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Meta-Analysis
. 2020 Dec 25;12(12):CD004454.
doi: 10.1002/14651858.CD004454.pub4.

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

Emma McGoldrick #  1 , Fiona Stewart #  2 , Roses Parker  3 , Stuart R Dalziel  4   5
Affiliations
Meta-Analysis

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

Emma McGoldrick et al. Cochrane Database Syst Rev. .

Abstract

Background: Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.

Objectives: To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies.

Selection criteria: We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review.

Data collection and analysis: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death.

Main results: We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of: - perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; 9833 infants; 14 studies; high-certainty evidence; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), - neonatal death (RR 0.78, 95% CI 0.70 to 0.87; 10,609 infants; 22 studies; high-certainty evidence; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), - respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78; 11,183 infants; studies = 26; high-certainty evidence; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75; 8475 infants; 12 studies; moderate-certainty evidence; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76; 9551 infants; 19 studies; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97; 600 children; 3 studies; moderate-certainty evidence; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89; 6244 women; 6 studies; moderate-certainty evidence; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08; 8374 women; 15 studies; moderate-certainty evidence; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58; 6764 women; 10 studies; moderate-certainty; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm.

Authors' conclusions: Evidence from this updated review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and RDS and probably reduces the risk of IVH. This evidence is robust, regardless of resource setting (high, middle or low). Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high-risk obstetric groups, and the risks and benefits in the very early or very late preterm periods. Additionally, outcomes from existing trials with follow-up into childhood and adulthood are needed in order to investigate any longer-term effects of antenatal corticosteroids. We encourage authors of previous studies to provide further information which may answer any remaining questions about the use of antenatal corticosteroids without the need for further randomised controlled trials. Individual patient data meta-analyses from published trials are likely to provide answers for most of the remaining clinical uncertainties.

Trial registration: ClinicalTrials.gov NCT01222247 NCT01084096 NCT03547791.

PubMed Disclaimer

Conflict of interest statement

Fiona Stewart: none known

Emma McGoldrick: none known

Roses Parker: none known

Stuart Dalziel reports receiving research funding, not associated with the review topic, from Cure Kids, Health Research Council, and Starship Foundation, New Zealand. Stuart Dalziel is employed by The University of Auckland and Auckland District Health Board. He is also on the board of the Advanced Paediatric Life Support New Zealand.

Figures

1
1
Applying the trustworthiness screening tool criteria
2
2
Study flow diagram.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
4
4
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
5
5
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.4 Perinatal deaths
6
6
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.5 Neonatal deaths
7
7
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.6 Fetal deaths
8
8
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Respiratory distress syndrome
9
9
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Intraventricular haemorrhage.
10
10
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Mean birthweight (g)
11
11
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 Chorioamnionitis
12
12
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Endometritis.
13
13
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.30 Apgar < 7 at 5 minutes
14
14
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.25 Need for mechanical ventilation/CPAP
15
15
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.38 Proven infection while in the neonatal intensive care unit.
16
16
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.39 Necrotising enterocolitis.
1.1
1.1. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 1: Perinatal death
1.2
1.2. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 2: Neonatal death
1.3
1.3. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 3: Fetal death
1.4
1.4. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 4: Respiratory distress syndrome
1.5
1.5. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 5: Moderate/severe respiratory distress syndrome
1.6
1.6. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 6: Chronic lung disease
1.7
1.7. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 7: Intraventricular haemorrhage
1.8
1.8. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 8: Mean birthweight (g)
1.9
1.9. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 9: Maternal death
1.10
1.10. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 10: Chorioamnionitis
1.11
1.11. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 11: Endometritis
1.12
1.12. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 12: Death in childhood
1.13
1.13. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 13: Neurodevelopmental disability in childhood
1.14
1.14. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 14: Death into adulthood
1.15
1.15. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 15: Neurodevelopmental disability in adulthood
1.16
1.16. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 16: Fever in women after trial entry requiring the use of antibiotics
1.17
1.17. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 17: Intrapartum fever in woman requiring the use of antibiotics
1.18
1.18. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 18: Postnatal fever in woman
1.19
1.19. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 19: Admission into adult intensive care unit
1.20
1.20. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 20: Side effects of therapy in women
1.21
1.21. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 21: Glucose intolerance
1.22
1.22. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 22: Hypertension
1.23
1.23. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 23: Apgar < 7 at 5 minutes
1.24
1.24. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 24: Mean interval between trial entry and birth (days)
1.25
1.25. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 25: Mean length at birth (cm)
1.26
1.26. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 26: Mean head circumference at birth (cm)
1.27
1.27. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 27: Small‐for‐gestational age
1.28
1.28. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 28: Admission to neonatal intensive care unit
1.29
1.29. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 29: Need for mechanical ventilation/CPAP
1.30
1.30. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 30: Mean duration of mechanical ventilation/CPAP (days)
1.33
1.33. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 33: Air leak syndrome
1.34
1.34. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 34: Mean duration of oxygen supplementation (hours)
1.36
1.36. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 36: Surfactant use
1.37
1.37. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 37: Systemic infection in the first 48 hours of life
1.38
1.38. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 38: Proven infection while in the neonatal intensive care unit
1.39
1.39. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 39: Necrotising enterocolitis
1.40
1.40. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 40: Mean infant HPA axis function (cortisol)
1.41
1.41. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 41: Mean childhood weight (kg)
1.42
1.42. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 42: Mean childhood head circumference (cm)
1.43
1.43. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 43: Mean childhood height (cm)
1.44
1.44. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 44: Mean childhood systolic blood pressure (mmHg)
1.45
1.45. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 45: Cerebral palsy in childhood
1.46
1.46. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 46: Behavioural/learning difficulties in childhood
1.47
1.47. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 47: Mean adult weight (kg)
1.48
1.48. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 48: Mean adult head circumference (cm)
1.49
1.49. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 49: Mean adult height (cm)
1.50
1.50. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 50: Mean adult skinfold thickness (log values)
1.51
1.51. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 51: Abnormal lung function measured as forced vital capacity (adult)
1.52
1.52. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 52: Mean adult systolic blood pressure (mmHg)
1.53
1.53. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 53: Mean adult insulin (log values)
1.54
1.54. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 54: Mean adult glucose
1.55
1.55. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 55: Mean adult HPA axis function (mean log fasting cortisol)
1.56
1.56. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 56: Mean age at puberty (years)
1.57
1.57. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 57: Educational achievement by adulthood (university or polytechnic education)
1.58
1.58. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 58: Mean length of antenatal hospitalisation (days)
1.60
1.60. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 60: Mean length of postnatal hospitalisation (days)
1.61
1.61. Analysis
Comparison 1: Corticosteroids versus placebo or no treatment, Outcome 61: Mean length of neonatal hospitalisation (days)
2.1
2.1. Analysis
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1: Perinatal death ‐ single or multiple pregnancy
2.2
2.2. Analysis
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2: Neonatal death ‐ single or multiple pregnancy
2.3
2.3. Analysis
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3: Fetal death ‐ single or multiple pregnancy
2.4
2.4. Analysis
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4: Respiratory distress syndrome ‐ single or multiple pregnancy
2.5
2.5. Analysis
Comparison 2: Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5: Intraventricular haemorrhage ‐ single or multiple pregnancy
3.1
3.1. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 1: Perinatal death ‐ intact or ruptured membranes
3.2
3.2. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 2: Neonatal deaths ‐ intact or ruptured membranes
3.3
3.3. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 3: Fetal death ‐ intact or ruptured membranes
3.4
3.4. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 4: RDS ‐ intact or ruptured membranes
3.5
3.5. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 5: IVH ‐ intact or ruptured membranes
3.6
3.6. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 6: Birthweight ‐ intact or ruptured membranes
3.7
3.7. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 7: Chorioamnionitis ‐ intact or ruptured membranes
3.8
3.8. Analysis
Comparison 3: Corticosteroids versus placebo or no treatment ‐ intact membranes versus ruptured membranes at first dose, Outcome 8: Endometritis ‐ intact or ruptured membranes
4.1
4.1. Analysis
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1: Perinatal deaths ‐ hypertension syndrome vs other trials
4.2
4.2. Analysis
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2: Neonatal deaths ‐ hypertension syndrome vs other trials
4.3
4.3. Analysis
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3: Fetal deaths ‐ hypertension syndrome vs other trials
4.4
4.4. Analysis
Comparison 4: Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4: Respiratory distress syndrome ‐ hypertension syndrome vs other trials
5.1
5.1. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1: Perinatal death ‐ type of steroid
5.2
5.2. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2: Neonatal death ‐ type of steroid
5.3
5.3. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3: Fetal death ‐ type of steroid
5.4
5.4. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4: Respiratory distress syndrome ‐ type of steroid
5.5
5.5. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5: Moderate/severe respiratory distress syndrome ‐ type of steroid
5.6
5.6. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6: Chronic lung disease ‐ type of steroid
5.7
5.7. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7: IVH ‐ type of steroid
5.8
5.8. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8: Birthweight ‐ type of steroid
5.9
5.9. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9: Chorioamnionitis ‐ type of steroid
5.10
5.10. Analysis
Comparison 5: Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10: Endometritis ‐ type of steroid
6.1
6.1. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1: Perinatal death ‐ decade of trial
6.2
6.2. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2: Neonatal death ‐ decade of trial
6.3
6.3. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3: Fetal death ‐ decade of trial
6.4
6.4. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4: Respiratory distress syndrome ‐ decade of trial
6.5
6.5. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5: IVH ‐ decade of trial
6.6
6.6. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6: Birthweight ‐ decade of trial
6.7
6.7. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7: Chorioamnionitis ‐ decade of trial
6.8
6.8. Analysis
Comparison 6: Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8: Endometritis ‐ decade of trial
7.1
7.1. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1: Perinatal death ‐ protocol with weekly repeats
7.2
7.2. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2: Neonatal death ‐ protocol with weekly repeats
7.3
7.3. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3: Fetal death ‐ protocol with weekly repeats
7.4
7.4. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4: Respiratory distress syndrome ‐ protocol with weekly repeats
7.5
7.5. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5: Moderate/severe respiratory distress syndrome
7.6
7.6. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6: IVH ‐ protocol with weekly repeats
7.7
7.7. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7: Birthweight ‐ protocol with weekly repeats
7.8
7.8. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8: Chorioamnionitis ‐ protocol with weekly repeats
7.9
7.9. Analysis
Comparison 7: Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9: Endometritis ‐ protocol with weekly repeats
8.1
8.1. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1: Perinatal death ‐ gestational age at trial entry
8.2
8.2. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 2: Neonatal death ‐ gestational age at trial entry
8.3
8.3. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 3: Fetal death ‐ gestational age at trial entry
8.4
8.4. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 4: Respiratory distress syndrome ‐ gestational age at trial entry
8.5
8.5. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5: IVH ‐ gestational age at trial entry
8.6
8.6. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6: Birthweight ‐ gestational age at trial entry
8.7
8.7. Analysis
Comparison 8: Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7: Chorioamnionitis ‐ gestational age at trial entry
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    1. Garite TJ, Rumney PJ, Briggs GG. A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24-28 weeks gestation. Surgery, Gynecology and Obstetrics 1993;176:37. - PubMed
Gyamfi‐Bannerman 2016 {published data only}
    1. Battarbee Ashley N. 41: fetal metabolic biomarkers after late preterm betamethasone and their association with neonatal hypoglycemia. American Journal of Obstetrics and Gynecology 2020;222(1):S35-S36. [CENTRAL: CN-02074433] [EMBASE: 2004455290]
    1. Bicocca MJ, Chen H-Y, Blackwell S, Sibai B, Mfmu N. 457: does prepregnancy weight or maternal BMI at betamethasone administration impact late preterm respiratory morbidity? American Journal of Obstetrics and Gynecology 2019;220(1):S306-S307. [CENTRAL: CN-01758135] [EMBASE: 2001405365] - PubMed
    1. Carpenter J, Jablonski K, Koncinsky J, Varner M, Joss-Moore L. Antenatal steroids do not affect splicing or DNA methylation of the glucocorticoid receptor gene in cord blood T-cells. Reproductive Sciences (Thousand Oaks, Calif.) 2017;24(Suppl 1):258A. [CENTRAL: CN-01363475] [EMBASE: 615322896] - PMC - PubMed
    1. Doty MS, Chen H-Y, Chauhan SP, Sibai BM. 464: time interval from betamethasone to delivery among women at risk for late preterm delivery. American Journal of Obstetrics and Gynecology 2019;220(1):S310-1. [CENTRAL: CN-01710941] [EMBASE: 2001405276]
    1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. New England Journal of Medicine 2016;374(14):1311-20. - PMC - PubMed
Kari 1994 {published data only}
    1. Eronen M, Kari A, Pesonen E, Hallman M. The effect of antenatal dexamethasone administration on the fetal and neonatal ductus arteriosus: a randomised double-blind study. American Journal of Diseases of Children 1993;147:187-92. - PubMed
    1. Kari MA, Akino T, Hallman M. Prenatal dexamethasone (DEX) treatment before preterm delivery and rescue therapy of exogenous surfactant- surfactant components and surface activity in airway specimens (AS). In: Proceedings of the 14th European Congress of Perinatal Medicine; 1994 June 5-8; Helsinki, Finland. 1994:Abstract no: 486.
    1. Kari MA, Hallman M, Eronen M, Teramo K, Virtanen M, Koivisto M, et al. Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomised placebo-controlled multicenter study. Pediatrics 1994;93:730-6. - PubMed
    1. Salokorpi T, Sajaniemi N, Hallback H, Kari A, Rita H, Wendt L. Randomized study of the effect of antenatal dexamethasone on growth and development of premature children at the corrected age of 2 years. Acta Paediatrica 1997;86:294-8. - PubMed
Lewis 1996 {published data only}
    1. Lewis D, Brody K, Edwards M, Brouillette RM, Burlison S, London SN. Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics. Obstetrics & Gynecology 1996;88(5):801-5. - PubMed
Liggins 1972b {published and unpublished data}
    1. Dalziel SR, Fenwick S, Cundy T, Parag V, Beck TJ, Rodgers A, et al. Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial. Journal of Bone & Mineral Research 2006;21(8):1175-86. - PubMed
    1. Dalziel SR, Liang A, Parag V, Rodgers A, Harding JE. Blood pressure at 6 years of age after prenatal exposure to betamethasone: follow-up results of a randomized, controlled trial. Pediatrics 2004;114:e373-e377. - PubMed
    1. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial. BMJ 2005;331:665. - PMC - PubMed
    1. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Psychological functioning and health-related quality of life in adulthood after preterm birth. Developmental Medicine and Child Neurology 2007;49(8):597-602. - PubMed
    1. Dalziel SR, Parag V, Harding JE. Blood pressure at 6 years of age following exposure to antenatal betamethasone. In: 7th Annual Congress of the Perinatal Society of Australia and New Zealand; 2003 March 9-12; Tasmania, Australia. 2003:P13.
Lopez 1989 {published data only}
    1. Lopez AL, Rojas RL, Rodriguez MV, Sanchez AJ. Use of corticoids in preterm pregnancy with premature rupture of membranes [Uso de los corticoides en embarazo pretermino con ruptura prematura de membranas]. Revista Colombiana de Obstetricia y Ginecologia 1989;40:147-51.
Mansouri 2010 {published data only}
    1. IRCT138901193666N1. Effect of antenatal betamethasone on prevention of respiratory distress syndrome among neonates with gestational age of 35-36 weeks. www.irct.ir (Date first received: 17 May 2010).
    1. Mansouri M, Seyedolshohadaei F, Company F, Setare S, Mazhari S. Effect of antenatal betamethasone on prevention of respiratory distress syndrome among neonates with gestational age of 35-36 weeks. Journal of Gorgan University of Medical Sciences 2010;12(3):18-23.
Morales 1989 {published data only}
    1. Morales WJ, Angel JL, O'Brien WF, Knuppel RA. Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. Obstetrics & Gynecology 1989;73:721-6. - PubMed
Morrison 1978 {published data only}
    1. Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET. Effect of corticosteroids and fetomaternal disorders on the L:S ratio. Obstetrics & Gynecology 1980;56:583-90. - PubMed
    1. Morrison JC, Schneider JM, Whybrew WD, Bucovaz ET. Effect of corticosteroids and fetomaternal disorders on the L:S ratio. Surgery, Gynecology and Obstetrics 1981;153:464. - PubMed
    1. Morrison JC, Whybrew WD, Bucovaz ET, Scheiner JM. Injection of corticosteroids into mother to prevent neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1978;131:358-66. - PubMed
Nelson 1985 {published data only}
    1. Nelson LH, Meis PJ, Hatjis CG, Ernest JM, Dillard R, Schey HM. Premature rupture of membranes: a prospective randomized evaluation of steroids, latent phase and expectant management. Obstetrics & Gynecology 1985;66:55-8. - PubMed
Ontela 2018 {published data only}
    1. CTRI/2016/12/007570. Effct of antenatal corticosteroids on respiratory morbidity in late preterm newborns - a randomized controlled trial. http://www.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2016/12/007570 2016. [CENTRAL: CN-01807588]
    1. Dorairajan G, Ontela V, Vishnu B, Chinnakali P. Effect of antenatal steroids on respiratory morbidity of late preterm new-borns: a randomized controlled trial. https://epostersonline.com/rcog2018/node/58?view=true (accessed 4 September 2020). - PubMed
    1. Dorairajan G, Ontella V, Bhat V, Chinnakali P. Effect of antenatal dexamethasone on respiratory morbidity of late preterm newborns: a randomized controlled trial. BJOG: an international journal of obstetrics and gynaecology 2018;125(Suppl 1):67-8. [CENTRAL: CN-01571886] [EMBASE: 621569896]
    1. Ontela V, Dorairajan G, Bhat VB, Chinnakali P. Effect of antenatal steroids on respiratory morbidity of late preterm newborns: a randomized controlled trial. Journal of Tropical Pediatrics 2018;64(6):531-8. [CENTRAL: CN-01991657] [EMBASE: 626300500] [PMID: ] - PubMed
Porto 2011 {published data only}
    1. Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011;342:d1696. - PMC - PubMed
Qublan 2001 {published data only}
    1. Qublan H, Malkawi H, Hiasat M, Hindawi IM, Al-Taani MI, Abu-Khait SA, et al. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. Clinical & Experimental Obstetrics & Gynecology 2001;28(3):183-6. - PubMed
Schmidt 1984 {published data only}
    1. Schmidt PL, Sims ME, Strassner HT, Paul RH, Mueller E, McCart D. Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal infection. American Journal of Obstetrics and Gynecology 1984;148:178-86. - PubMed
Schutte 1980 {published data only}
    1. Dessens AB, Haas HS, Koppe JG. Twenty year follow up of antenatal corticosteroid treatment. Pediatrics 2000;105(6):1325. - PubMed
    1. Dessens AB, Smolders-de Haas H, Koppe JG. Twenty year follow up in antenatally corticosteroid-treated subjects. Prenatal and Neonatal Medicine 1998;3 Suppl 1:32.
    1. Schmand B, Neuvel J, Smolder-de Haas H, Hoeks J, Treffers PE, Koppe JG. Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. Pediatrics 1990;86:58-64. - PubMed
    1. Schutte MF, Koppe JG, Treffers PE, Breur W. The influence of 'treatment' in premature delivery on incidence of RDS. In: Proceedings of the 6th European Congress of Perinatal Medicine; 1978 Aug 29-Sept 1; Vienna, Austria. 1978:Abstract no: 80.
    1. Schutte MF, Treffers PE, Koppe JG, Breur W, Filedt Kok JC. The clinical use of corticosteroids for the acceleration of fetal lung maturity [Klinische toepassing van corticosteroiden ter bevordering van de foetale long-rijpheid]. Nederlands Tijdschrift voor Geneeskunde 1979;123(11):420-7. - PubMed
Shanks 2010 {published data only}
    1. Shanks A, Gross G, Shim T, Allsworth J, Moga C, Sadovsky Y, et al. Antenatal steroids for enhancement of fetal lung maturity after 34 weeks: lung maturity and antenatal steroids (LUMAS) study. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S58. - PMC - PubMed
    1. Shanks A, Gross G, Shim T, Allsworth J, Sadovsky Y, Bildirici I. Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles. American Journal of Obstetrics and Gynecology 2010;203(1):47.e1-47.e5. - PMC - PubMed
Silver 1996 {published data only}
    1. Silver RK, Vyskocil CR, Solomon SL, Farrell EE, MacGregor SN, Neerhof MG. Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered prior to 30 weeks of gestation. American Journal of Obstetrics and Gynecology 1995;172:254. - PubMed
    1. Silver RK, Vyskocil CR, Solomon SL, Ragin A, Neerhof MG, Farrell EE. Randomized trial of antenatal dexamethasone in surfactant-treated infants delivered prior to 30 weeks of gestation. Obstetrics & Gynecology 1996;87:683-91. - PubMed
Teramo 1980 {published data only}
    1. Teramo K, Hallman M, Raivio KO. Maternal glucocorticoid in unplanned premature labor. Pediatric Research 1980;14:326-9. - PubMed
WHO 2020 {published and unpublished data}
    1. ACTRN12617000476336. The WHO ACTION-I (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries to improve newborn outcomes. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12617000476336 (first received 2017) 2017. [CENTRAL: CN-01812305] - PMC - PubMed
    1. WHO ACTION Trials Collaborators. Antenatal dexamethasone for early preterm birth in low-resource countries. New England Journal of Medicine 2020;October 23:DOI: 10.1056/NEJMoa2022398. - PMC - PubMed
    1. WHO ACTION Trials Collaborators. The World Health Organization ACTION-I (Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries. Trials 2019;20(1):507. [CENTRAL: CN-02010986] [EMBASE: 628924308] [PMID: ] - PMC - PubMed

References to studies excluded from this review

Abuhamad 1999 {published data only}
    1. Abuhamad A, Green G, Heyl P, Veciana M. The combined use of corticosteroids and thyrotropin releasing hormone in pregnancies with preterm rupture of membranes: a randomised double blind controlled trial. American Journal of Obstetrics and Gynecology 1999;180(1 Pt 2):S96.
Althabe 2015 {published data only}
    1. Althabe F, Belizan JM, Mazzoni A, Berrueta M, Hemingway-Foday J, Koso-Thomas M, et al. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol. Reproductive Health 2012;9(1):22. - PMC - PubMed
    1. Althabe F, Belizan JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet 2015;385(9968):629-39. [PMID: ] - PMC - PubMed
    1. Goldenberg RL, Thorsten VR, Althabe F, Saleem S, Garces A, Carlo WA, et al. The global network antenatal corticosteroids trial: impact on stillbirth. Reproductive Health 2016;13(1):68. [CENTRAL: CN-01368862] [EMBASE: 610555843] [PMID: ] - PMC - PubMed
    1. NCT01084096. Trial of the use of antenatal corticosteroids in developing countries. https://clinicaltrials.gov/ct2/show/NCT01084096 (first received 2010).
Asnafei 2004 {published data only}
    1. Asnafei N, Pourreza R, Miri SM. Pregnancy outcome in premature delivery of between 34-37 weeks and the effects of corticosteroid on it. Journal of the Gorgan University of Medical Sciences 2004;6(2):57-60.
Butterfill 1979 {published data only}
    1. Butterfill AM, Harvey DR. Follow-up study of babies exposed to betamethasone before birth. Archives of Disease in Childhood 1979;54:725.
Dola 1997 {published data only}
    1. Dola C, Nageotte M, Rumney P, Towers C, Asrat T, Freeman R, et al. The effect of antenatal treatment with betamethasone and thyrotropin releasing hormone in patients with preterm premature rupture of membranes. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S49.
Dude 2016 {published data only}
    1. Dude C, Dude A, Gilner J, Swamy G, Grotegut C. Predicting preterm delivery: using the MFMU BEARS trial data to optimize corticosteroid use in women at risk for preterm delivery. Reproductive Sciences (Thousand Oaks, Calif.) 2016;23(Suppl 1):188A-9A. [CENTRAL: CN-02011932]
Egerman 1998 {published data only}
    1. Egerman RS, Mercer B, Doss JL, Sibai BM. A randomized controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S19. - PubMed
    1. Egerman RS, Mercer BM, Doss JL, Sibai BM. A randomized, controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1998;179(5):1120-3. - PubMed
    1. Egerman RS, Pierce WF 4th, Andersen RN, Umstot ES, Carr TL, Sibai BM. A comparison of the bioavailability of oral and intramuscular dexamethasone in women in late pregnancy. Obstetrics & Gynecology 1997;89(2):276-80. - PubMed
    1. Egerman RS, Walker RA, Doss JL, Mercer B, Sibai BM, Andersen RN. A comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S182. - PubMed
    1. Egerman RS, Walker RA, Mercer BM, Doss JL, Sibai BM, Andersen RA. Comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester. American Journal of Obstetrics and Gynecology 1998;179(5):1234-6. - PubMed
Garite 1981 {published data only}
    1. Garite TJ, Freeman RK, Linzey EM, Braly PS, Dorchester WL. Prospective randomized study of corticosteroids in the management of premature rupture of the membranes and the premature gestation. American Journal of Obstetrics and Gynecology 1981;141:508-15. - PubMed
Grgic 2003 {published data only}
    1. Grgic G, Fatusic Z, Bogdanovic G. Stimulation of fetal lung maturation with dexamethasone in unexpected premature labor. Medicinski Arhiv 2003;57(5-6):291-4. - PubMed
Halac 1990 {published data only}
    1. Halac E, Halac J, Begue EF, Casanas JM, Idiveri DR, Petit JF, et al. Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. Journal of Pediatrics 1990;117:132-8. - PubMed
Iams 1985 {published data only}
    1. Iams JD, Talbert ML, Barrows H, Sachs L. Management of preterm prematurely ruptured membranes: a prospective randomized comparison of observation vs use of steroids and timed delivery. American Journal of Obstetrics and Gynecology 1985;151:32-8. - PubMed
Khandelwal 2012 {published data only}
    1. Khandelwal M, Chang E, Hansen C, Hunter K, Milcarek B. Betamethasone dosing interval -12 or 24 hours apart? American Journal of Obstetrics and Gynecology 2012;206(Suppl 1):S10-S11. - PubMed
    1. Khandelwal M, Chang E, Hansen C, Hunter K, Milcarek B. Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial. American Journal of Obstetrics and Gynecology 2012;206(3):201.e1-11. - PubMed
Koivisto 2007 {published data only}
    1. Koivisto M, Peltoniemi OM, Saarela T, Tammela O, Jouppila P, Hallman M. Blood glucose level in preterm infants after antenatal exposure to glucocorticoid. Acta Paediatrica 2007;96(5):664-8. - PubMed
Kuhn 1982 {published data only}
    1. Kuhn RJP, Speirs AL, Pepperell RJ, Eggers TR, Doyle LW, Hutchinson A. Betamethasone, albuterol and threatened premature delivery. Obstetrics & Gynecology 1982;60:403-8. - PubMed
Kurtzman 2008 {published data only}
    1. Kurtzman J, Garite T, Clark R, Maurel K, The OCRN. Impact of a 'rescue course' of antenatal corticosteroids (ACS): a multi-center randomized placebo controlled trial. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S2. - PubMed
Liu 2006 {published data only}
    1. Liu J, Wang Q, Zhao JH, Chen YH, Qin GL. The combined antenatal corticosteroids and vitamin K therapy for preventing periventricular-intraventricular hemorrhage in premature newborns less than 35 weeks gestation. Journal of Tropical Pediatrics 2006;52(5):355-9. - PubMed
Magee 1997 {published data only}
    1. Magee LA, Dawes GS, Moulden M, Redman CW. A randomised controlled comparison of betamethasone with dexamethasone: effects on the antenatal fetal heart rate. British Journal of Obstetrics and Gynaecology 1997;104(11):1233-8. - PubMed
Maksic 2008 {published data only}
    1. Maksic H, Hadzagic-Catibusic F, Heljic S, Dizdarevic J. The effects of antenatal corticosteroid treatment on IVH-PVH of premature infants. Bosnian Journal of Basic Medical Sciences 2008;8(1):58-62. - PMC - PubMed
McEvoy 2010 {published data only}
    1. McEvoy C, Schilling D, Clay N, Spitale P, Durand M. Neurodevelopmental outcome and growth in infants randomized to a single rescue course of antenatal steroids. In: Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; 2011 April 30-May 3; Denver, Colorado, USA. 2011:3829.270.
    1. McEvoy C, Schilling D, Peters D, Tillotson C, Spitale P, Wallen L, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. American Journal of Obstetrics and Gynecology 2010;202(6):544.e1-9. - PMC - PubMed
    1. McEvoy C, Schilling D, Segel S, Spitale P, Wallen L, Bowling S, et al. Improved respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized trial. American Journal of Obstetrics and Gynecology 2008;199(6 Suppl 1):S228. - PMC - PubMed
    1. McEvoy C, Schilling D, Spitale P, Gravett M, Durand M. Pulmonary function and respiratory outcomes at 12-24 months in preterm infants randomized to a single rescue course of antenatal steroids. In: Pediatric Academic Societies' 2010 Annual Meeting; 2010 May 1-4; Vancouver, Canada. 2010.
    1. McEvoy C, Schilling D, Spitale P, Wallen L, Segel S, Bowling S, et al. Improved respiratory compliance after a single rescue course of antenatal steroids: a randomized controlled trial. In: Pediatric Academic Societies Annual Meeting; 2007 May 5-8; Toronto, Canada. 2007.
Minoui 1998 {published data only}
    1. Minoui S, Ville Y, Senat M, Multon O, Fernandez H, Frydman R. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomized study. British Journal of Obstetrics and Gynaecology 1998;105:749-55. - PubMed
    1. Minoui S, Ville Y, Senat MV, Multon O, Fernandez H, Frydman R. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labor a randomized study. Prenatal and Neonatal Medicine 1996;1 Suppl 1:156. - PubMed
Morales 1986 {published data only}
    1. Morales WJ, Diebel D, Lazar AJ, Zadrozny D. The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with premature rupture of membranes. American Journal of Obstetrics and Gynecology 1986;154:591-5. - PubMed
Mulder 1997 {published data only}
    1. Mulder EJ, Derks JB, Visser GH. Antenatal corticosteroid therapy and fetal behaviour: a randomised evaluation of betamethasone and dexamethasone. British Journal of Obstetrics and Gynaecology 1997;104(11):1239-47. - PubMed
NCT02351310 2015 {published data only}
    1. NCT02351310. Effectiveness of ACS in extreme preemies [Effects of antenatal corticosteroids in patients with early (22 - 23w6d) threatened preterm birth]. Https://clinicaltrials.gov/show/NCT02351310 (first received 2015 Jan 27). [CENTRAL: CN-01551840]
NCT04494529 2020 {published data only}
    1. NCT04494529. Single Dose Antenatal Corticosteroids (SNACS) for women at risk of preterm birth [Single Dose Antenatal Corticosteroids (SNACS) pilot randomized control trial for women at risk of preterm birth]. https://clinicaltrials.gov/show/NCT04494529 (first received 2020 Jul 31). [CENTRAL: CN-02145746]
Papageorgiou 1979 {published data only}
    1. Papageorgiou AN, Desgranges MF, Masson M, Colle E, Shatz R, Gelfand MM. The antenatal use of betamethasone in the prevention of respiratory distress syndrome: a controlled blind study. Pediatrics 1979;63:73-9. - PubMed
Romejko‐Wolniewicz 2013 {published data only}
    1. Romejko-Wolniewicz E, Oleszczuk L, Zareba-Szczudlik J, Czajkowski K. Dosage regimen of antenatal steroids prior to preterm delivery and effects on maternal and neonatal outcomes. Journal of Maternal-Fetal and Neonatal Medicine 2013;26(3):237-41. - PubMed
Rotmensch 1999 {published data only}
    1. Rotmensch S, Liberati M, Vishne T, Celentano C, Ben-Rafael Z, Bellati U. The effects of betamethasone versus dexamethasone on computer-analysed fetal heart rate characteristics: a prospective randomized trial. American Journal of Obstetrics and Gynecology 1998;178(1 Pt 2):S185.
    1. Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U. The effect of betamethasone and dexamethasone on the fetal heart rate patterns and biophysical activities. A prospective randomized trial. Acta Obstetricia et Gynecologica Scandinavica 1999;78(6):493-500. - PubMed
Simpson 1985 {published data only}
    1. Simpson G, Harbert G. Use of beta-methasone in management of preterm gestation with premature rupture of membranes. Obstetrics & Gynecology 1985;66:168-75. - PubMed
Whitt 1976 {published data only}
    1. Whitt GG, Buster JE, Killam AP, Scragg WH. A comparison of two glucocorticoid regimens for acceleration of fetal lung maturation in premature labor. American Journal of Obstetrics and Gynecology 1976;124:479-82. - PubMed

References to studies awaiting assessment

Cararach 1991 {published data only}
    1. Botet F, Cararach V, Sentis J. Premature rupture of membranes in early pregnancy. Neonatal prognosis. Journal of Perinatal Medicine 1994;22:45-52. - PubMed
    1. Cararach V, Botet F, Sentis J, Carmona F. A multicenter, prospective randomized study in premature rupture of membranes (PROM). Maternal and perinatal complications. International Journal of Gynecology and Obstetrics 1991;36 Suppl:267.
    1. Cararach V, Sentis J, Botet F, De Los Rios L. A multicenter, prospective randomized study in premature rupture of membranes (PROM). Respiratory and infectious complications in the newborn. In: Proceedings of the 12th European Congress of Perinatal Medicine; 1990; Lyon, France. 1990:216.
Carlan 1991 {published data only}
    1. Carlan SJ, Parsons M, O'Brien WF, Krammer J. Pharmacologic pulmonary maturation in preterm premature rupture of membranes. American Journal of Obstetrics and Gynecology 1991;164:371.
Delibas 2017 {published data only}
    1. Delibas IB, Ingec M, Yapca OE. Does antenatal betamethasone have negative effects on fetal activities and hemodynamics in cases of preeclampsia without severe features? A prospective, placebo-controlled, randomized study. Journal of Maternal-fetal & Neonatal Medicine 2016 Nov;30(22):2671-8. [CENTRAL: CN-01602216] [PMID: ] - PubMed
Doran 1980 {published data only}
    1. Doran TA, Swyer P, MacMurray B, Mahon W, Enhorning G, Bernstein A, et al. Results of a double blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome. American Journal of Obstetrics and Gynecology 1980;136:313-20. - PubMed
Goodner 1979 {published data only}
    1. Goodner DM. Antenatal steroids in the treatment of respiratory distress syndrome. In: 9th World Congress of Gynecology and Obstetrics; 1979 October 26-31; Tokyo, Japan. 1979:362.
Khazardoust 2012 {published data only}
    1. Hantoushzadeh S, Javadian P, Salmanian B, Ghazanfari T, Kermani A, Abbasalizadeh F, et al. Betamethasone effects on the endocervical inflammatory cytokines in preterm labor: a randomized clinical trial. International Immunopharmacology 2011;11(8):1116-9. - PubMed
    1. Khazardoust S, Javadian P, Salmanian B, Zandevakil F, Abbasalizadeh F, Alimohamadi S, et al. A clinical randomized trial on endocervical inflammatory cytokines and Betamethasone in prime-gravid pregnant women at risk of preterm labor. Iranian Journal of Immunology 2012;9(3):199-207. - PubMed
Mirzamoradi 2019 {published data only}
    1. IRCT20120918010876N3. Assessment of efficacy of antenatal betamethasone on neonatal respiratory outcome of late preterm delivery (34-37 weeks) [Assessment of efficacy of antenatal betamethasone on neonatal respiratory outcome of late preterm delivery (34-37 weeks) in singleton pregnancies]. http://www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20120918010876N3 2017. [CENTRAL: CN-01898197]
    1. Mirzamoradi M, Hasani NF, Jamali R, Heidar Z, Bakhtiyari M. Evaluation of the effect of antenatal betamethasone on neonatal respiratory morbidities in late preterm deliveries (34-37 weeks). Journal of Maternal-fetal & Neonatal Medicine 2019;33(15):2533-40. [CENTRAL: CN-01787845] [EMBASE: 625854285] [PMID: ] - PubMed
Parsons 1988 {published data only}
    1. Parsons MT, Sobel D, Cummiskey K, Constantine L, Roitman J. Steroid, antibiotic and tocolytic vs no steroid, antibiotic and tocolytic management in patients with preterm PROM at 25-32 weeks. In: Proceedings of the 8th Annual Meeting of the Society of Perinatal Obstetricians; 1988 Feb 3-6; Las Vegas, Nevada. 1988:44.
    1. Sobel D, Parsons M, Roitman J, McAlpine L, Cumminsky K. Antenatal antibiotics in PROM prevents congenital bacterial infection. Pediatric Research 1988;23:476A.
Taeusch 1979 {published data only}
    1. Taeusch HW Jr, Frigoletto F, Kitzmiller J, Avery ME, Hehre A, Fromm B, et al. Risk of respiratory distress syndrome after prenatal dexamethasone treatment. Pediatrics 1979;63:64-72. - PubMed

References to ongoing studies

ACTRN12617001494325 2017 {published data only}
    1. ACTRN12617001494325. The WHO ACTION-II (Antenatal CorticosTeroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial of antenatal corticosteroids for women at risk of imminent birth in the late preterm period in hospitals in low-resource countries to improve newborn outcomes. http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12617001494325 2017. [CENTRAL: CN-01884536] - PMC - PubMed
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