Meta-Analysis

. 2017 Mar 21;3(3):CD004454.

doi: 10.1002/14651858.CD004454.pub3.

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

Devender Roberts¹, Julie Brown², Nancy Medley³, Stuart R Dalziel^{2

4}

Affiliations

¹ Obstetrics Directorate, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, Merseyside, UK, L8 7SS.
² Liggins Institute, The University of Auckland, Park Rd, Grafton, Auckland, New Zealand, 1142.
³ Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, The University of Liverpool, First Floor, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, UK, L8 7SS.
⁴ Children's Emergency Department, Starship Children's Health, Auckland, New Zealand.

PMID: 28321847
PMCID: PMC6464568
DOI: 10.1002/14651858.CD004454.pub3

Meta-Analysis

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

Devender Roberts et al. Cochrane Database Syst Rev. 2017.

. 2017 Mar 21;3(3):CD004454.

doi: 10.1002/14651858.CD004454.pub3.

Authors

Devender Roberts¹, Julie Brown², Nancy Medley³, Stuart R Dalziel^{2

4}

Affiliations

¹ Obstetrics Directorate, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, Merseyside, UK, L8 7SS.
² Liggins Institute, The University of Auckland, Park Rd, Grafton, Auckland, New Zealand, 1142.
³ Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, The University of Liverpool, First Floor, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, UK, L8 7SS.
⁴ Children's Emergency Department, Starship Children's Health, Auckland, New Zealand.

PMID: 28321847
PMCID: PMC6464568
DOI: 10.1002/14651858.CD004454.pub3

Update in

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.
McGoldrick E, Stewart F, Parker R, Dalziel SR. McGoldrick E, et al. Cochrane Database Syst Rev. 2020 Dec 25;12(12):CD004454. doi: 10.1002/14651858.CD004454.pub4. Cochrane Database Syst Rev. 2020. PMID: 33368142 Free PMC article.

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. While researching the effects of the steroid dexamethasone on premature parturition in fetal sheep in 1969, Liggins found that there was some inflation of the lungs of lambs born at gestations at which the lungs would be expected to be airless. Liggins and Howie published the first randomised controlled trial in humans in 1972 and many others followed.

Objectives: To assess the effects of administering a course of corticosteroids to the mother prior to anticipated preterm birth on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.

Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (17 February 2016) and reference lists of retrieved studies.

Selection criteria: We considered all randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following spontaneous labour), regardless of other co-morbidity, for inclusion in this review. Most women in this review received a single course of steroids; however, nine of the included trials allowed for women to have weekly repeats.

Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.

Main results: This update includes 30 studies (7774 women and 8158 infants). Most studies are of low or unclear risk for most bias domains. An assessment of high risk usually meant a trial had potential for performance bias due to lack of blinding. Two trials had low risks of bias for all risk of bias domains.Treatment with antenatal corticosteroids (compared with placebo or no treatment) is associated with a reduction in the most serious adverse outcomes related to prematurity, including: perinatal death (average risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.89; participants = 6729; studies = 15; Tau² = 0.05, I² = 34%; moderate-quality); neonatal death (RR 0.69, 95% CI 0.59 to 0.81; participants = 7188; studies = 22), RDS (average RR 0.66, 95% CI 0.56 to 0.77; participants = 7764; studies = 28; Tau² = 0.06, I² = 48%; moderate-quality); moderate/severe RDS (average RR 0.59, 95% CI 0.38 to 0.91; participants = 1686; studies = 6; Tau² = 0.14, I² = 52%); intraventricular haemorrhage (IVH) (average RR 0.55, 95% CI 0.40 to 0.76; participants = 6093; studies = 16; Tau² = 0.10, I² = 33%; moderate-quality), necrotising enterocolitis (RR 0.50, 95% CI 0.32 to 0.78; participants = 4702; studies = 10); need for mechanical ventilation (RR 0.68, 95% CI 0.56 to 0.84; participants = 1368; studies = 9); and systemic infections in the first 48 hours of life (RR 0.60, 95% CI 0.41 to 0.88; participants = 1753; studies = 8).There was no obvious benefit for: chronic lung disease (average RR 0.86, 95% CI 0.42 to 1.79; participants = 818; studies = 6; Tau² = 0.38 I² = 65%); mean birthweight (g) (MD -18.47, 95% CI -40.83 to 3.90; participants = 6182; studies = 16; moderate-quality); death in childhood (RR 0.68, 95% CI 0.36 to 1.27; participants = 1010; studies = 4); neurodevelopment delay in childhood (RR 0.64, 95% CI 0.14 to 2.98; participants = 82; studies = 1); or death into adulthood (RR 1.00, 95% CI 0.56 to 1.81; participants = 988; studies = 1).Treatment with antenatal corticosteroids does not increase the risk of chorioamnionitis (RR 0.83, 95% CI 0.66 to 1.06; participants = 5546; studies = 15; moderate-quality evidence) or endometritis (RR 1.20, 95% CI 0.87 to 1.63; participants = 4030; studies = 10; Tau² = 0.11, I² = 28%; moderate-quality). No increased risk in maternal death was observed. However, the data on maternal death is based on data from a single trial with two deaths; four other trials reporting maternal death had zero events (participants = 3392; studies = 5; moderate-quality).There is no definitive evidence to suggest that antenatal corticosteroids work differently in any pre-specified subgroups (singleton versus multiple pregnancy; membrane status; presence of hypertension) or for different study protocols (type of corticosteroid; single course or weekly repeats).GRADE outcomes were downgraded to moderate-quality. Downgrading decisions (for perinatal death, RDS, IVH, and mean birthweight) were due to limitations in study design or concerns regarding precision (chorioamnionitis, endometritis). Maternal death was downgraded for imprecision due to few events.

Authors' conclusions: Evidence from this update supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids could be considered routine for preterm delivery. It is important to note that most of the evidence comes from high income countries and hospital settings; therefore, the results may not be applicable to low-resource settings with high rates of infections.There is little need for further trials of a single course of antenatal corticosteroids versus placebo in singleton pregnancies in higher income countries and hospital settings. However, data are sparse in lower income settings. There are also few data regarding risks and benefits of antenatal corticosteroids in multiple pregnancies and other high-risk obstetric groups. Further information is also required concerning the optimal dose-to-delivery interval, and the optimal corticosteroid to use.We encourage authors of previous studies to provide further information, which may answer any remaining questions about the use of antenatal corticosteroids in such pregnancies without the need for further randomised controlled trials. Individual patient data meta-analysis from published trials is likely to answer some of the evidence gaps. Follow-up studies into childhood and adulthood, particularly in the late preterm gestation and repeat courses groups, are needed. We have not examined the possible harmful effects of antenatal corticosteroids in low-resource settings in this review. It would be particularly relevant to explore this finding in adequately powered prospective trials.

PubMed Disclaimer

Conflict of interest statement

Devender Roberts: none known.

Julie Brown: none known.

Nancy Medley: Nancy Medley's work was financially supported by the a grant to University of Liverpool from the Harris‐Wellbeing Preterm Birth Centre.

Stuart R Dalziel: none known.

Figures

**Figure 1**
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

**Figure 2**
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

**Figure 3**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 Chorioamnionitis

**Figure 4**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.4 Perinatal deaths

**Figure 5**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.5 Neonatal deaths

**Figure 6**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.6 Fetal deaths

**Figure 7**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.7 Respiratory distress syndrome

**Figure 8**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.10 Intraventricular haemorrhage

**Figure 9**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.11 Mean birthweight (g)

**Figure 10**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.25 Need for mechanical ventilation/CPAP

**Figure 11**
Funnel plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.30 Apgar < 7 at 5 minutes

**Analysis 1.1**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 1 Maternal death.

**Analysis 1.2**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 2 Chorioamnionitis.

**Analysis 1.3**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 3 Endometritis.

**Analysis 1.4**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 4 Perinatal deaths.

**Analysis 1.5**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 5 Neonatal deaths.

**Analysis 1.6**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 6 Fetal deaths.

**Analysis 1.7**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 7 Respiratory distress syndrome.

**Analysis 1.8**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 8 Moderate/severe respiratory distress syndrome.

**Analysis 1.9**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 9 Chronic lung disease.

**Analysis 1.10**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 10 Intraventricular haemorrhage.

**Analysis 1.11**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 11 Mean birthweight (g).

**Analysis 1.12**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 12 Death in childhood.

**Analysis 1.13**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 13 Neurodevelopmental delay in childhood.

**Analysis 1.14**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 14 Death into adulthood.

**Analysis 1.15**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 15 Fever in women after trial entry requiring the use of antibiotics.

**Analysis 1.16**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 16 Intrapartum fever in woman requiring the use of antibiotics.

**Analysis 1.17**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 17 Side effects of therapy in women.

**Analysis 1.18**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 18 Admission into adult intensive care unit.

**Analysis 1.19**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 19 Hypertension.

**Analysis 1.20**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 20 Postnatal fever in woman.

**Analysis 1.21**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 21 Glucose intolerance.

**Analysis 1.22**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 22 Necrotising enterocolitis.

**Analysis 1.23**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 23 Systemic infection in the first 48 hours of life.

**Analysis 1.24**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 24 Proven infection while in the neonatal intensive care unit.

**Analysis 1.25**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 25 Need for mechanical ventilation/CPAP.

**Analysis 1.26**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 26 Mean duration of mechanical ventilation/CPAP (days).

**Analysis 1.27**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 27 Mean duration of oxygen supplementation (days).

**Analysis 1.28**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 28 Surfactant use.

**Analysis 1.29**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 29 Air leak syndrome.

**Analysis 1.30**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 30 Apgar < 7 at 5 minutes.

**Analysis 1.31**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 31 Mean interval between trial entry and birth (days).

**Analysis 1.32**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 32 Small‐for‐gestational age.

**Analysis 1.33**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 33 Mean infant HPA axis function (cortisol).

**Analysis 1.34**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 34 Admission to neonatal intensive care unit.

**Analysis 1.35**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 35 Developmental delay in childhood.

**Analysis 1.36**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 36 Cerebral palsy in childhood.

**Analysis 1.37**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 37 Mean childhood weight (kg).

**Analysis 1.38**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 38 Mean childhood height (cm).

**Analysis 1.39**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 39 Mean childhood head circumference (cm).

**Analysis 1.40**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 40 Mean childhood VC (% predicted).

**Analysis 1.41**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 41 Mean childhood FEV1 (% predicted).

**Analysis 1.42**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 42 Mean childhood FEV1/VC.

**Analysis 1.43**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 43 Mean childhood systolic blood pressure (mmHg).

**Analysis 1.44**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 44 Visual impairment in childhood.

**Analysis 1.45**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 45 Hearing impairment in childhood.

**Analysis 1.46**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 46 Intellectual impairment in childhood.

**Analysis 1.47**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 47 Behavioural/learning difficulties in childhood.

**Analysis 1.48**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 48 Mean adult insulin (log values).

**Analysis 1.49**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 49 Mean adult glucose (mmol/L).

**Analysis 1.50**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 50 Mean adult weight (kg).

**Analysis 1.51**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 51 Mean adult height (cm).

**Analysis 1.52**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 52 Mean adult head circumference (cm).

**Analysis 1.53**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 53 Mean adult skinfold thickness (log values).

**Analysis 1.54**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 54 Mean adult systolic blood pressure (mmHg).

**Analysis 1.55**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 55 Mean adult HPA axis function (mean log fasting cortisol).

**Analysis 1.56**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 56 Mean cholesterol in adulthood (mmol/L).

**Analysis 1.57**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 57 Mean age at puberty (years).

**Analysis 1.58**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 58 Educational achievement by adulthood (university or polytechnic education).

**Analysis 1.59**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 59 Visual impairment in adulthood.

**Analysis 1.60**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 60 Hearing impairment in adulthood.

**Analysis 1.61**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 61 Intellectual impairment in adulthood.

**Analysis 1.62**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 62 Mean adult FVC (% predicted).

**Analysis 1.63**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 63 Mean adult FEV1 (% predicted).

**Analysis 1.64**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 64 Mean adult FEV1/FVC.

**Analysis 1.65**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 65 Mean adult PEF.

**Analysis 1.66**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 66 Mean adult F50.

**Analysis 1.67**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 67 Mean adult F25.

**Analysis 1.68**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 68 Mean adult FEF 25%‐75%.

**Analysis 1.69**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 69 FEV1/FVC < 70%.

**Analysis 1.70**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 70 Asthma diagnosed by Doctor in lifetime.

**Analysis 1.71**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 71 Wheezing in last 12 months.

**Analysis 1.72**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 72 Current Asthma.

**Analysis 1.73**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 73 Further respiratory diagnosis (includes pneumonia, upper airway conditions and bronchitis).

**Analysis 1.74**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 74 Spontaneous pneumothorax.

**Analysis 1.75**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 75 Shortness of breath at anytime in the last 12 months.

**Analysis 1.76**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 76 Mean adult lumbar spine aBMD (g/cm2) areal bone mineral density.

**Analysis 1.77**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 77 Mean adult lumbar spine vBMD (g/cm3) volumetric bone mineral density.

**Analysis 1.78**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 78 Mean adult total body BMC (grams) bone mineral content.

**Analysis 1.79**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 79 Mean adult total body aBMD (g/cm3) areal bone mineral density.

**Analysis 1.80**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 80 Mean adult femoral neck aBMD (g/cm2) areal bone mineral density.

**Analysis 1.81**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 81 Mean adult femoral trochanter aBMD (g/cm2) areal bone mineral density.

**Analysis 1.82**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 82 Mean adult femoral shaft aBMD (g/cm2) areal bone mineral density.

**Analysis 1.83**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 83 Mean total proximal femur aBMD (g/cm2) areal bone mineral density.

**Analysis 1.84**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 84 Mean length of antenatal hospitalisation (days).

**Analysis 1.85**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 85 Mean length of postnatal hospitalisation (days).

**Analysis 1.86**
Comparison 1 Corticosteroids versus placebo or no treatment, Outcome 86 Mean length of neonatal hospitalisation (days).

**Analysis 2.1**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 1 Chorioamnionitis ‐ single or multiple pregnancy.

**Analysis 2.2**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 2 Perinatal death ‐ single or multiple pregnancy.

**Analysis 2.3**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 3 Neonatal death ‐ single or multiple pregnancy.

**Analysis 2.4**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 4 Fetal death ‐ single or multiple pregnancy.

**Analysis 2.5**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 5 Respiratory distress syndrome ‐ single or multiple pregnancy.

**Analysis 2.6**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 6 IVH ‐ single or multiple pregnancy.

**Analysis 2.7**
Comparison 2 Corticosteroids versus placebo or no treatment ‐ single or multiple pregnancy, Outcome 7 Birthweight ‐ single or multiple pregnancy.

**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.

**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.

**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.

**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.

**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.

**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.

**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.

**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.

**Analysis 4.1**
Comparison 4 Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 1 RDS.

**Analysis 4.2**
Comparison 4 Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 2 Perinatal deaths.

**Analysis 4.3**
Comparison 4 Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 3 Fetal deaths.

**Analysis 4.4**
Comparison 4 Corticosteroids versus placebo or no treatment ‐ hypertension syndrome versus all other trials, Outcome 4 Neonatal deaths.

**Analysis 5.1**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 1 Chorioamnionitis ‐ type of steroid.

**Analysis 5.2**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 2 Endometritis ‐ type of steroid.

**Analysis 5.3**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 3 Perinatal death ‐ type of steroid.

**Analysis 5.4**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 4 Neonatal deaths by steroid type.

**Analysis 5.5**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 5 Fetal death ‐ type of steroid.

**Analysis 5.6**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 6 Respiratory distress syndrome ‐ type of steroid.

**Analysis 5.7**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 7 IVH ‐ type of steroid.

**Analysis 5.8**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 8 Birthweight ‐ type of steroid.

**Analysis 5.9**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 9 Moderate/severe respiratory distress syndrome ‐ type of steroid.

**Analysis 5.10**
Comparison 5 Corticosteroids versus placebo or no treatment ‐ type of steroid, Outcome 10 Chronic lung disease ‐ type of steroid.

**Analysis 6.1**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 1 Chorioamnionitis ‐ decade of trial.

**Analysis 6.2**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 2 Endometritis ‐ decade of trial.

**Analysis 6.3**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 3 Perinatal deaths ‐ decade of trial.

**Analysis 6.4**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 4 Neonatal deaths decade of trial.

**Analysis 6.5**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 5 Fetal death ‐ decade of trial.

**Analysis 6.6**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 6 RDS ‐ decade of trial.

**Analysis 6.7**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 7 IVH ‐ decade of trial.

**Analysis 6.8**
Comparison 6 Corticosteroids versus placebo or no treatment ‐ decade of trial, Outcome 8 Birthweight ‐ decade of trial.

**Analysis 7.1**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 1 Chorioamnionitis ‐ Protocol with weekly repeats.

**Analysis 7.2**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 2 Endometritis ‐ protocol with weekly repeats.

**Analysis 7.3**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 3 Perinatal death ‐ protocol with weekly repeats.

**Analysis 7.4**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 4 Neonatal death ‐ protocol with weekly repeats.

**Analysis 7.5**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 5 Fetal death ‐ protocol with weekly repeats.

**Analysis 7.6**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 6 RDS ‐ protocol with weekly repeats.

**Analysis 7.7**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 7 IVH‐ protocol with weekly repeats.

**Analysis 7.8**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 8 Birthweight ‐ protocol with weekly repeats.

**Analysis 7.9**
Comparison 7 Corticosteroids versus placebo or no treatment ‐ weekly repeats, Outcome 9 Moderate/severe respiratory distress syndrome.

**Analysis 8.1**
Comparison 8 Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 1 Chorioamnionitis ‐ gestational age at trial entry.

**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.

**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.

**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.

**Analysis 8.5**
Comparison 8 Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 5 RDS‐ gestational age at trial entry.

**Analysis 8.6**
Comparison 8 Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 6 IVH ‐ gestational age at trial entry.

**Analysis 8.7**
Comparison 8 Corticosteroids versus placebo or no treatment ‐ gestational age at trial entry, Outcome 7 Birthweight ‐ gestational age at trial entry.

See this image and copyright information in PMC

Update of

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.
Roberts D, Dalziel S. Roberts D, et al. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004454. doi: 10.1002/14651858.CD004454.pub2. Cochrane Database Syst Rev. 2006. Update in: Cochrane Database Syst Rev. 2017 Mar 21;3:CD004454. doi: 10.1002/14651858.CD004454.pub3. PMID: 16856047 Updated.

Comment in

Corticosteroids for preterm deliveries: missing evidence.
Opiyo N, Stones W. Opiyo N, et al. Cochrane Database Syst Rev. 2017 May 3;5(5):ED000121. doi: 10.1002/14651858.ED000121. Cochrane Database Syst Rev. 2017. PMID: 28497861 Free PMC article. No abstract available.
The profile of a life-saving researcher.
Knightly R. Knightly R. Educ Prim Care. 2018 Mar;29(2):113-114. doi: 10.1080/14739879.2018.1437570. Epub 2018 Feb 15. Educ Prim Care. 2018. PMID: 29447583

References

References to studies included in this review

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1. Attawattanakul N, Tansupswatdikul P. Effects of antenatal dexamethasone on respiratory distress in late preterm infant: a randomized controlled trial. Thai Journal of Obstetrics and Gynaecology 2015;23:25‐33.
1. Balci O, Ozdemir S, Mahmoud AS, Acar A, Colakoglu MC. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecologic and Obstetric Investigation 2010;70(2):95‐9. - PubMed
1. Block MF, Kling OR, Crosby WM. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstetrics & Gynecology 1977;50:186‐90. - PubMed
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
2. 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.
3. Cararach V, Sentis J, Botet F, Rios L. A multicenter, prospective randomized study in premature rupture of membranes (PROM). Respiratory and infectious complications in the newborn. Proceedings of the 12th European Congress of Perinatal Medicine; 1990; Lyon, France. 1990:216.

References to studies excluded from this review

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.
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
2. Althabe F, Belizan JM, McClure EM, Hemingway‐Foday J, Berrueta M, Mazzoni A, et al. A population‐based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low‐income and middle‐income countries: the ACT cluster‐randomised trial. Lancet 2014;385(9968):629‐639. [PUBMED: 25458726] - PMC - PubMed
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.
1. Butterfill AM, Harvey DR. Follow‐up study of babies exposed to betamethasone before birth. Archives of Disease in Childhood 1979;54:725. - PubMed
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.

Additional references

1. Althabe F, Belizan J, McClure E, Hemingway‐Foday J, Berrueta M, Mazzoni A, et al. A population‐based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low‐income and middle‐income countries: the ACT cluster‐ randomised trial. The Lancet 2014;385(9968):629‐39. [DOI: 10.1016/S0140-6736(14)61651-2] - DOI - PMC - PubMed
1. Amiya RM, Mlunde LB, Ota E, Swa T, Oladapo O, Mori R. Antenatal corticosteroids for reducing adverse maternal and child outcomes in special populations of women at risk of imminent preterm birth: a systematic review and meta‐analysis. PLoS One 2016;11(2):e0147604. [DOI: 10.1371/journal.pone.0147604] - DOI - PMC - PubMed
1. Antenatal Corticosteroids Clinical Practice Guidelines Panel. Antenatal corticosteroids given to women prior to birth to improve fetal, infant, child and adult health: Clinical Practice Guidelines. Liggins Institute, The University of Auckland, Auckland, New Zealand2015.
1. Azad K, Costello A. Extreme caution is needed before scale‐up of antenatal corticosteroids to reduce preterm deaths in low‐income settings. Lancet 2014;2:e191‐e192. [DOI: 10.1016/S2214-109X(14)70020-8] - DOI - PubMed
1. Barker DJP. Mothers, Babies and Health in Later Life. 2nd Edition. London: Churchill Livingstone, 1998.

References to other published versions of this review

1. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD000065.pub2] - DOI - PMC - PubMed
1. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD004454.pub2] - DOI - PubMed

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

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