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. 2021 Dec 22;12(12):CD006614.
doi: 10.1002/14651858.CD006614.pub4.

Antenatal corticosteroids prior to planned caesarean at term for improving neonatal outcomes

Alexandros Sotiriadis  1 , Emma McGoldrick  2 , George Makrydimas  3 , Stefania Papatheodorou  4 , John Pa Ioannidis  5 , Fiona Stewart  6   7 , Roses Parker  8
Affiliations

Antenatal corticosteroids prior to planned caesarean at term for improving neonatal outcomes

Alexandros Sotiriadis et al. Cochrane Database Syst Rev. .

Abstract

Background: Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. It is unclear whether administration at term gestations, prior to caesarean section, improves the respiratory outcomes for these babies without causing any unnecessary morbidity to the mother or the infant.

Objectives: The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual care (which could be placebo or no treatment), on fetal, neonatal and maternal morbidity. We also assessed the impact of the treatment on the child in later life.

Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (20 January 2021) and reference lists of retrieved studies.

Selection criteria: We included randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation). Quasi-randomised and cluster-randomised controlled trials were also eligible for inclusion.

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. Our primary outcomes were respiratory distress syndrome (RDS), transient tachypnoea of the neonate (TTN), admission to neonatal special care for respiratory morbidity and need for mechanical ventilation. We planned to perform subgroup analyses for the primary outcomes according to gestational age at randomisation and type of corticosteroid (betamethasone or dexamethasone). We also planned to perform sensitivity analysis, including only studies at low risk of bias.

Main results: We included one trial in which participants were randomised to receive either betamethasone or usual care. The trial included 942 women and 942 neonates recruited from 10 UK hospitals between 1995 and 2002. This review includes only trials that met predefined criteria for trustworthiness. We removed three trials from the analysis that were included in the previous version of this review. The risk of bias was low for random sequence generation, allocation concealment and incomplete outcome data. The risk of bias for selective outcome reporting was unclear because there was no published trial protocol, and therefore it is unclear whether all the planned outcomes were reported in full. Due to a lack of blinding we judged there to be high risk of performance bias and detection bias. We downgraded the certainty of the evidence because of concerns about risk of bias and because of imprecision due to low event rates and wide 95% confidence intervals (CIs), which are consistent with possible benefit and possible harm Compared with usual care, it is uncertain if antenatal corticosteroids reduce the risk of RDS (relative risk (RR) 0.34 95% CI 0.07 to 1.65; 1 study; 942 infants) or TTN (RR 0.52, 95% CI 0.25 to 1.11; 1 study; 938 infants) because the certainty of evidence is low and the 95% CIs are consistent with possible benefit and possible harm. Antenatal corticosteroids probably reduce the risk of admission to neonatal special care for respiratory complications, compared with usual care (RR 0.45, 95% CI 0.22 to 0.90; 1 study; 942 infants; moderate-certainty evidence). The proportion of infants admitted to neonatal special care for respiratory morbidity after treatment with antenatal corticosteroids was 2.3% compared with 5.1% in the usual care group. It is uncertain if antenatal steroids have any effect on the risk of needing mechanical ventilation, compared with usual care (RR 4.07, 95% CI 0.46 to 36.27; 1 study; 942 infants; very low-certainty evidence). The effect of antenatal corticosteroids on the maternal development of postpartum infection/pyrexia in the first 72 hours is unclear due to the very low certainty of the evidence; one study (942 women) reported zero cases. The included studies did not report any data for neonatal hypoglycaemia or maternal mortality/severe mortality.

Authors' conclusions: Evidence from one randomised controlled trial suggests that prophylactic corticosteroids before elective caesarean section at term probably reduces admission to the neonatal intensive care unit for respiratory morbidity. It is uncertain if administration of antenatal corticosteroids reduces the rates of respiratory distress syndrome (RDS) or transient tachypnoea of the neonate (TTN). The overall certainty of the evidence for the primary outcomes was found to be low or very low, apart from the outcome of admission to neonatal special care (all levels) for respiratory morbidity, for which the evidence was of moderate certainty. Therefore, there is currently insufficient data to draw any firm conclusions. More evidence is needed to investigate the effect of prophylactic antenatal corticosteroids on the incidence of recognised respiratory morbidity such as RDS. Any future trials should assess the balance between respiratory benefit and potential immediate adverse effects (e.g. hypoglycaemia) and long-term adverse effects (e.g. academic performance) for the infant. There is very limited information on maternal health outcomes to provide any assurances that corticosteroids do not pose any increased risk of harm to the mother. Further research should consider investigating the effectiveness of antenatal steroids at different gestational ages prior to caesarean section. There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review.

Trial registration: ClinicalTrials.gov NCT00139256 NCT01772381.

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Conflict of interest statement

Alexandros Sotiriadis: I am Associate Professor of Obstetrics, Gynaecology and Maternal Fetal Medicine at Aristotle University of Thessaloniki, Greece. I am also a private practicing physician at EMVRYO PCC.

George Makrydimas: none known.

Stefania Papatheodorou: none known.

John PA Ioannidis: none known.

Emma McGoldrick: I am an author of another Cochrane Review entitled 'Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth' (McGoldrick 2020). I am also an author on an overview relating to antenatal corticosteroids (McGoldrick 2016). The present review is potentially eligible for inclusion in the overview. I will not be involved in any assessment or data extraction and two independent review authors will assess this review.

Roses Parker: none known.

Fiona Stewart: I am an author of the Cochrane Review entitled 'Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth' (McGoldrick 2020).

Figures

1
1
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2
Study flow diagram
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 1: Respiratory distress syndrome
1.2
1.2. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 2: Transient tachypnoea of the neonate
1.3
1.3. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 3: Admission to neonatal special care (all levels) for respiratory morbidity
1.4
1.4. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 4: Admission to neonatal intensive care unit for respiratory morbidity
1.5
1.5. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 5: Need for mechanical ventilation
1.6
1.6. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 6: Maternal development of postpartum infection
1.7
1.7. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 7: Admission to neonatal special care (all levels) for any indication
1.8
1.8. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 8: Neonatal infectious morbidity
1.9
1.9. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 9: Perinatal death
1.10
1.10. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 10: Length of stay in neonatal intensive care unit (days)
1.11
1.11. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 11: Readmission for respiratory problems after initial discharge
1.12
1.12. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 12: Cognitive impairment
1.13
1.13. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 13: Emotional and behavioural problems: measured with Strengths and difficulties questionnaire
1.14
1.14. Analysis
Comparison 1: Antenatal corticosteroids (betamethasone) versus usual care, Outcome 14: Adverse maternal effects of therapy
See this image and copyright information in PMC

Update of

References

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References to other published versions of this review

Sotiriadis 2007
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