and women were blind to treatment |
| Blinding of outcome assessment (detection bias) | Low risk | Neonatal outcomes extracted by blinded paediatrician. |
| Incomplete outcome data (attrition bias) | Low risk | Data reported for all women randomised |
| Selective reporting (reporting bias) | Low risk | Relevant outcome data reported |
| Other bias | Unclear risk | We have obtained a basic translation, but future correspondence with authors may clarify some of the risk of bias domains above. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 3 hospitals in Florida, USA | |
| Interventions | 4 treatment arms. Group 1, expectant management. Group 2, expectant management plus 2 doses of 12 mg betamethasone IM 24 h apart, repeated weekly if the women remained undelivered. Group 3, expectant management plus 2 g ampicillin IV every 6 h until cervical cultures were negative. Group 4, combination of group 2 and 3 management. We combined Groups 2 and 4 in the treatment arm for the review, and groups 1 and 3 in the control arm for the review. | |
| Outcomes | Maternal outcome (chorioamnionitis), fetal/neonatal outcomes reported (neonatal death, RDS, chronic lung disease, IVH, birthweight, proven neonatal infection while in NICU, necrotising enterocolitis, duration of mechanical ventilation/CPAP) | |
| Notes | Further information requested from study authors but there was no reply. No information was available on post‐randomisation exclusions | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | "Sealed envelopes" were used. Not further described |
| Blinding of participants and personnel (performance bias) | High risk | As comparison was expectant management, blinding of participants and personnel was not possible |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment was not described |
| Incomplete outcome data (attrition bias) | Unclear risk | No losses to follow‐up noted. No information was available on post‐randomisation exclusions as per exclusion criteria |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Wake Forest University Medical Center, North Carolina, USA | |
| Interventions | 3 treatment arms. Group 1, 2 doses of 6 mg or 12 mg betamethasone IM 12 h apart, delivery 24‐48 h after PROM and after 24 h of corticosteroid therapy. Group 2, delivery 24‐48 h after PROM. Group 3, expectant management. We did not include Group 3 in the review. | |
| Outcomes | Fetal/neonatal outcomes (neonatal death, RDS, proven neonatal infection while in NICU) and health service outcome reported (length of neonatal hospitalisation) | |
| Notes | Authors provided further information | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random‐number table generated randomisation sequence |
| Allocation concealment (selection bias) | Unclear risk | Consecutive sealed envelopes were used, not stated if opaque |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel was not possible due to the nature of the comparison. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment was not described. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up or exclusions |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: University of Illinois, Chicago, USA | |
| Interventions | The treatment group received 2 doses of 12 mg betamethasone IM 12 h apart repeated weekly until 32 weeks. | |
| Outcomes | Fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, systemic infection in the first 48 h of life, proven neonatal infection while in NICU) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel was not possible due to the nature of the comparison. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment was not described. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up or exclusions described |
| Selective reporting (reporting bias) | Low risk | Pre‐specified outcomes were reported. |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT Stratification: not stated | |
| Participants | Location: Instituto de Medicina Integral Professor Fernando Figueira, Recife, Pernambuco, Brazil | |
| Interventions | The treatment group received 2 doses of 12 mg IM betamethasone 24 h apart. The control group received IM saline as placebo. | |
| Outcomes | Maternal outcomes (side effects of therapy in women) and fetal/neonatal outcomes (fetal deaths, neonatal deaths, RDS, birthweight, proven infection while in NICU, need for mechanical ventilation/CPAP, mean duration of mechanical ventilation/CPAP, surfactant use, small for gestational age, admission to NICU) | |
| Notes | For infant outcomes we have used the denominator stated in the published report excluding women who left the trial pregnant. An intention‐to‐treat analysis should have included these women, so for SOF outcomes we carried out a sensitivity analysis to determine if the denominator used made a difference to the overall pooled effect estimate; it did not (data not shown) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random number table was prepared by a statistician not involved in the study, using random allocation software |
| Allocation concealment (selection bias) | Low risk | The hospital pharmacy prepared sealed cardboard boxes numbered according to the random number table, and containing either betamethasone or placebo, identical in appearance, volume and colour. |
| Blinding of participants and personnel (performance bias) | Low risk | Investigators, physicians caring for the women, the women themselves and the statistician were all blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Investigators, physicians caring for the women, the women themselves and the statistician were all blinded. |
| Incomplete outcome data (attrition bias) | Unclear risk | 43 (13%) women (19 in steroid group and 24 in placebo group) were discharged from hospital still pregnant and were considered post‐randomisation losses to follow‐up. 2 (1%) women were excluded from the placebo group as they were found to be ineligible after randomisation (multiple pregnancy, and term pregnancy). |
| Selective reporting (reporting bias) | Low risk | All pre‐specified outcomes appear to have been reported. |
| Other bias | Unclear risk | States "no significant differences between groups in most baseline characteristics," but does not report where differences exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: 2 military hospitals in Jordan | |
| Interventions | The treatment group received 4 doses of 6 mg dexamethasone IM 12 h apart, repeated if women had not delivered after 1 week. | |
| Outcomes | Maternal outcomes (chorioamnionitis, endometritis), fetal/neonatal outcomes (fetal death, neonatal death, RDS, IVH, proven neonatal infection while in NICU, necrotising enterocolitis, Apgar < 7) and health service outcome reported (length of neonatal hospitalisation) | |
| Notes | Study authors contacted for further information but no reply. Discrepancy in number of infants with necrotising enterocolitis in manuscript | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random‐number table generated randomisation sequence. |
| Allocation concealment (selection bias) | Unclear risk | Method of allocation concealment not stated |
| Blinding of participants and personnel (performance bias) | High risk | Blinding of participants and personnel was not possible due to the nature of the comparison. |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessment was not described. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up or exclusions stated |
| Selective reporting (reporting bias) | Unclear risk | Discrepancy in number of infants with necrotising enterocolitis in manuscript |
| Other bias | Unclear risk | Funding source not stated |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Department of Obstetrics and Gynaecology and Department of Neonatology, Wilhelmina Gasthuis, University of Amsterdam, Amsterdam, the Netherlands. | |
| Interventions | The treatment group received 8 mg betamethasone phosphate and 6 mg betamethasone acetate IM repeated after 24 h. All women received orciprenaline infusion and bed‐rest until 32 weeks. | |
| Outcomes | Maternal outcomes (death, chorioamnionitis, maternal infections, fever after trial entry requiring antibiotics, intrapartum fever requiring antibiotics, postnatal fever, admission to ICU, side effects of therapy), fetal/neonatal outcomes (fetal death, neonatal death, RDS, IVH, birthweight, Apgar score < 7), childhood outcomes (weight, height, head circumference, lung function, visual impairment, hearing impairment, intellectual impairment, cerebral palsy, behavioural/learning difficulties) and adulthood outcomes were reported (weight, height, head circumference, blood pressure, intellectual impairment, age at puberty) | |
| Notes | Initial study report included a third arm of women (n = 133) and infants (n = 164) who had been excluded from randomisation because they were: 1. already in labour (n = 80) and could not be prolonged for at least 12 h or were already 33 weeks' gestation, or; 2. (n = 53) contra‐indicated for corticosteroids, or; 3. wrongly excluded (n = 5). These women and infants are not included in the review. Two perinatal deaths in the corticosteroid treatment arm were excluded for: 1. intrauterine fetal death due to solutio placentae, and 2. death due to prolapsed umbilical cord. These deaths have been included in the analyses. Infections in infants are listed in Table 6 of the Schutte 1979 original report. There are deaths associated with these infections, and it is not clear when these infections or deaths occurred, or if they have been included in the reported numbers for neonatal or perinatal deaths. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Low risk | Coded drug ampoules prepared by pharmacist |
| Blinding of participants and personnel (performance bias) | Low risk | Trial described as double blind, with pharmacist preparing identical treatment and control ampoules |
| Blinding of outcome assessment (detection bias) | Low risk | Staff were blind to treatment group |
| Incomplete outcome data (attrition bias) | Unclear risk | 2 perinatal deaths in the corticosteroids group were excluded. Data for infant infections specify additional deaths, and it is unclear whether or not these deaths are counted in the overall total for perinatal deaths. The inclusion of these deaths will not change the overall conclusions of meta‐analysis in favour of corticosteroid use |
| Selective reporting (reporting bias) | Low risk | Primary outcome of the trial was RDS; this and other important outcomes are reported |
| Other bias | Unclear risk | We are unclear as to the impact of exclusions on results, especially for the outcome of perinatal deaths. |
| Study characteristics | ||
| Methods | Type of study: RCT Stratification: not stated | |
| Participants | Location: Barnes‐Jewish Hospital, St Louis, Missouri, USA | |
| Interventions | The treatment group received either 2 doses of betamethasone 12 mg IM 24 h apart, or 4 doses of dexamethasone 6 mg IM 12 h apart. The control group received no treatment. | |
| Outcomes | Maternal outcomes (side effects of therapy in women) and fetal/neonatal outcomes (need for mechanical ventilation/CPAP, admission to NICU) | |
| Notes | This study was stopped early due to difficulties in participant recruitment | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Randomly assigned" not further described |
| Allocation concealment (selection bias) | Unclear risk | "Sealed envelopes" not further described |
| Blinding of participants and personnel (performance bias) | High risk | Control group received no treatment so blinding of participants and study personnel would not have been possible |
| Blinding of outcome assessment (detection bias) | Unclear risk | No mention is made of blinding of outcome assessors |
| Incomplete outcome data (attrition bias) | High risk | 7 (22%) women (3 in the study group and 4 in the control group) delivered within 7 d of their initial testing for fetal lung maturity and were excluded from the analysis. No intention‐to‐treat analysis |
| Selective reporting (reporting bias) | High risk | Hyaline membrane disease is listed as an outcome, but not reported |
| Other bias | High risk | This study was stopped early due to difficulties in patient recruitment |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: Northwestern University Medical School, Chicago, Illinois, USA | |
| Interventions | The treatment group received 4 doses of 5 mg dexamethasone IM 12 h apart, repeated weekly if the women remained undelivered. All infants born < 30 weeks received prophylactic surfactant at birth. | |
| Outcomes | Maternal outcomes (chorioamnionitis, endometritis) and fetal/neonatal outcomes reported (neonatal death, RDS, chronic lung disease, IVH, small‐for‐gestational age, birthweight, necrotising enterocolitis) | |
| Notes | Those women undelivered after 29 weeks were eligible for corticosteroid outside the study protocol. These women and their infants are not included in the review as it was not possible to separate out control women who subsequently received corticosteroids | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation sequence used |
| Allocation concealment (selection bias) | Low risk | Pharmacy provided identical syringes labelled with the woman's study number. |
| Blinding of participants and personnel (performance bias) | Low risk | "Clinical personnel and the patient were effectively blinded to study group assignment" |
| Blinding of outcome assessment (detection bias) | Low risk | The severity of RDS, and diagnosis of IVH were "confirmed independently by chart reviews conducted by 1 of the authors blinded to study group assignment" |
| Incomplete outcome data (attrition bias) | Unclear risk | 49 (40%) of the 124 women initially recruited, remained undelivered after 29 weeks and were not included in the review. |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT Stratification: yes, by gestational age at entry | |
| Participants | Location: 2 hospitals in Boston, USA | |
| Interventions | The treatment group received 6 doses of 4 mg dexamethasone phosphate IM 8 h apart. | |
| Outcomes | Maternal outcomes (endometritis, fever after trial entry requiring antibiotics) and fetal/neonatal outcomes reported (fetal death, neonatal death, RDS, chronic lung disease, IVH, proven neonatal infection while in NICU) | |
| Notes | Study authors contacted for further information but there was no reply | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Coded drug boxes were used, but it is not clear how they were coded, e.g. if they were sequentially numbered. |
| Blinding of participants and personnel (performance bias) | Low risk | It is likely that participants were blinded due to the use of an identical looking placebo. Blinding of study personnel was not described. |
| Blinding of outcome assessment (detection bias) | Low risk | Diagnosis of RDS was made prior to breaking the treatment code. |
| Incomplete outcome data (attrition bias) | Unclear risk | Data not available for maternal outcomes on 4 (3%) women (2 in each treatment arm) with no explanation given. |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | Insufficient information to asses if other sources of bias exist. |
| Study characteristics | ||
| Methods | Type of study: RCT | |
| Participants | Location: University of Helsinki, Finland | |
| Interventions | The treatment group received 2 doses of 12 mg betamethasone IM 24 h apart. | |
| Outcomes | Fetal/neonatal outcomes reported (RDS, HPA axis function) | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not stated |
| Allocation concealment (selection bias) | Unclear risk | Coded drug boxes were used but it is not clear how they were coded, e.g. if they were sequentially numbered. |
| Blinding of participants and personnel (performance bias) | Low risk | It is likely that participants were blinded due to the use of a placebo "similar in appearance" to the corticosteroid. Blinding of study personnel was not described other than "ampoules were administered to the patients using the double‐blind principle". |
| Blinding of outcome assessment (detection bias) | Unclear risk | Blinding of outcome assessors was not described. |
| Incomplete outcome data (attrition bias) | Low risk | No losses to follow‐up or exclusions stated |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, but appears to report on all pre‐specified outcomes |
| Other bias | Unclear risk | The study was discontinued early because the overall incidence of RDS was too low for any meaningful conclusions concerning the efficacy of prevention. |
CPAP: continuous positive airways pressure
GDM: gestational diabetes mellitus
HPA: hypothalamic‐pituitary‐adrenal
ICU: intensive care unit
IM: intramuscular
IUGR: Iintrauterine growth restriction
IV: intravenous
IVH: intraventricular haemorrhage
LMP: last menstrual period
NICU: neonatal intensive care unit
PIH: pregnancy induced hypertension
PROM: premature rupture of membranes
PPROM: prolonged premature rupture of membranes
RCT: randomised controlled trial
RDS: respiratory distress syndrome
Rh: Rhesus
SD: standard deviation
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| This abstract compares TRH + betamethasone with betamethasone + placebo. | |
| This is a trial of strategies to optimise use of corticosteroids. | |
| This study is quasi‐experimental. | |
| Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately. | |
| This abstract compares TRH + betamethasone with betamethasone + placebo. | |
| This trial compares oral vs IM dexamethasone in the prevention of RDS. It does not meet our entry criteria for inclusion of studies for the review. | |
| This trial compares a policy of corticosteroid therapy followed by elective delivery with a policy of withholding corticosteroids and awaiting delivery so the independent effect of the 2 co‐interventions cannot be evaluated separately. | |
| Not a randomised trial. Outcomes for women who received steroids were compared with those that did not. Information obtained from translation sheet. Original article in Bosnian | |
| Not a randomised trial. Women were allocated to placebo if they were expected to deliver within 24 h and to betamethasone if labour was not expected within 24 h. | |
| Corticosteroid therapy (hydrocortisone) and co‐intervention of elective delivery was compared to expectant management in PROM. The independent effect of the 2 co‐interventions cannot be evaluated separately. | |
| Compared different doses of corticosteroid: 12‐hourly vs 24‐hourly. The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015. | |
| The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015. | |
| Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately. | |
| The study includes a repeat dose of corticosteroids and is eligible for inclusion in a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015. | |
| Quasi‐randomised study that allocated women according to the in‐patient sequence. Compared the effect of dexamethasone combined with vitamin K, dexamethasone alone and no dexamethasone or vitamin K on periventricular/intraventricular haemorrhage. | |
| This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate. | |
| This study appears to be an observational study of 163 premature infants, 80 of whom were exposed to antenatal corticosteroids, and 83 of whom were not. | |
| This trial compares repeat dose corticosteroids and is eligible for inclusion a different review, 'Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes' Crowther 2015. | |
| This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate. | |
| Quasi‐randomised using medical record number. | |
| This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions and the fact that it was possibly quasi‐randomised. | |
| This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate. | |
| This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions. Of 146 babies included in the study, the paper only reports outcomes for 61. | |
| This is a head‐to‐head trial of 2 different regimens and is eligible for the Cochrane review entitled 'Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth' Brownfoot 2013. | |
| This study compares the effects of betamethasone vs dexamethasone on antenatal fetal heart rate. | |
| This study was included in original review. It is excluded from this update because of > 20% post‐randomisation exclusions. The paper only reports results from 92 of 144 randomised mothers and 97 of 149 randomised babies. | |
| Quasi‐randomised study. Randomised participants are combined with a non‐randomised cohort and cannot be analysed separately. | |
| This trial compares IM betamethasone with IV cortisol. It does not meet our entry criteria for inclusion of studies for the review. |
IM: intramuscular
IV: intravenous
PROM: premature rupture of membranes
RDS: respiratory distress syndrome
TRH: thyrotropin‐releasing hormone
vs: versus
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Maternal death Show forest plot | 5 | 3392 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.06, 15.50] |
| Analysis 1.1  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death | ||||
| 1.2 Chorioamnionitis Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| Analysis 1.2  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis | ||||
| 1.3 Endometritis Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.20 [0.87, 1.63] |
| Analysis 1.3  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis | ||||
| 1.4 Perinatal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| Analysis 1.4  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths | ||||
| 1.5 Neonatal deaths Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 1.5  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths | ||||
| 1.6 Fetal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 1.6  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths | ||||
| 1.7 Respiratory distress syndrome Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.56, 0.77] |
| Analysis 1.7  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome | ||||
| 1.8 Moderate/severe respiratory distress syndrome Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| Analysis 1.8  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome | ||||
| 1.9 Chronic lung disease Show forest plot | 6 | 818 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.42, 1.79] |
| Analysis 1.9  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease | ||||
| 1.10 Intraventricular haemorrhage Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.40, 0.76] |
| Analysis 1.10  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage | ||||
| 1.11 Mean birthweight (g) Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| Analysis 1.11  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g) | ||||
| 1.12 Death in childhood Show forest plot | 4 | 1010 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.36, 1.27] |
| Analysis 1.12  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood | ||||
| 1.13 Neurodevelopmental delay in childhood Show forest plot | 1 | 82 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.14, 2.98] |
| Analysis 1.13  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood | ||||
| 1.14 Death into adulthood Show forest plot | 1 | 988 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.56, 1.81] |
| Analysis 1.14  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood | ||||
| 1.15 Fever in women after trial entry requiring the use of antibiotics Show forest plot | 4 | 481 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.43, 2.06] |
| Analysis 1.15  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics | ||||
| 1.16 Intrapartum fever in woman requiring the use of antibiotics Show forest plot | 2 | 319 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.09, 4.89] |
| Analysis 1.16  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics | ||||
| 1.17 Side effects of therapy in women Show forest plot | 6 | 3572 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.82] |
| Analysis 1.17  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women | ||||
| 1.18 Admission into adult intensive care unit Show forest plot | 2 | 319 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.74 [0.26, 2.05] |
| Analysis 1.18  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit | ||||
| 1.19 Hypertension Show forest plot | 1 | 220 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.36, 2.76] |
| Analysis 1.19  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension | ||||
| 1.20 Postnatal fever in woman Show forest plot | 5 | 1323 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.64, 1.33] |
| Analysis 1.20  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman | ||||
| 1.21 Glucose intolerance Show forest plot | 1 | 123 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.71 [1.14, 6.46] |
| Analysis 1.21  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance | ||||
| 1.22 Necrotising enterocolitis Show forest plot | 10 | 4702 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.32, 0.78] |
| Analysis 1.22  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis | ||||
| 1.23 Systemic infection in the first 48 hours of life Show forest plot | 8 | 1753 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.41, 0.88] |
| Analysis 1.23  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life | ||||
| 1.24 Proven infection while in the neonatal intensive care unit Show forest plot | 13 | 5707 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.55, 1.08] |
| Analysis 1.24  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit | ||||
| 1.25 Need for mechanical ventilation/CPAP Show forest plot | 9 | 1368 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.56, 0.84] |
| Analysis 1.25  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP | ||||
| 1.26 Mean duration of mechanical ventilation/CPAP (days) Show forest plot | 3 | 471 | Mean Difference (IV, Random, 95% CI) | ‐1.91 [‐4.59, 0.76] |
| Analysis 1.26  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days) | ||||
| 1.27 Mean duration of oxygen supplementation (days) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.27  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days) | ||||
| 1.28 Surfactant use Show forest plot | 5 | 3556 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.51, 0.90] |
| Analysis 1.28  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use | ||||
| 1.29 Air leak syndrome Show forest plot | 2 | 2965 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.76 [0.32, 1.80] |
| Analysis 1.29  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome | ||||
| 1.30 Apgar < 7 at 5 minutes Show forest plot | 10 | 2419 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.67, 0.98] |
| Analysis 1.30  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes | ||||
| 1.31 Mean interval between trial entry and birth (days) Show forest plot | 3 | 1513 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐1.86, 2.32] |
| Analysis 1.31  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days) | ||||
| 1.32 Small‐for‐gestational age Show forest plot | 5 | 3478 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.96, 1.28] |
| Analysis 1.32  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age | ||||
| 1.33 Mean infant HPA axis function (cortisol) Show forest plot | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 3.94 [‐3.12, 11.00] |
| Analysis 1.33  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol) | ||||
| 1.33.1 In babies born < 24 hours after 1st dose | 1 | 6 | Mean Difference (IV, Fixed, 95% CI) | 9.00 [‐11.93, 29.93] |
| 1.33.2 In babies born 24‐48 hours after 1st dose | 1 | 10 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐8.68, 8.68] |
| 1.33.3 In babies born > 48 hours after 1st dose | 1 | 11 | Mean Difference (IV, Fixed, 95% CI) | 13.00 [‐1.90, 27.90] |
| 1.34 Admission to neonatal intensive care unit Show forest plot | 7 | 3803 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.84, 0.97] |
| Analysis 1.34  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit | ||||
| 1.35 Developmental delay in childhood Show forest plot | 2 | 518 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.49 [0.24, 1.00] |
| Analysis 1.35  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood | ||||
| 1.36 Cerebral palsy in childhood Show forest plot | 5 | 904 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.34, 1.03] |
| Analysis 1.36  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood | ||||
| 1.37 Mean childhood weight (kg) Show forest plot | 2 | 333 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.39, 1.00] |
| Analysis 1.37  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg) | ||||
| 1.37.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.32, 1.12] |
| 1.37.2 Schutte (females) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐2.40 [‐6.55, 1.75] |
| 1.37.3 Schutte (males) | 1 | 44 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐3.88, 3.68] |
| 1.38 Mean childhood height (cm) Show forest plot | 2 | 334 | Mean Difference (IV, Fixed, 95% CI) | 1.02 [‐0.26, 2.29] |
| Analysis 1.38  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm) | ||||
| 1.38.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 1.00 [‐0.39, 2.39] |
| 1.38.2 Schutte (females) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | 1.70 [‐3.08, 6.48] |
| 1.38.3 Schutte (males) | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 0.60 [‐3.79, 4.99] |
| 1.39 Mean childhood head circumference (cm) Show forest plot | 2 | 328 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [‐0.08, 0.63] |
| Analysis 1.39  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm) | ||||
| 1.39.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.11, 0.71] |
| 1.39.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐1.05, 0.85] |
| 1.39.3 Schutte (males) | 1 | 42 | Mean Difference (IV, Fixed, 95% CI) | 0.60 [‐0.51, 1.71] |
| 1.40 Mean childhood VC (% predicted) Show forest plot | 2 | 150 | Mean Difference (IV, Fixed, 95% CI) | ‐1.68 [‐5.12, 1.75] |
| Analysis 1.40  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted) | ||||
| 1.40.1 Liggins | 1 | 75 | Mean Difference (IV, Fixed, 95% CI) | 0.70 [‐5.12, 6.52] |
| 1.40.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐2.60 [‐8.65, 3.45] |
| 1.40.3 Schutte (males) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐3.30 [‐9.27, 2.67] |
| 1.41 Mean childhood FEV1 (% predicted) Show forest plot | 1 | 75 | Mean Difference (IV, Fixed, 95% CI) | ‐4.73 [‐10.13, 0.67] |
| Analysis 1.41  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted) | ||||
| 1.41.1 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐2.50 [‐11.24, 6.24] |
| 1.41.2 Schutte (males) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐6.10 [‐12.96, 0.76] |
| 1.42 Mean childhood FEV1/VC Show forest plot | 2 | 150 | Mean Difference (IV, Random, 95% CI) | ‐0.94 [‐3.63, 1.76] |
| Analysis 1.42  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC | ||||
| 1.42.1 Liggins | 1 | 75 | Mean Difference (IV, Random, 95% CI) | 1.00 [‐2.57, 4.57] |
| 1.42.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Random, 95% CI) | 0.00 [‐5.56, 5.56] |
| 1.42.3 Schutte (males) | 1 | 39 | Mean Difference (IV, Random, 95% CI) | ‐3.00 [‐6.14, 0.14] |
| 1.43 Mean childhood systolic blood pressure (mmHg) Show forest plot | 1 | 223 | Mean Difference (IV, Fixed, 95% CI) | ‐1.60 [‐4.06, 0.86] |
| Analysis 1.43  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg) | ||||
| 1.44 Visual impairment in childhood Show forest plot | 2 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.24, 1.23] |
| Analysis 1.44  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood | ||||
| 1.45 Hearing impairment in childhood Show forest plot | 2 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.04, 9.87] |
| Analysis 1.45  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood | ||||
| 1.46 Intellectual impairment in childhood Show forest plot | 3 | 778 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.44, 1.69] |
| Analysis 1.46  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood | ||||
| 1.47 Behavioural/learning difficulties in childhood Show forest plot | 1 | 90 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.35, 2.09] |
| Analysis 1.47  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood | ||||
| 1.48 Mean adult insulin (log values) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.48  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values) | ||||
| 1.48.1 Fasting | 1 | 435 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [‐0.03, 0.19] |
| 1.48.2 30 minutes following a 75 g oral glucose tolerance test | 1 | 412 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [0.04, 0.28] |
| 1.48.3 120 minutes following a 75 g oral glucose tolerance test | 1 | 428 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.27, 0.07] |
| 1.49 Mean adult glucose (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.49  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L) | ||||
| 1.49.1 Fasting | 1 | 432 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.09, 0.11] |
| 1.49.2 30 minutes following a 75 g oral glucose tolerance test | 1 | 413 | Mean Difference (IV, Fixed, 95% CI) | 0.19 [‐0.14, 0.52] |
| 1.49.3 120 minutes following a 75 g oral glucose tolerance test | 1 | 410 | Mean Difference (IV, Fixed, 95% CI) | ‐0.27 [‐0.52, ‐0.02] |
| 1.50 Mean adult weight (kg) Show forest plot | 2 | 538 | Mean Difference (IV, Random, 95% CI) | ‐0.83 [‐6.41, 4.76] |
| Analysis 1.50  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg) | ||||
| 1.50.1 Schutte (females) | 1 | 37 | Mean Difference (IV, Random, 95% CI) | ‐6.00 [‐12.93, 0.93] |
| 1.50.2 Schutte (males) | 1 | 43 | Mean Difference (IV, Random, 95% CI) | ‐1.00 [‐9.91, 7.91] |
| 1.50.3 Liggins | 1 | 458 | Mean Difference (IV, Random, 95% CI) | 2.57 [‐0.72, 5.86] |
| 1.51 Mean adult height (cm) Show forest plot | 2 | 537 | Mean Difference (IV, Fixed, 95% CI) | 0.91 [‐0.28, 2.10] |
| Analysis 1.51  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm) | ||||
| 1.51.1 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐1.00 [‐5.37, 3.37] |
| 1.51.2 Schutte (males) | 1 | 43 | Mean Difference (IV, Fixed, 95% CI) | 3.00 [‐2.30, 8.30] |
| 1.51.3 Liggins (females) | 1 | 234 | Mean Difference (IV, Fixed, 95% CI) | 1.17 [‐0.65, 2.99] |
| 1.51.4 Liggins (males) | 1 | 224 | Mean Difference (IV, Fixed, 95% CI) | 0.75 [‐1.03, 2.53] |
| 1.52 Mean adult head circumference (cm) Show forest plot | 2 | 537 | Mean Difference (IV, Fixed, 95% CI) | 0.03 [‐0.33, 0.38] |
| Analysis 1.52  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm) | ||||
| 1.52.1 Schutte (females) | 1 | 37 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐1.03, 1.03] |
| 1.52.2 Schutte (males) | 1 | 42 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐1.37, 0.97] |
| 1.52.3 Liggins | 1 | 458 | Mean Difference (IV, Fixed, 95% CI) | 0.06 [‐0.34, 0.46] |
| 1.53 Mean adult skinfold thickness (log values) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.53  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values) | ||||
| 1.53.1 Triceps | 1 | 456 | Mean Difference (IV, Fixed, 95% CI) | ‐0.02 [‐0.11, 0.07] |
| 1.53.2 Biceps | 1 | 456 | Mean Difference (IV, Fixed, 95% CI) | ‐0.01 [‐0.11, 0.09] |
| 1.53.3 Subscapular | 1 | 441 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.08, 0.10] |
| 1.53.4 Suprailiac | 1 | 452 | Mean Difference (IV, Fixed, 95% CI) | ‐0.01 [‐0.12, 0.10] |
| 1.54 Mean adult systolic blood pressure (mmHg) Show forest plot | 2 | 545 | Mean Difference (IV, Random, 95% CI) | ‐1.53 [‐4.50, 1.44] |
| Analysis 1.54  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg) | ||||
| 1.54.1 Schutte (females) | 1 | 38 | Mean Difference (IV, Random, 95% CI) | ‐4.00 [‐9.12, 1.12] |
| 1.54.2 Schutte (males) | 1 | 52 | Mean Difference (IV, Random, 95% CI) | ‐3.00 [‐7.17, 1.17] |
| 1.54.3 Liggins | 1 | 455 | Mean Difference (IV, Random, 95% CI) | 0.55 [‐1.88, 2.98] |
| 1.55 Mean adult HPA axis function (mean log fasting cortisol) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.55  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol) | ||||
| 1.56 Mean cholesterol in adulthood (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.56  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L) | ||||
| 1.57 Mean age at puberty (years) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.57  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years) | ||||
| 1.57.1 Schutte (females) | 1 | 38 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.94, 0.94] |
| 1.58 Educational achievement by adulthood (university or polytechnic education) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.58  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education) | ||||
| 1.59 Visual impairment in adulthood Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.59  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood | ||||
| 1.60 Hearing impairment in adulthood Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.60  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood | ||||
| 1.61 Intellectual impairment in adulthood Show forest plot | 2 | 273 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.24 [0.01, 4.95] |
| Analysis 1.61  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood | ||||
| 1.62 Mean adult FVC (% predicted) Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | ‐0.70 [‐3.16, 1.76] |
| Analysis 1.62  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted) | ||||
| 1.63 Mean adult FEV1 (% predicted) Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐2.31, 3.11] |
| Analysis 1.63  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted) | ||||
| 1.64 Mean adult FEV1/FVC Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.01, 0.03] |
| Analysis 1.64  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC | ||||
| 1.65 Mean adult PEF Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 2.20 [‐0.77, 5.17] |
| Analysis 1.65  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF | ||||
| 1.66 Mean adult F50 Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 3.00 [‐1.57, 7.57] |
| Analysis 1.66  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50 | ||||
| 1.67 Mean adult F25 Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐3.82, 4.62] |
| Analysis 1.67  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25 | ||||
| 1.68 Mean adult FEF 25%‐75% Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 2.20 [‐2.10, 6.50] |
| Analysis 1.68  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75% | ||||
| 1.69 FEV1/FVC < 70% Show forest plot | 1 | 383 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.49, 1.57] |
| Analysis 1.69  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70% | ||||
| 1.70 Asthma diagnosed by Doctor in lifetime Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 1.70  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime | ||||
| 1.71 Wheezing in last 12 months Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.06 [0.84, 1.35] |
| Analysis 1.71  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months | ||||
| 1.72 Current Asthma Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.74, 1.48] |
| Analysis 1.72  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma | ||||
| 1.73 Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis) Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.33 [0.69, 2.59] |
| Analysis 1.73  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis) | ||||
| 1.74 Spontaneous pneumothorax Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.07, 17.66] |
| Analysis 1.74  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax | ||||
| 1.75 Shortness of breath at anytime in the last 12 months Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.80, 1.31] |
| Analysis 1.75  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months | ||||
| 1.76 Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.04, 0.04] |
| Analysis 1.76  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density | ||||
| 1.77 Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.01, 0.01] |
| Analysis 1.77  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density | ||||
| 1.78 Mean adult total body BMC (grams) bone mineral content Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 18.00 [‐151.30, 187.30] |
| Analysis 1.78  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content | ||||
| 1.79 Mean adult total body aBMD (g/cm3) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.03, 0.03] |
| Analysis 1.79  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density | ||||
| 1.80 Mean adult femoral neck aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.03, 0.07] |
| Analysis 1.80  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density | ||||
| 1.81 Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.02, 0.06] |
| Analysis 1.81  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density | ||||
| 1.82 Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.04, 0.06] |
| Analysis 1.82  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density | ||||
| 1.83 Mean total proximal femur aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.03, 0.07] |
| Analysis 1.83  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density | ||||
| 1.84 Mean length of antenatal hospitalisation (days) Show forest plot | 1 | 218 | Mean Difference (IV, Fixed, 95% CI) | 0.50 [‐1.40, 2.40] |
| Analysis 1.84  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days) | ||||
| 1.85 Mean length of postnatal hospitalisation (days) Show forest plot | 1 | 218 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐1.72, 1.72] |
| Analysis 1.85  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days) | ||||
| 1.86 Mean length of neonatal hospitalisation (days) Show forest plot | 5 | 788 | Mean Difference (IV, Fixed, 95% CI) | 0.18 [‐0.51, 0.87] |
| Analysis 1.86  Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days) | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Chorioamnionitis ‐ single or multiple pregnancy Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| Analysis 2.1  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy | ||||
| 2.1.1 In women delivering singleton pregnancies | 7 | 4682 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.56, 1.01] |
| 2.1.2 In women delivering multiple pregnancies | 1 | 74 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.42 [0.04, 4.49] |
| 2.1.3 Mixed population | 8 | 790 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.70, 1.57] |
| 2.2 Perinatal death ‐ single or multiple pregnancy Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.59, 0.89] |
| Analysis 2.2  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy | ||||
| 2.2.1 In babies born from singleton pregnancies | 6 | 5182 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.54, 1.05] |
| 2.2.2 In babies born from multiple pregnancies | 2 | 252 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.37, 1.47] |
| 2.2.3 Mixed population | 9 | 1295 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.49, 0.94] |
| 2.3 Neonatal death ‐ single or multiple pregnancy Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 2.3  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy | ||||
| 2.3.1 In babies born from singleton pregnancies | 9 | 5335 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.61, 0.92] |
| 2.3.2 In babies born from multiple pregnancies | 2 | 236 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.79 [0.39, 1.61] |
| 2.3.3 Mixed population | 13 | 1617 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.46, 0.78] |
| 2.4 Fetal death ‐ single or multiple pregnancy Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.97 [0.73, 1.29] |
| Analysis 2.4  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy | ||||
| 2.4.1 In babies born from singleton pregnancies | 6 | 5182 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.75, 1.45] |
| 2.4.2 In babies born from multiple pregnancies | 2 | 252 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.53 [0.20, 1.40] |
| 2.4.3 Mixed population | 9 | 1295 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.99 [0.50, 1.99] |
| 2.5 Respiratory distress syndrome ‐ single or multiple pregnancy Show forest plot | 28 | 7762 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.59, 0.78] |
| Analysis 2.5  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy | ||||
| 2.5.1 In babies born from singleton pregnancies | 15 | 6081 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.50, 0.77] |
| 2.5.2 In babies born from multiple pregnancies | 4 | 320 | Risk Ratio (M‐H, Random, 95% CI) | 0.90 [0.67, 1.22] |
| 2.5.3 Mixed population | 13 | 1361 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.53, 0.89] |
| 2.6 IVH ‐ single or multiple pregnancy Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| Analysis 2.6  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy | ||||
| 2.6.1 In babies born from singleton pregnancies | 8 | 4782 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.52 [0.36, 0.75] |
| 2.6.2 In babies born from multiple pregnancies | 1 | 137 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.39 [0.07, 2.06] |
| 2.6.3 Mixed population | 8 | 1174 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.44, 0.81] |
| 2.7 Birthweight ‐ single or multiple pregnancy Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐17.61 [‐39.95, 4.74] |
| Analysis 2.7  Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy | ||||
| 2.7.1 In babies born from singleton pregnancy | 9 | 4948 | Mean Difference (IV, Fixed, 95% CI) | ‐24.12 [‐48.27, 0.03] |
| 2.7.2 In babies born from multiple pregnancies | 1 | 150 | Mean Difference (IV, Fixed, 95% CI) | 82.36 [‐146.23, 310.95] |
| 2.7.3 Mixed population | 7 | 1084 | Mean Difference (IV, Fixed, 95% CI) | 16.77 [‐44.16, 77.69] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Chorioamnionitis ‐ intact or ruptured membranes Show forest plot | 15 | 5517 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.85 [0.67, 1.07] |
| Analysis 3.1  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes | ||||
| 3.1.1 In women with intact membranes at 1st dose | 5 | 1437 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.50, 1.40] |
| 3.1.2 In women with ruptured membranes at 1st dose | 7 | 959 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.69, 1.40] |
| 3.1.3 Not reported or mixed population | 4 | 3121 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.47, 1.06] |
| 3.2 Endometritis ‐ intact or ruptured membranes Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.80, 1.80] |
| Analysis 3.2  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes | ||||
| 3.2.1 In women with intact membranes at 1st dose | 2 | 289 | Risk Ratio (M‐H, Random, 95% CI) | 1.21 [0.37, 4.01] |
| 3.2.2 In women with ruptured membranes at 1st dose | 4 | 477 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.35, 2.97] |
| 3.2.3 Not reported or mixed population | 5 | 3264 | Risk Ratio (M‐H, Random, 95% CI) | 1.31 [0.81, 2.13] |
| 3.3 Perinatal death ‐ intact or ruptured membranes Show forest plot | 15 | 6700 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.60, 0.90] |
| Analysis 3.3  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes | ||||
| 3.3.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1332 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.70, 1.08] |
| 3.3.2 In babies born from pregnancies with ruptured membranes at 1st dose | 4 | 733 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.39, 0.90] |
| 3.3.3 Not reported or mixed population | 8 | 4635 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.49, 1.03] |
| 3.4 Neonatal deaths ‐ intact or ruptured membranes Show forest plot | 22 | 7163 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 3.4  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes | ||||
| 3.4.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1236 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.58, 1.03] |
| 3.4.2 In babies born from pregnancies with ruptured membranes at 1st dose | 8 | 1024 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.46, 0.83] |
| 3.4.3 Not reported or mixed population | 11 | 4903 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.53, 0.88] |
| 3.5 Fetal death ‐ intact or ruptured membranes Show forest plot | 15 | 6634 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.71, 1.26] |
| Analysis 3.5  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes | ||||
| 3.5.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1332 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.09 [0.73, 1.64] |
| 3.5.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 790 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.46, 1.61] |
| 3.5.3 Not reported or mixed population | 7 | 4512 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.44, 1.35] |
| 3.6 RDS ‐ intact or ruptured membranes Show forest plot | 28 | 7738 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.56, 0.76] |
| Analysis 3.6  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes | ||||
| 3.6.1 In babies born from pregnancies with intact membranes at 1st dose | 6 | 1721 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.50, 0.80] |
| 3.6.2 In babies born from pregnancies with ruptured membranes at 1st dose | 12 | 1129 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.55, 0.90] |
| 3.6.3 Not reported or mixed population | 14 | 4888 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.46, 0.81] |
| 3.7 IVH ‐ intact or ruptured membranes Show forest plot | 15 | 5868 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| Analysis 3.7  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes | ||||
| 3.7.1 In babies born from pregnancies with intact membranes at 1st dose | 5 | 1394 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.35, 0.72] |
| 3.7.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 895 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.47 [0.28, 0.79] |
| 3.7.3 Not reported or mixed population | 6 | 3579 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.49, 1.07] |
| 3.8 Birthweight ‐ intact or ruptured membranes Show forest plot | 16 | 6153 | Mean Difference (IV, Fixed, 95% CI) | ‐19.52 [‐41.81, 2.78] |
| Analysis 3.8  Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes | ||||
| 3.8.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1301 | Mean Difference (IV, Fixed, 95% CI) | ‐30.27 [‐100.43, 39.89] |
| 3.8.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 835 | Mean Difference (IV, Fixed, 95% CI) | ‐49.72 [‐113.91, 14.46] |
| 3.8.3 Not reported or mixed population | 8 | 4017 | Mean Difference (IV, Fixed, 95% CI) | ‐13.44 [‐38.71, 11.83] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 RDS Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| Analysis 4.1  Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS | ||||
| 4.1.1 Hypertension syndrome | 5 | 382 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.35, 0.72] |
| 4.1.2 No hypertension syndrome or hypertension syndromes excluded | 9 | 2660 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.58 [0.47, 0.71] |
| 4.1.3 Hypertension not reported separately | 18 | 4722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.66, 0.85] |
| 4.2 Perinatal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.60, 0.92] |
| Analysis 4.2  Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths | ||||
| 4.2.1 Hypertension syndrome | 2 | 313 | Risk Ratio (M‐H, Random, 95% CI) | 0.94 [0.42, 2.10] |
| 4.2.2 No hypertension syndrome or hypertension syndromes excluded | 3 | 1394 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.39, 1.29] |
| 4.2.3 Hypertension not reported separately | 11 | 5022 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.52, 0.93] |
| 4.3 Fetal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 4.3  Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths | ||||
| 4.3.1 Women with hypertension syndrome | 3 | 331 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.73 [0.91, 3.28] |
| 4.3.2 No hypertension syndrome or hypertension syndromes excluded | 4 | 1644 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.73 [0.49, 1.08] |
| 4.3.3 Hypertension not reported separately | 10 | 4754 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.15 [0.67, 1.98] |
| 4.4 Neonatal deaths Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 4.4  Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths | ||||
| 4.4.1 Hypertension syndrome | 2 | 278 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.29, 0.87] |
| 4.4.2 No hypertension syndrome or hypertension syndromes excluded | 3 | 1306 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.61, 1.09] |
| 4.4.3 Hypertension not reported separately | 18 | 5604 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.66 [0.54, 0.82] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Chorioamnionitis ‐ type of steroid Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| Analysis 5.1  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid | ||||
| 5.1.1 In women treated with dexamethasone | 5 | 769 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.35 [0.89, 2.05] |
| 5.1.2 In women treated with betamethasone | 10 | 4777 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.50, 0.90] |
| 5.2 Endometritis ‐ type of steroid Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.81, 1.80] |
| Analysis 5.2  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid | ||||
| 5.2.1 In women treated with dexamethasone | 4 | 536 | Risk Ratio (M‐H, Random, 95% CI) | 1.71 [0.86, 3.43] |
| 5.2.2 In women treated with betamethasone | 6 | 3494 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.63, 1.45] |
| 5.3 Perinatal death ‐ type of steroid Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| Analysis 5.3  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid | ||||
| 5.3.1 In babies treated with dexamethasone | 5 | 1420 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.46, 1.11] |
| 5.3.2 In babies treated with betamethasone | 10 | 5309 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.56, 0.94] |
| 5.4 Neonatal deaths by steroid type Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 5.4  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type | ||||
| 5.4.1 In babies treated with dexamethasone | 6 | 1468 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.55, 0.94] |
| 5.4.2 In babies treated with betamethasone | 16 | 5720 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.55, 0.83] |
| 5.5 Fetal death ‐ type of steroid Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 5.5  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid | ||||
| 5.5.1 In babies treated with dexamethasone | 5 | 1420 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.88 [0.48, 1.60] |
| 5.5.2 In babies treated with betamethasone | 10 | 5309 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.73, 1.39] |
| 5.6 Respiratory distress syndrome ‐ type of steroid Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.56, 0.77] |
| Analysis 5.6  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid | ||||
| 5.6.1 In babies treated with dexamethasone | 7 | 1651 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.61, 0.98] |
| 5.6.2 In babies treated with betamethasone | 20 | 6095 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.50, 0.73] |
| 5.6.3 Steroid type not reported | 1 | 18 | Risk Ratio (M‐H, Random, 95% CI) | 1.62 [0.08, 34.66] |
| 5.7 IVH ‐ type of steroid Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.40, 0.76] |
| Analysis 5.7  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid | ||||
| 5.7.1 In babies treated with dexamethasone | 6 | 897 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.18, 1.26] |
| 5.7.2 In babies treated with betamethasone | 10 | 5196 | Risk Ratio (M‐H, Random, 95% CI) | 0.53 [0.40, 0.72] |
| 5.8 Birthweight ‐ type of steroid Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| Analysis 5.8  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid | ||||
| 5.8.1 In babies treated with dexamethasone | 4 | 686 | Mean Difference (IV, Fixed, 95% CI) | ‐17.04 [‐75.48, 41.41] |
| 5.8.2 In babies treated with betamethasone | 12 | 5496 | Mean Difference (IV, Fixed, 95% CI) | ‐18.71 [‐42.92, 5.50] |
| 5.9 Moderate/severe respiratory distress syndrome ‐ type of steroid Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| Analysis 5.9  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid | ||||
| 5.9.1 Dexamethasone | 2 | 219 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.46, 1.44] |
| 5.9.2 Betamethasone | 4 | 1467 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.27, 0.90] |
| 5.10 Chronic lung disease ‐ type of steroid Show forest plot | 6 | 818 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.42, 1.79] |
| Analysis 5.10  Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid | ||||
| 5.10.1 Dexamethasone | 2 | 219 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.72, 1.90] |
| 5.10.2 Betamethasone | 4 | 599 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.26, 2.28] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Chorioamnionitis ‐ decade of trial Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| Analysis 6.1  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial | ||||
| 6.1.1 In women from trials conducted in 1970s | 2 | 1237 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.74 [0.46, 1.17] |
| 6.1.2 In women from trials conducted in 1980s | 3 | 276 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.25, 1.01] |
| 6.1.3 In women from trials conducted in 1990s | 6 | 755 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.18 [0.80, 1.74] |
| 6.1.4 in women from trials conducted in the 2000's | 2 | 257 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.02 [0.59, 6.95] |
| 6.1.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.35, 1.07] |
| 6.2 Endometritis ‐ decade of trial Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.20 [0.87, 1.63] |
| Analysis 6.2  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial | ||||
| 6.2.1 In women from trials conducted in 1970s | 2 | 219 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.86 [0.81, 4.27] |
| 6.2.2 In women from trials conducted in 1980s | 1 | 71 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.30 [0.88, 6.06] |
| 6.2.3 In women from trials conducted in 1990s | 4 | 574 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.53, 1.44] |
| 6.2.4 In women from trials conducted in the 2000's | 3 | 3166 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.18 [0.69, 2.01] |
| 6.3 Perinatal deaths ‐ decade of trial Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| Analysis 6.3  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial | ||||
| 6.3.1 In babies from trials conducted in 1970s | 6 | 1994 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.50, 1.00] |
| 6.3.2 In babies from trials conducted in 1980s | 3 | 879 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.74, 1.42] |
| 6.3.3 In babies from trials conducted in 1990s | 3 | 615 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.43, 0.93] |
| 6.3.4 in babies from trials conducted in 2000's | 2 | 414 | Risk Ratio (M‐H, Random, 95% CI) | 0.47 [0.31, 0.70] |
| 6.3.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Random, 95% CI) | 4.91 [0.24, 102.09] |
| 6.4 Neonatal deaths decade of trial Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 6.4  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial | ||||
| 6.4.1 In babies from trials conducted in 1970s | 7 | 1968 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.56, 0.92] |
| 6.4.2 In babies from trials conducted in 1980s | 6 | 1096 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.70, 1.37] |
| 6.4.3 In babies from trials conducted in 1990s | 5 | 758 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.36, 0.84] |
| 6.4.4 In babies from trials conducted in 2000s | 3 | 539 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.44 [0.31, 0.64] |
| 6.4.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 6.5 Fetal death ‐ decade of trial Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 6.5  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial | ||||
| 6.5.1 In babies from trials conducted in 1970s | 6 | 1994 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.95 [0.67, 1.34] |
| 6.5.2 In babies from trials conducted in 1980s | 3 | 879 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.52, 2.00] |
| 6.5.3 In babies from trials conducted in 1990s | 3 | 615 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.49, 2.36] |
| 6.5.4 In babies from trials conducted in 2000's | 2 | 414 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.19, 4.50] |
| 6.5.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.6 RDS ‐ decade of trial Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| Analysis 6.6  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial | ||||
| 6.6.1 In babies from trials conducted in 1970s | 7 | 1939 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.54 [0.43, 0.69] |
| 6.6.2 In babies from trials conducted in 1980s | 7 | 1167 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.59, 0.88] |
| 6.6.3 In babies from trials conducted in 1990s | 7 | 798 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.65, 0.91] |
| 6.6.4 In babies from trials conducted in 2000s | 5 | 839 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.39 [0.26, 0.59] |
| 6.6.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.80 [0.61, 1.04] |
| 6.7 IVH ‐ decade of trial Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| Analysis 6.7  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial | ||||
| 6.7.1 In babies from trials conducted in 1970s | 4 | 1646 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.29, 0.85] |
| 6.7.2 In babies from trials conducted in 1980s | 2 | 238 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.39, 0.94] |
| 6.7.3 In babies from trials conducted in 1990s | 5 | 722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.42, 0.87] |
| 6.7.4 In babies from trials conducted in 2000s | 3 | 466 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.33 [0.15, 0.73] |
| 6.7.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 6.8 Birthweight ‐ decade of trial Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| Analysis 6.8  Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial | ||||
| 6.8.1 In babies from trials conducted in 1970s | 4 | 1739 | Mean Difference (IV, Fixed, 95% CI) | ‐9.54 [‐83.55, 64.47] |
| 6.8.2 In babies from trials conducted in 1980s | 3 | 280 | Mean Difference (IV, Fixed, 95% CI) | ‐19.60 [‐108.55, 69.35] |
| 6.8.3 In babies from trials conducted in 1990s | 4 | 569 | Mean Difference (IV, Fixed, 95% CI) | ‐33.13 [‐102.39, 36.13] |
| 6.8.4 In babies from trials conducted in 2000s | 3 | 573 | Mean Difference (IV, Fixed, 95% CI) | ‐20.77 [‐61.95, 20.41] |
| 6.8.5 In trials in 2010s | 2 | 3021 | Mean Difference (IV, Fixed, 95% CI) | ‐15.18 [‐48.66, 18.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Chorioamnionitis ‐ Protocol with weekly repeats Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| Analysis 7.1  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats | ||||
| 7.1.1 In women treated with single courses only | 7 | 4659 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.61, 1.11] |
| 7.1.2 In women treated with courses including weekly repeats | 8 | 887 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.57, 1.25] |
| 7.2 Endometritis ‐ protocol with weekly repeats Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.81, 1.80] |
| Analysis 7.2  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats | ||||
| 7.2.1 In women treated with single courses only | 5 | 3450 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.66, 1.64] |
| 7.2.2 In women treated with courses including weekly repeats | 5 | 580 | Risk Ratio (M‐H, Random, 95% CI) | 1.46 [0.72, 2.95] |
| 7.3 Perinatal death ‐ protocol with weekly repeats Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| Analysis 7.3  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats | ||||
| 7.3.1 In babies treated with single course only | 11 | 6250 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.61, 0.99] |
| 7.3.2 In babies treated with courses including weekly repeats | 4 | 479 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.44, 0.97] |
| 7.4 Neonatal death ‐ protocol with weekly repeats Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| Analysis 7.4  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats | ||||
| 7.4.1 In babies treated with single course only | 14 | 6266 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.78 [0.63, 0.95] |
| 7.4.2 In babies treated with courses including weekly repeats | 8 | 922 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.43, 0.72] |
| 7.5 Fetal death ‐ protocol with weekly repeats Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| Analysis 7.5  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats | ||||
| 7.5.1 In babies treated with single course only | 11 | 6250 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.68, 1.25] |
| 7.5.2 In babies treated with courses including weekly repeats | 4 | 479 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [0.64, 2.87] |
| 7.6 RDS ‐ protocol with weekly repeats Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| Analysis 7.6  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats | ||||
| 7.6.1 In babies treated with single course only | 19 | 6818 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.61, 0.79] |
| 7.6.2 In babies treated with courses including weekly repeats | 9 | 946 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.52, 0.72] |
| 7.7 IVH‐ protocol with weekly repeats Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| Analysis 7.7  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats | ||||
| 7.7.1 In babies treated with single course only | 9 | 5216 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.33, 0.76] |
| 7.7.2 In babies treated with courses including weekly repeats | 7 | 877 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.59 [0.45, 0.78] |
| 7.8 Birthweight ‐ protocol with weekly repeats Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| Analysis 7.8  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats | ||||
| 7.8.1 In babies treated with single course only | 12 | 5773 | Mean Difference (IV, Fixed, 95% CI) | ‐18.24 [‐42.12, 5.65] |
| 7.8.2 In babies treated with courses including weekly repeats | 4 | 409 | Mean Difference (IV, Fixed, 95% CI) | ‐20.10 [‐83.79, 43.60] |
| 7.9 Moderate/severe respiratory distress syndrome Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| Analysis 7.9  Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome | ||||
| 7.9.1 Single course | 3 | 1259 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.44, 0.83] |
| 7.9.2 Weekly repeats | 3 | 427 | Risk Ratio (M‐H, Random, 95% CI) | 0.41 [0.13, 1.32] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Chorioamnionitis ‐ gestational age at trial entry Show forest plot | 15 | 5506 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.82 [0.65, 1.05] |
| Analysis 8.1  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry | ||||
| 8.1.1 Less than or equal to 35 weeks + 0 days | 13 | 2304 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.91 [0.70, 1.19] |
| 8.1.2 Greater than or equal to 34 weeks + 0 days | 3 | 3202 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.57 [0.33, 0.99] |
| 8.2 Perinatal death ‐ gestational age at trial entry Show forest plot | 15 | 6687 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.59, 0.88] |
| Analysis 8.2  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry | ||||
| 8.2.1 Less than or equal to 35 weeks + 0 days | 13 | 3391 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.58, 0.87] |
| 8.2.2 Greater than or equal to 34 weeks + 0 days | 3 | 3296 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.29, 3.67] |
| 8.3 Neonatal death ‐ gestational age at trial engry Show forest plot | 22 | 7146 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.57, 0.79] |
| Analysis 8.3  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry | ||||
| 8.3.1 Less than or equal to 35 weeks + 0 days | 20 | 3855 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.57, 0.79] |
| 8.3.2 Greater than or equal to 34 weeks + 0 days | 3 | 3291 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.22, 3.07] |
| 8.4 Fetal death ‐ gestational age at trial entry Show forest plot | 15 | 6687 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.72, 1.27] |
| Analysis 8.4  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry | ||||
| 8.4.1 Less than or equal to 35 weeks + 0 days | 13 | 3391 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.71, 1.25] |
| 8.4.2 Greater than or equal to 34 weeks + 0 days | 3 | 3296 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.62 [0.28, 9.37] |
| 8.5 RDS‐ gestational age at trial entry Show forest plot | 28 | 7722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.66 [0.60, 0.73] |
| Analysis 8.5  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry | ||||
| 8.5.1 Less than or equal to 35 weeks + 0 days | 23 | 3939 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.65 [0.58, 0.73] |
| 8.5.2 Greater than or equal to 34 weeks + 0 days | 6 | 3783 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.56, 0.91] |
| 8.6 IVH ‐ gestational age at trial entry Show forest plot | 16 | 6051 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.44, 0.70] |
| Analysis 8.6  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry | ||||
| 8.6.1 Less than or equal to 35 weeks + 0 days | 13 | 2639 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.54 [0.42, 0.68] |
| 8.6.2 Greater than or equal to 34 weeks + 0 days | 4 | 3412 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 8.7 Birthweight ‐ gestational age at trial entry Show forest plot | 16 | 6140 | Mean Difference (IV, Fixed, 95% CI) | ‐17.45 [‐39.76, 4.86] |
| Analysis 8.7  Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry | ||||
| 8.7.1 Less than or equal to 35 weeks + 0 days | 11 | 2352 | Mean Difference (IV, Fixed, 95% CI) | ‐17.89 [‐63.14, 27.36] |
| 8.7.2 Greater than or equal to 34 weeks + 0 days | 6 | 3788 | Mean Difference (IV, Fixed, 95% CI) | ‐17.31 [‐42.96, 8.34] |
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 Chorioamnionitis
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.4 Perinatal deaths
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.5 Neonatal deaths
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.6 Fetal deaths
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Respiratory distress syndrome
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.10 Intraventricular haemorrhage
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Mean birthweight (g)
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.25 Need for mechanical ventilation/CPAP
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.30 Apgar < 7 at 5 minutes
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Maternal death
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Chorioamnionitis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Endometritis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Perinatal deaths
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Neonatal deaths
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Fetal deaths
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Respiratory distress syndrome
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Moderate/severe respiratory distress syndrome
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Chronic lung disease
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Intraventricular haemorrhage
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Mean birthweight (g)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental delay in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Fever in women after trial entry requiring the use of antibiotics
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Intrapartum fever in woman requiring the use of antibiotics
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Side effects of therapy in women
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Admission into adult intensive care unit
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Hypertension
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Postnatal fever in woman
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Necrotising enterocolitis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Systemic infection in the first 48 hours of life
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Proven infection while in the neonatal intensive care unit
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Need for mechanical ventilation/CPAP
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean duration of mechanical ventilation/CPAP (days)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Mean duration of oxygen supplementation (days)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Surfactant use
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Air leak syndrome
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Apgar < 7 at 5 minutes
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 31: Mean interval between trial entry and birth (days)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 32: Small‐for‐gestational age
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Mean infant HPA axis function (cortisol)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Admission to neonatal intensive care unit
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 35: Developmental delay in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Cerebral palsy in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Mean childhood weight (kg)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Mean childhood height (cm)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Mean childhood head circumference (cm)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean childhood VC (% predicted)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood FEV1 (% predicted)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood FEV1/VC
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood systolic blood pressure (mmHg)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Visual impairment in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Hearing impairment in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Intellectual impairment in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Behavioural/learning difficulties in childhood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult insulin (log values)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult glucose (mmol/L)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult weight (kg)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Mean adult height (cm)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult head circumference (cm)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult skinfold thickness (log values)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult systolic blood pressure (mmHg)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean cholesterol in adulthood (mmol/L)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Mean age at puberty (years)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Educational achievement by adulthood (university or polytechnic education)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 59: Visual impairment in adulthood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Hearing impairment in adulthood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Intellectual impairment in adulthood
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 62: Mean adult FVC (% predicted)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 63: Mean adult FEV1 (% predicted)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 64: Mean adult FEV1/FVC
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 65: Mean adult PEF
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 66: Mean adult F50
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 67: Mean adult F25
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 68: Mean adult FEF 25%‐75%
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 69: FEV1/FVC < 70%
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 70: Asthma diagnosed by Doctor in lifetime
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 71: Wheezing in last 12 months
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 72: Current Asthma
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 73: Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 74: Spontaneous pneumothorax
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 75: Shortness of breath at anytime in the last 12 months
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 76: Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 77: Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 78: Mean adult total body BMC (grams) bone mineral content
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 79: Mean adult total body aBMD (g/cm3) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 80: Mean adult femoral neck aBMD (g/cm2) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 81: Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 82: Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 83: Mean total proximal femur aBMD (g/cm2) areal bone mineral density
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 84: Mean length of antenatal hospitalisation (days)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 85: Mean length of postnatal hospitalisation (days)
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 86: Mean length of neonatal hospitalisation (days)
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Chorioamnionitis ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Perinatal death ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Neonatal death ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Fetal death ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Respiratory distress syndrome ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6: IVH ‐ single or multiple pregnancy
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7: Birthweight ‐ single or multiple pregnancy
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Chorioamnionitis ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Endometritis ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Perinatal death ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: Neonatal deaths ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: Fetal death ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: RDS ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: IVH ‐ intact or ruptured membranes
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Birthweight ‐ intact or ruptured membranes
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: RDS
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Perinatal deaths
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Neonatal deaths
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Chorioamnionitis ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Endometritis ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Perinatal death ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Neonatal deaths by steroid type
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Fetal death ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Respiratory distress syndrome ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Moderate/severe respiratory distress syndrome ‐ type of steroid
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Chronic lung disease ‐ type of steroid
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Chorioamnionitis ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Endometritis ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Perinatal deaths ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Neonatal deaths decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: Fetal death ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: RDS ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: IVH ‐ decade of trial
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Birthweight ‐ decade of trial
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Chorioamnionitis ‐ Protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Endometritis ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Perinatal death ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Neonatal death ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Fetal death ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: RDS ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: IVH‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Birthweight ‐ protocol with weekly repeats
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Moderate/severe respiratory distress syndrome
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Chorioamnionitis ‐ gestational age at trial entry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Perinatal death ‐ gestational age at trial entry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Neonatal death ‐ gestational age at trial engry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Fetal death ‐ gestational age at trial entry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: RDS‐ gestational age at trial entry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: IVH ‐ gestational age at trial entry
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Birthweight ‐ gestational age at trial entry
| Corticosteroids versus placebo or no treatment | ||||||
| Patient or population: pregnant women at high risk of preterm birth receiving a corticosteroid or placebo/no treatment; women with singleton and multiple pregnancy and intact and ruptured membranes | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo or no treatment | Risk with corticosteroids | |||||
| Maternal death | Study population | RR 0.98 | 3392 | ⊕⊕⊕⊝ | RR based on 2 deaths in a single trial (1 death in each group). Four trials reported zero events | |
| 1 per 1000 | 1 per 1000 | |||||
| Chorioamnionitis | Study population | RR 0.83 | 5546 | ⊕⊕⊕⊝ | ||
| 48 per 1000 | 40 per 1000 | |||||
| Endometritis (infections) | Study population | RR 1.20 | 4030 | ⊕⊕⊕⊝ | 7 of 10 trials reported endometritis; the remaining trials report 'infections' | |
| 33 per 1000 | 39 per 1000 | |||||
| Perinatal deaths | Study population | average RR 0.72 | 6729 | ⊕⊕⊕ | ||
| 102 per 1000 | 73 per 1000 | |||||
| Respiratory distress syndrome | Study population | average RR 0.66 | 7764 | ⊕⊕⊕ | ||
| 176 per 1000 | 116 per 1000 | |||||
| Intraventricular haemorrhage | Study population | average RR 0.55 | 6093 | ⊕⊕⊕ | ||
| 51 per 1000 | 28 per 1000 | |||||
| Mean birthweight (grams) (less is worse) | Absolute risks not calculated | The mean birthweight was 18.47g less (40.83g less to 3.90g more) | 6182 | ⊕⊕⊕ | ||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Few events and wide confidence interval led to a downgrade for imprecision (‐1). Because maternal death is a rare event and the total population is over 3000 women, we have opted for (‐1) rather than (‐2). | ||||||
| Trial | Year | Minimum (weeks+days) | Maximum (weeks+days) |
| 1999 | 28+0 | 34+6 | |
| 2015 | 34+0 | 36+6 | |
| 2010 | 34+0 | 36+6 | |
| 1976 | Not reported | 36+6 | |
| 1991 | 24+0 | 34+6 | |
| 1994 | 28+0 | 30+6 | |
| 1981 | 26+0 | 37+0 | |
| 1999 | 28+0 | 34+6 | |
| 1980 | 24+0 | 34+6 | |
| 2002 | 26+0 | 34+6 | |
| 1989 | Not reported | 34+6 | |
| 1992 | 24+0 | 27+6 | |
| 1979 | Not reported | 33+6 | |
| 2016 | 34+0 | 36+6 | |
| 1994 | 24+0 | 31+6 | |
| (no outcome data) | 2012 | 34+0 | 37+0 |
| 1996 | 24+0 | 34+6 | |
| 1972 | 24+0 | 36+6 | |
| 1989 | 27+0 | 35+0 | |
| 2010 | 35+0 | 36+6 | |
| 1989 | 26+0 | 34+6 | |
| 1985 | 28+0 | 34+6 | |
| 1988 | 25+0 | 32+6 | |
| 2011 | 34+0 | 36+6 | |
| 2001 | 27+0 | 34+6 | |
| 1980 | 26+0 | 32+6 | |
| 2010 | 34+0 | 36+6 | |
| 1996 | 24+0 | 29+6 | |
| 1979 | Not reported | 33+6 | |
| 1980 | 28+0 | 35+6 |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Maternal death Show forest plot | 5 | 3392 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.06, 15.50] |
| 1.2 Chorioamnionitis Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| 1.3 Endometritis Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.20 [0.87, 1.63] |
| 1.4 Perinatal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| 1.5 Neonatal deaths Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 1.6 Fetal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 1.7 Respiratory distress syndrome Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.56, 0.77] |
| 1.8 Moderate/severe respiratory distress syndrome Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| 1.9 Chronic lung disease Show forest plot | 6 | 818 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.42, 1.79] |
| 1.10 Intraventricular haemorrhage Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.40, 0.76] |
| 1.11 Mean birthweight (g) Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| 1.12 Death in childhood Show forest plot | 4 | 1010 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.36, 1.27] |
| 1.13 Neurodevelopmental delay in childhood Show forest plot | 1 | 82 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.14, 2.98] |
| 1.14 Death into adulthood Show forest plot | 1 | 988 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.56, 1.81] |
| 1.15 Fever in women after trial entry requiring the use of antibiotics Show forest plot | 4 | 481 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.43, 2.06] |
| 1.16 Intrapartum fever in woman requiring the use of antibiotics Show forest plot | 2 | 319 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.09, 4.89] |
| 1.17 Side effects of therapy in women Show forest plot | 6 | 3572 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.82] |
| 1.18 Admission into adult intensive care unit Show forest plot | 2 | 319 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.74 [0.26, 2.05] |
| 1.19 Hypertension Show forest plot | 1 | 220 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.36, 2.76] |
| 1.20 Postnatal fever in woman Show forest plot | 5 | 1323 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.64, 1.33] |
| 1.21 Glucose intolerance Show forest plot | 1 | 123 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.71 [1.14, 6.46] |
| 1.22 Necrotising enterocolitis Show forest plot | 10 | 4702 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.32, 0.78] |
| 1.23 Systemic infection in the first 48 hours of life Show forest plot | 8 | 1753 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.41, 0.88] |
| 1.24 Proven infection while in the neonatal intensive care unit Show forest plot | 13 | 5707 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.55, 1.08] |
| 1.25 Need for mechanical ventilation/CPAP Show forest plot | 9 | 1368 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.56, 0.84] |
| 1.26 Mean duration of mechanical ventilation/CPAP (days) Show forest plot | 3 | 471 | Mean Difference (IV, Random, 95% CI) | ‐1.91 [‐4.59, 0.76] |
| 1.27 Mean duration of oxygen supplementation (days) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.28 Surfactant use Show forest plot | 5 | 3556 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.51, 0.90] |
| 1.29 Air leak syndrome Show forest plot | 2 | 2965 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.76 [0.32, 1.80] |
| 1.30 Apgar < 7 at 5 minutes Show forest plot | 10 | 2419 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.67, 0.98] |
| 1.31 Mean interval between trial entry and birth (days) Show forest plot | 3 | 1513 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [‐1.86, 2.32] |
| 1.32 Small‐for‐gestational age Show forest plot | 5 | 3478 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.96, 1.28] |
| 1.33 Mean infant HPA axis function (cortisol) Show forest plot | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 3.94 [‐3.12, 11.00] |
| 1.33.1 In babies born < 24 hours after 1st dose | 1 | 6 | Mean Difference (IV, Fixed, 95% CI) | 9.00 [‐11.93, 29.93] |
| 1.33.2 In babies born 24‐48 hours after 1st dose | 1 | 10 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐8.68, 8.68] |
| 1.33.3 In babies born > 48 hours after 1st dose | 1 | 11 | Mean Difference (IV, Fixed, 95% CI) | 13.00 [‐1.90, 27.90] |
| 1.34 Admission to neonatal intensive care unit Show forest plot | 7 | 3803 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.84, 0.97] |
| 1.35 Developmental delay in childhood Show forest plot | 2 | 518 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.49 [0.24, 1.00] |
| 1.36 Cerebral palsy in childhood Show forest plot | 5 | 904 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.34, 1.03] |
| 1.37 Mean childhood weight (kg) Show forest plot | 2 | 333 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.39, 1.00] |
| 1.37.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐0.32, 1.12] |
| 1.37.2 Schutte (females) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐2.40 [‐6.55, 1.75] |
| 1.37.3 Schutte (males) | 1 | 44 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐3.88, 3.68] |
| 1.38 Mean childhood height (cm) Show forest plot | 2 | 334 | Mean Difference (IV, Fixed, 95% CI) | 1.02 [‐0.26, 2.29] |
| 1.38.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 1.00 [‐0.39, 2.39] |
| 1.38.2 Schutte (females) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | 1.70 [‐3.08, 6.48] |
| 1.38.3 Schutte (males) | 1 | 45 | Mean Difference (IV, Fixed, 95% CI) | 0.60 [‐3.79, 4.99] |
| 1.39 Mean childhood head circumference (cm) Show forest plot | 2 | 328 | Mean Difference (IV, Fixed, 95% CI) | 0.27 [‐0.08, 0.63] |
| 1.39.1 Liggins | 1 | 250 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐0.11, 0.71] |
| 1.39.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐1.05, 0.85] |
| 1.39.3 Schutte (males) | 1 | 42 | Mean Difference (IV, Fixed, 95% CI) | 0.60 [‐0.51, 1.71] |
| 1.40 Mean childhood VC (% predicted) Show forest plot | 2 | 150 | Mean Difference (IV, Fixed, 95% CI) | ‐1.68 [‐5.12, 1.75] |
| 1.40.1 Liggins | 1 | 75 | Mean Difference (IV, Fixed, 95% CI) | 0.70 [‐5.12, 6.52] |
| 1.40.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐2.60 [‐8.65, 3.45] |
| 1.40.3 Schutte (males) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐3.30 [‐9.27, 2.67] |
| 1.41 Mean childhood FEV1 (% predicted) Show forest plot | 1 | 75 | Mean Difference (IV, Fixed, 95% CI) | ‐4.73 [‐10.13, 0.67] |
| 1.41.1 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐2.50 [‐11.24, 6.24] |
| 1.41.2 Schutte (males) | 1 | 39 | Mean Difference (IV, Fixed, 95% CI) | ‐6.10 [‐12.96, 0.76] |
| 1.42 Mean childhood FEV1/VC Show forest plot | 2 | 150 | Mean Difference (IV, Random, 95% CI) | ‐0.94 [‐3.63, 1.76] |
| 1.42.1 Liggins | 1 | 75 | Mean Difference (IV, Random, 95% CI) | 1.00 [‐2.57, 4.57] |
| 1.42.2 Schutte (females) | 1 | 36 | Mean Difference (IV, Random, 95% CI) | 0.00 [‐5.56, 5.56] |
| 1.42.3 Schutte (males) | 1 | 39 | Mean Difference (IV, Random, 95% CI) | ‐3.00 [‐6.14, 0.14] |
| 1.43 Mean childhood systolic blood pressure (mmHg) Show forest plot | 1 | 223 | Mean Difference (IV, Fixed, 95% CI) | ‐1.60 [‐4.06, 0.86] |
| 1.44 Visual impairment in childhood Show forest plot | 2 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.24, 1.23] |
| 1.45 Hearing impairment in childhood Show forest plot | 2 | 166 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.04, 9.87] |
| 1.46 Intellectual impairment in childhood Show forest plot | 3 | 778 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.44, 1.69] |
| 1.47 Behavioural/learning difficulties in childhood Show forest plot | 1 | 90 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.35, 2.09] |
| 1.48 Mean adult insulin (log values) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.48.1 Fasting | 1 | 435 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [‐0.03, 0.19] |
| 1.48.2 30 minutes following a 75 g oral glucose tolerance test | 1 | 412 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [0.04, 0.28] |
| 1.48.3 120 minutes following a 75 g oral glucose tolerance test | 1 | 428 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐0.27, 0.07] |
| 1.49 Mean adult glucose (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.49.1 Fasting | 1 | 432 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.09, 0.11] |
| 1.49.2 30 minutes following a 75 g oral glucose tolerance test | 1 | 413 | Mean Difference (IV, Fixed, 95% CI) | 0.19 [‐0.14, 0.52] |
| 1.49.3 120 minutes following a 75 g oral glucose tolerance test | 1 | 410 | Mean Difference (IV, Fixed, 95% CI) | ‐0.27 [‐0.52, ‐0.02] |
| 1.50 Mean adult weight (kg) Show forest plot | 2 | 538 | Mean Difference (IV, Random, 95% CI) | ‐0.83 [‐6.41, 4.76] |
| 1.50.1 Schutte (females) | 1 | 37 | Mean Difference (IV, Random, 95% CI) | ‐6.00 [‐12.93, 0.93] |
| 1.50.2 Schutte (males) | 1 | 43 | Mean Difference (IV, Random, 95% CI) | ‐1.00 [‐9.91, 7.91] |
| 1.50.3 Liggins | 1 | 458 | Mean Difference (IV, Random, 95% CI) | 2.57 [‐0.72, 5.86] |
| 1.51 Mean adult height (cm) Show forest plot | 2 | 537 | Mean Difference (IV, Fixed, 95% CI) | 0.91 [‐0.28, 2.10] |
| 1.51.1 Schutte (females) | 1 | 36 | Mean Difference (IV, Fixed, 95% CI) | ‐1.00 [‐5.37, 3.37] |
| 1.51.2 Schutte (males) | 1 | 43 | Mean Difference (IV, Fixed, 95% CI) | 3.00 [‐2.30, 8.30] |
| 1.51.3 Liggins (females) | 1 | 234 | Mean Difference (IV, Fixed, 95% CI) | 1.17 [‐0.65, 2.99] |
| 1.51.4 Liggins (males) | 1 | 224 | Mean Difference (IV, Fixed, 95% CI) | 0.75 [‐1.03, 2.53] |
| 1.52 Mean adult head circumference (cm) Show forest plot | 2 | 537 | Mean Difference (IV, Fixed, 95% CI) | 0.03 [‐0.33, 0.38] |
| 1.52.1 Schutte (females) | 1 | 37 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐1.03, 1.03] |
| 1.52.2 Schutte (males) | 1 | 42 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐1.37, 0.97] |
| 1.52.3 Liggins | 1 | 458 | Mean Difference (IV, Fixed, 95% CI) | 0.06 [‐0.34, 0.46] |
| 1.53 Mean adult skinfold thickness (log values) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.53.1 Triceps | 1 | 456 | Mean Difference (IV, Fixed, 95% CI) | ‐0.02 [‐0.11, 0.07] |
| 1.53.2 Biceps | 1 | 456 | Mean Difference (IV, Fixed, 95% CI) | ‐0.01 [‐0.11, 0.09] |
| 1.53.3 Subscapular | 1 | 441 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.08, 0.10] |
| 1.53.4 Suprailiac | 1 | 452 | Mean Difference (IV, Fixed, 95% CI) | ‐0.01 [‐0.12, 0.10] |
| 1.54 Mean adult systolic blood pressure (mmHg) Show forest plot | 2 | 545 | Mean Difference (IV, Random, 95% CI) | ‐1.53 [‐4.50, 1.44] |
| 1.54.1 Schutte (females) | 1 | 38 | Mean Difference (IV, Random, 95% CI) | ‐4.00 [‐9.12, 1.12] |
| 1.54.2 Schutte (males) | 1 | 52 | Mean Difference (IV, Random, 95% CI) | ‐3.00 [‐7.17, 1.17] |
| 1.54.3 Liggins | 1 | 455 | Mean Difference (IV, Random, 95% CI) | 0.55 [‐1.88, 2.98] |
| 1.55 Mean adult HPA axis function (mean log fasting cortisol) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.56 Mean cholesterol in adulthood (mmol/L) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.57 Mean age at puberty (years) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.57.1 Schutte (females) | 1 | 38 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.94, 0.94] |
| 1.58 Educational achievement by adulthood (university or polytechnic education) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.59 Visual impairment in adulthood Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.60 Hearing impairment in adulthood Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.61 Intellectual impairment in adulthood Show forest plot | 2 | 273 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.24 [0.01, 4.95] |
| 1.62 Mean adult FVC (% predicted) Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | ‐0.70 [‐3.16, 1.76] |
| 1.63 Mean adult FEV1 (% predicted) Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐2.31, 3.11] |
| 1.64 Mean adult FEV1/FVC Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.01, 0.03] |
| 1.65 Mean adult PEF Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 2.20 [‐0.77, 5.17] |
| 1.66 Mean adult F50 Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 3.00 [‐1.57, 7.57] |
| 1.67 Mean adult F25 Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 0.40 [‐3.82, 4.62] |
| 1.68 Mean adult FEF 25%‐75% Show forest plot | 1 | 383 | Mean Difference (IV, Fixed, 95% CI) | 2.20 [‐2.10, 6.50] |
| 1.69 FEV1/FVC < 70% Show forest plot | 1 | 383 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.49, 1.57] |
| 1.70 Asthma diagnosed by Doctor in lifetime Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 1.71 Wheezing in last 12 months Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.06 [0.84, 1.35] |
| 1.72 Current Asthma Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.74, 1.48] |
| 1.73 Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis) Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.33 [0.69, 2.59] |
| 1.74 Spontaneous pneumothorax Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.07, 17.66] |
| 1.75 Shortness of breath at anytime in the last 12 months Show forest plot | 1 | 534 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.80, 1.31] |
| 1.76 Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.04, 0.04] |
| 1.77 Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.01, 0.01] |
| 1.78 Mean adult total body BMC (grams) bone mineral content Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 18.00 [‐151.30, 187.30] |
| 1.79 Mean adult total body aBMD (g/cm3) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.03, 0.03] |
| 1.80 Mean adult femoral neck aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.03, 0.07] |
| 1.81 Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.02, 0.06] |
| 1.82 Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.04, 0.06] |
| 1.83 Mean total proximal femur aBMD (g/cm2) areal bone mineral density Show forest plot | 1 | 174 | Mean Difference (IV, Fixed, 95% CI) | 0.02 [‐0.03, 0.07] |
| 1.84 Mean length of antenatal hospitalisation (days) Show forest plot | 1 | 218 | Mean Difference (IV, Fixed, 95% CI) | 0.50 [‐1.40, 2.40] |
| 1.85 Mean length of postnatal hospitalisation (days) Show forest plot | 1 | 218 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐1.72, 1.72] |
| 1.86 Mean length of neonatal hospitalisation (days) Show forest plot | 5 | 788 | Mean Difference (IV, Fixed, 95% CI) | 0.18 [‐0.51, 0.87] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Chorioamnionitis ‐ single or multiple pregnancy Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| 2.1.1 In women delivering singleton pregnancies | 7 | 4682 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.56, 1.01] |
| 2.1.2 In women delivering multiple pregnancies | 1 | 74 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.42 [0.04, 4.49] |
| 2.1.3 Mixed population | 8 | 790 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.70, 1.57] |
| 2.2 Perinatal death ‐ single or multiple pregnancy Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.59, 0.89] |
| 2.2.1 In babies born from singleton pregnancies | 6 | 5182 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.54, 1.05] |
| 2.2.2 In babies born from multiple pregnancies | 2 | 252 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.37, 1.47] |
| 2.2.3 Mixed population | 9 | 1295 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.49, 0.94] |
| 2.3 Neonatal death ‐ single or multiple pregnancy Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 2.3.1 In babies born from singleton pregnancies | 9 | 5335 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.61, 0.92] |
| 2.3.2 In babies born from multiple pregnancies | 2 | 236 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.79 [0.39, 1.61] |
| 2.3.3 Mixed population | 13 | 1617 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.46, 0.78] |
| 2.4 Fetal death ‐ single or multiple pregnancy Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.97 [0.73, 1.29] |
| 2.4.1 In babies born from singleton pregnancies | 6 | 5182 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.04 [0.75, 1.45] |
| 2.4.2 In babies born from multiple pregnancies | 2 | 252 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.53 [0.20, 1.40] |
| 2.4.3 Mixed population | 9 | 1295 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.99 [0.50, 1.99] |
| 2.5 Respiratory distress syndrome ‐ single or multiple pregnancy Show forest plot | 28 | 7762 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.59, 0.78] |
| 2.5.1 In babies born from singleton pregnancies | 15 | 6081 | Risk Ratio (M‐H, Random, 95% CI) | 0.62 [0.50, 0.77] |
| 2.5.2 In babies born from multiple pregnancies | 4 | 320 | Risk Ratio (M‐H, Random, 95% CI) | 0.90 [0.67, 1.22] |
| 2.5.3 Mixed population | 13 | 1361 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.53, 0.89] |
| 2.6 IVH ‐ single or multiple pregnancy Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| 2.6.1 In babies born from singleton pregnancies | 8 | 4782 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.52 [0.36, 0.75] |
| 2.6.2 In babies born from multiple pregnancies | 1 | 137 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.39 [0.07, 2.06] |
| 2.6.3 Mixed population | 8 | 1174 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.60 [0.44, 0.81] |
| 2.7 Birthweight ‐ single or multiple pregnancy Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐17.61 [‐39.95, 4.74] |
| 2.7.1 In babies born from singleton pregnancy | 9 | 4948 | Mean Difference (IV, Fixed, 95% CI) | ‐24.12 [‐48.27, 0.03] |
| 2.7.2 In babies born from multiple pregnancies | 1 | 150 | Mean Difference (IV, Fixed, 95% CI) | 82.36 [‐146.23, 310.95] |
| 2.7.3 Mixed population | 7 | 1084 | Mean Difference (IV, Fixed, 95% CI) | 16.77 [‐44.16, 77.69] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Chorioamnionitis ‐ intact or ruptured membranes Show forest plot | 15 | 5517 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.85 [0.67, 1.07] |
| 3.1.1 In women with intact membranes at 1st dose | 5 | 1437 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.50, 1.40] |
| 3.1.2 In women with ruptured membranes at 1st dose | 7 | 959 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.69, 1.40] |
| 3.1.3 Not reported or mixed population | 4 | 3121 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.47, 1.06] |
| 3.2 Endometritis ‐ intact or ruptured membranes Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.80, 1.80] |
| 3.2.1 In women with intact membranes at 1st dose | 2 | 289 | Risk Ratio (M‐H, Random, 95% CI) | 1.21 [0.37, 4.01] |
| 3.2.2 In women with ruptured membranes at 1st dose | 4 | 477 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.35, 2.97] |
| 3.2.3 Not reported or mixed population | 5 | 3264 | Risk Ratio (M‐H, Random, 95% CI) | 1.31 [0.81, 2.13] |
| 3.3 Perinatal death ‐ intact or ruptured membranes Show forest plot | 15 | 6700 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.60, 0.90] |
| 3.3.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1332 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.70, 1.08] |
| 3.3.2 In babies born from pregnancies with ruptured membranes at 1st dose | 4 | 733 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.39, 0.90] |
| 3.3.3 Not reported or mixed population | 8 | 4635 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.49, 1.03] |
| 3.4 Neonatal deaths ‐ intact or ruptured membranes Show forest plot | 22 | 7163 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 3.4.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1236 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.58, 1.03] |
| 3.4.2 In babies born from pregnancies with ruptured membranes at 1st dose | 8 | 1024 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.46, 0.83] |
| 3.4.3 Not reported or mixed population | 11 | 4903 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.53, 0.88] |
| 3.5 Fetal death ‐ intact or ruptured membranes Show forest plot | 15 | 6634 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.71, 1.26] |
| 3.5.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1332 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.09 [0.73, 1.64] |
| 3.5.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 790 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.46, 1.61] |
| 3.5.3 Not reported or mixed population | 7 | 4512 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.44, 1.35] |
| 3.6 RDS ‐ intact or ruptured membranes Show forest plot | 28 | 7738 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.56, 0.76] |
| 3.6.1 In babies born from pregnancies with intact membranes at 1st dose | 6 | 1721 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.50, 0.80] |
| 3.6.2 In babies born from pregnancies with ruptured membranes at 1st dose | 12 | 1129 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.55, 0.90] |
| 3.6.3 Not reported or mixed population | 14 | 4888 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.46, 0.81] |
| 3.7 IVH ‐ intact or ruptured membranes Show forest plot | 15 | 5868 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| 3.7.1 In babies born from pregnancies with intact membranes at 1st dose | 5 | 1394 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.35, 0.72] |
| 3.7.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 895 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.47 [0.28, 0.79] |
| 3.7.3 Not reported or mixed population | 6 | 3579 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.49, 1.07] |
| 3.8 Birthweight ‐ intact or ruptured membranes Show forest plot | 16 | 6153 | Mean Difference (IV, Fixed, 95% CI) | ‐19.52 [‐41.81, 2.78] |
| 3.8.1 In babies born from pregnancies with intact membranes at 1st dose | 4 | 1301 | Mean Difference (IV, Fixed, 95% CI) | ‐30.27 [‐100.43, 39.89] |
| 3.8.2 In babies born from pregnancies with ruptured membranes at 1st dose | 5 | 835 | Mean Difference (IV, Fixed, 95% CI) | ‐49.72 [‐113.91, 14.46] |
| 3.8.3 Not reported or mixed population | 8 | 4017 | Mean Difference (IV, Fixed, 95% CI) | ‐13.44 [‐38.71, 11.83] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 RDS Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| 4.1.1 Hypertension syndrome | 5 | 382 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.35, 0.72] |
| 4.1.2 No hypertension syndrome or hypertension syndromes excluded | 9 | 2660 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.58 [0.47, 0.71] |
| 4.1.3 Hypertension not reported separately | 18 | 4722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.75 [0.66, 0.85] |
| 4.2 Perinatal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.60, 0.92] |
| 4.2.1 Hypertension syndrome | 2 | 313 | Risk Ratio (M‐H, Random, 95% CI) | 0.94 [0.42, 2.10] |
| 4.2.2 No hypertension syndrome or hypertension syndromes excluded | 3 | 1394 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.39, 1.29] |
| 4.2.3 Hypertension not reported separately | 11 | 5022 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.52, 0.93] |
| 4.3 Fetal deaths Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 4.3.1 Women with hypertension syndrome | 3 | 331 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.73 [0.91, 3.28] |
| 4.3.2 No hypertension syndrome or hypertension syndromes excluded | 4 | 1644 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.73 [0.49, 1.08] |
| 4.3.3 Hypertension not reported separately | 10 | 4754 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.15 [0.67, 1.98] |
| 4.4 Neonatal deaths Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 4.4.1 Hypertension syndrome | 2 | 278 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.29, 0.87] |
| 4.4.2 No hypertension syndrome or hypertension syndromes excluded | 3 | 1306 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.61, 1.09] |
| 4.4.3 Hypertension not reported separately | 18 | 5604 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.66 [0.54, 0.82] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Chorioamnionitis ‐ type of steroid Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| 5.1.1 In women treated with dexamethasone | 5 | 769 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.35 [0.89, 2.05] |
| 5.1.2 In women treated with betamethasone | 10 | 4777 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.50, 0.90] |
| 5.2 Endometritis ‐ type of steroid Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.81, 1.80] |
| 5.2.1 In women treated with dexamethasone | 4 | 536 | Risk Ratio (M‐H, Random, 95% CI) | 1.71 [0.86, 3.43] |
| 5.2.2 In women treated with betamethasone | 6 | 3494 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.63, 1.45] |
| 5.3 Perinatal death ‐ type of steroid Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| 5.3.1 In babies treated with dexamethasone | 5 | 1420 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.46, 1.11] |
| 5.3.2 In babies treated with betamethasone | 10 | 5309 | Risk Ratio (M‐H, Random, 95% CI) | 0.73 [0.56, 0.94] |
| 5.4 Neonatal deaths by steroid type Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 5.4.1 In babies treated with dexamethasone | 6 | 1468 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.55, 0.94] |
| 5.4.2 In babies treated with betamethasone | 16 | 5720 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.55, 0.83] |
| 5.5 Fetal death ‐ type of steroid Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 5.5.1 In babies treated with dexamethasone | 5 | 1420 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.88 [0.48, 1.60] |
| 5.5.2 In babies treated with betamethasone | 10 | 5309 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.73, 1.39] |
| 5.6 Respiratory distress syndrome ‐ type of steroid Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.56, 0.77] |
| 5.6.1 In babies treated with dexamethasone | 7 | 1651 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.61, 0.98] |
| 5.6.2 In babies treated with betamethasone | 20 | 6095 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.50, 0.73] |
| 5.6.3 Steroid type not reported | 1 | 18 | Risk Ratio (M‐H, Random, 95% CI) | 1.62 [0.08, 34.66] |
| 5.7 IVH ‐ type of steroid Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.40, 0.76] |
| 5.7.1 In babies treated with dexamethasone | 6 | 897 | Risk Ratio (M‐H, Random, 95% CI) | 0.48 [0.18, 1.26] |
| 5.7.2 In babies treated with betamethasone | 10 | 5196 | Risk Ratio (M‐H, Random, 95% CI) | 0.53 [0.40, 0.72] |
| 5.8 Birthweight ‐ type of steroid Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| 5.8.1 In babies treated with dexamethasone | 4 | 686 | Mean Difference (IV, Fixed, 95% CI) | ‐17.04 [‐75.48, 41.41] |
| 5.8.2 In babies treated with betamethasone | 12 | 5496 | Mean Difference (IV, Fixed, 95% CI) | ‐18.71 [‐42.92, 5.50] |
| 5.9 Moderate/severe respiratory distress syndrome ‐ type of steroid Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| 5.9.1 Dexamethasone | 2 | 219 | Risk Ratio (M‐H, Random, 95% CI) | 0.82 [0.46, 1.44] |
| 5.9.2 Betamethasone | 4 | 1467 | Risk Ratio (M‐H, Random, 95% CI) | 0.49 [0.27, 0.90] |
| 5.10 Chronic lung disease ‐ type of steroid Show forest plot | 6 | 818 | Risk Ratio (M‐H, Random, 95% CI) | 0.86 [0.42, 1.79] |
| 5.10.1 Dexamethasone | 2 | 219 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.72, 1.90] |
| 5.10.2 Betamethasone | 4 | 599 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.26, 2.28] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Chorioamnionitis ‐ decade of trial Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| 6.1.1 In women from trials conducted in 1970s | 2 | 1237 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.74 [0.46, 1.17] |
| 6.1.2 In women from trials conducted in 1980s | 3 | 276 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.25, 1.01] |
| 6.1.3 In women from trials conducted in 1990s | 6 | 755 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.18 [0.80, 1.74] |
| 6.1.4 in women from trials conducted in the 2000's | 2 | 257 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.02 [0.59, 6.95] |
| 6.1.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.35, 1.07] |
| 6.2 Endometritis ‐ decade of trial Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.20 [0.87, 1.63] |
| 6.2.1 In women from trials conducted in 1970s | 2 | 219 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.86 [0.81, 4.27] |
| 6.2.2 In women from trials conducted in 1980s | 1 | 71 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.30 [0.88, 6.06] |
| 6.2.3 In women from trials conducted in 1990s | 4 | 574 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.53, 1.44] |
| 6.2.4 In women from trials conducted in the 2000's | 3 | 3166 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.18 [0.69, 2.01] |
| 6.3 Perinatal deaths ‐ decade of trial Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| 6.3.1 In babies from trials conducted in 1970s | 6 | 1994 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.50, 1.00] |
| 6.3.2 In babies from trials conducted in 1980s | 3 | 879 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.74, 1.42] |
| 6.3.3 In babies from trials conducted in 1990s | 3 | 615 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.43, 0.93] |
| 6.3.4 in babies from trials conducted in 2000's | 2 | 414 | Risk Ratio (M‐H, Random, 95% CI) | 0.47 [0.31, 0.70] |
| 6.3.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Random, 95% CI) | 4.91 [0.24, 102.09] |
| 6.4 Neonatal deaths decade of trial Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 6.4.1 In babies from trials conducted in 1970s | 7 | 1968 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.56, 0.92] |
| 6.4.2 In babies from trials conducted in 1980s | 6 | 1096 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.70, 1.37] |
| 6.4.3 In babies from trials conducted in 1990s | 5 | 758 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.36, 0.84] |
| 6.4.4 In babies from trials conducted in 2000s | 3 | 539 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.44 [0.31, 0.64] |
| 6.4.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 6.5 Fetal death ‐ decade of trial Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 6.5.1 In babies from trials conducted in 1970s | 6 | 1994 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.95 [0.67, 1.34] |
| 6.5.2 In babies from trials conducted in 1980s | 3 | 879 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.52, 2.00] |
| 6.5.3 In babies from trials conducted in 1990s | 3 | 615 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.49, 2.36] |
| 6.5.4 In babies from trials conducted in 2000's | 2 | 414 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.19, 4.50] |
| 6.5.5 In trials conducted in 2010s | 1 | 2827 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 6.6 RDS ‐ decade of trial Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| 6.6.1 In babies from trials conducted in 1970s | 7 | 1939 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.54 [0.43, 0.69] |
| 6.6.2 In babies from trials conducted in 1980s | 7 | 1167 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.59, 0.88] |
| 6.6.3 In babies from trials conducted in 1990s | 7 | 798 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.65, 0.91] |
| 6.6.4 In babies from trials conducted in 2000s | 5 | 839 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.39 [0.26, 0.59] |
| 6.6.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.80 [0.61, 1.04] |
| 6.7 IVH ‐ decade of trial Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| 6.7.1 In babies from trials conducted in 1970s | 4 | 1646 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.29, 0.85] |
| 6.7.2 In babies from trials conducted in 1980s | 2 | 238 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.39, 0.94] |
| 6.7.3 In babies from trials conducted in 1990s | 5 | 722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.42, 0.87] |
| 6.7.4 In babies from trials conducted in 2000s | 3 | 466 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.33 [0.15, 0.73] |
| 6.7.5 In trials from 2010s | 2 | 3021 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 6.8 Birthweight ‐ decade of trial Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| 6.8.1 In babies from trials conducted in 1970s | 4 | 1739 | Mean Difference (IV, Fixed, 95% CI) | ‐9.54 [‐83.55, 64.47] |
| 6.8.2 In babies from trials conducted in 1980s | 3 | 280 | Mean Difference (IV, Fixed, 95% CI) | ‐19.60 [‐108.55, 69.35] |
| 6.8.3 In babies from trials conducted in 1990s | 4 | 569 | Mean Difference (IV, Fixed, 95% CI) | ‐33.13 [‐102.39, 36.13] |
| 6.8.4 In babies from trials conducted in 2000s | 3 | 573 | Mean Difference (IV, Fixed, 95% CI) | ‐20.77 [‐61.95, 20.41] |
| 6.8.5 In trials in 2010s | 2 | 3021 | Mean Difference (IV, Fixed, 95% CI) | ‐15.18 [‐48.66, 18.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Chorioamnionitis ‐ Protocol with weekly repeats Show forest plot | 15 | 5546 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.66, 1.06] |
| 7.1.1 In women treated with single courses only | 7 | 4659 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.61, 1.11] |
| 7.1.2 In women treated with courses including weekly repeats | 8 | 887 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.57, 1.25] |
| 7.2 Endometritis ‐ protocol with weekly repeats Show forest plot | 10 | 4030 | Risk Ratio (M‐H, Random, 95% CI) | 1.20 [0.81, 1.80] |
| 7.2.1 In women treated with single courses only | 5 | 3450 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.66, 1.64] |
| 7.2.2 In women treated with courses including weekly repeats | 5 | 580 | Risk Ratio (M‐H, Random, 95% CI) | 1.46 [0.72, 2.95] |
| 7.3 Perinatal death ‐ protocol with weekly repeats Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.58, 0.89] |
| 7.3.1 In babies treated with single course only | 11 | 6250 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.61, 0.99] |
| 7.3.2 In babies treated with courses including weekly repeats | 4 | 479 | Risk Ratio (M‐H, Random, 95% CI) | 0.65 [0.44, 0.97] |
| 7.4 Neonatal death ‐ protocol with weekly repeats Show forest plot | 22 | 7188 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.59, 0.81] |
| 7.4.1 In babies treated with single course only | 14 | 6266 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.78 [0.63, 0.95] |
| 7.4.2 In babies treated with courses including weekly repeats | 8 | 922 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.43, 0.72] |
| 7.5 Fetal death ‐ protocol with weekly repeats Show forest plot | 15 | 6729 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.98 [0.74, 1.30] |
| 7.5.1 In babies treated with single course only | 11 | 6250 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.92 [0.68, 1.25] |
| 7.5.2 In babies treated with courses including weekly repeats | 4 | 479 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.36 [0.64, 2.87] |
| 7.6 RDS ‐ protocol with weekly repeats Show forest plot | 28 | 7764 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.60, 0.74] |
| 7.6.1 In babies treated with single course only | 19 | 6818 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.61, 0.79] |
| 7.6.2 In babies treated with courses including weekly repeats | 9 | 946 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.61 [0.52, 0.72] |
| 7.7 IVH‐ protocol with weekly repeats Show forest plot | 16 | 6093 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.44, 0.70] |
| 7.7.1 In babies treated with single course only | 9 | 5216 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.50 [0.33, 0.76] |
| 7.7.2 In babies treated with courses including weekly repeats | 7 | 877 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.59 [0.45, 0.78] |
| 7.8 Birthweight ‐ protocol with weekly repeats Show forest plot | 16 | 6182 | Mean Difference (IV, Fixed, 95% CI) | ‐18.47 [‐40.83, 3.90] |
| 7.8.1 In babies treated with single course only | 12 | 5773 | Mean Difference (IV, Fixed, 95% CI) | ‐18.24 [‐42.12, 5.65] |
| 7.8.2 In babies treated with courses including weekly repeats | 4 | 409 | Mean Difference (IV, Fixed, 95% CI) | ‐20.10 [‐83.79, 43.60] |
| 7.9 Moderate/severe respiratory distress syndrome Show forest plot | 6 | 1686 | Risk Ratio (M‐H, Random, 95% CI) | 0.59 [0.38, 0.91] |
| 7.9.1 Single course | 3 | 1259 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.44, 0.83] |
| 7.9.2 Weekly repeats | 3 | 427 | Risk Ratio (M‐H, Random, 95% CI) | 0.41 [0.13, 1.32] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Chorioamnionitis ‐ gestational age at trial entry Show forest plot | 15 | 5506 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.82 [0.65, 1.05] |
| 8.1.1 Less than or equal to 35 weeks + 0 days | 13 | 2304 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.91 [0.70, 1.19] |
| 8.1.2 Greater than or equal to 34 weeks + 0 days | 3 | 3202 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.57 [0.33, 0.99] |
| 8.2 Perinatal death ‐ gestational age at trial entry Show forest plot | 15 | 6687 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.59, 0.88] |
| 8.2.1 Less than or equal to 35 weeks + 0 days | 13 | 3391 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.58, 0.87] |
| 8.2.2 Greater than or equal to 34 weeks + 0 days | 3 | 3296 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.29, 3.67] |
| 8.3 Neonatal death ‐ gestational age at trial engry Show forest plot | 22 | 7146 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.57, 0.79] |
| 8.3.1 Less than or equal to 35 weeks + 0 days | 20 | 3855 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.57, 0.79] |
| 8.3.2 Greater than or equal to 34 weeks + 0 days | 3 | 3291 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.22, 3.07] |
| 8.4 Fetal death ‐ gestational age at trial entry Show forest plot | 15 | 6687 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.96 [0.72, 1.27] |
| 8.4.1 Less than or equal to 35 weeks + 0 days | 13 | 3391 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.71, 1.25] |
| 8.4.2 Greater than or equal to 34 weeks + 0 days | 3 | 3296 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.62 [0.28, 9.37] |
| 8.5 RDS‐ gestational age at trial entry Show forest plot | 28 | 7722 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.66 [0.60, 0.73] |
| 8.5.1 Less than or equal to 35 weeks + 0 days | 23 | 3939 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.65 [0.58, 0.73] |
| 8.5.2 Greater than or equal to 34 weeks + 0 days | 6 | 3783 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.71 [0.56, 0.91] |
| 8.6 IVH ‐ gestational age at trial entry Show forest plot | 16 | 6051 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.55 [0.44, 0.70] |
| 8.6.1 Less than or equal to 35 weeks + 0 days | 13 | 2639 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.54 [0.42, 0.68] |
| 8.6.2 Greater than or equal to 34 weeks + 0 days | 4 | 3412 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.91 [0.24, 102.09] |
| 8.7 Birthweight ‐ gestational age at trial entry Show forest plot | 16 | 6140 | Mean Difference (IV, Fixed, 95% CI) | ‐17.45 [‐39.76, 4.86] |
| 8.7.1 Less than or equal to 35 weeks + 0 days | 11 | 2352 | Mean Difference (IV, Fixed, 95% CI) | ‐17.89 [‐63.14, 27.36] |
| 8.7.2 Greater than or equal to 34 weeks + 0 days | 6 | 3788 | Mean Difference (IV, Fixed, 95% CI) | ‐17.31 [‐42.96, 8.34] |
