What is the issue?
Babies born at term (at or after 37 weeks of pregnancy) by planned (elective) caesarean section, before onset of labour, are more likely to develop breathing complications than babies born vaginally. Giving injections called corticosteroids to the mother has been shown to reduce the risk of breathing problems in babies born before 34 weeks of pregnancy, but it is not clear if they are also useful for babies born by caesarean section at term.
Why is this important?
Caesarean section increases the risk of a term newborn developing breathing problems, such as rapid breathing over the first few days (known as transient tachypnoea of the neonate) and the more serious respiratory distress syndrome (RDS). The affected babies may need treatment in special care units. This risk decreases from 37 weeks to 39 weeks of gestation, at which stage it is low. Most caesarean sections are performed after 39 weeks of gestation, but there are some instances when babies need to be born earlier. The aim of this review was to investigate if corticosteroids can reduce the rates of breathing problems prior to caesarean section, without causing problems for the mother or the infant.
How did we identify and evaluate the evidence?
We searched the medical literature for randomised controlled studies that met our criteria for being trustworthy and compared the effects of corticosteroids against a placebo (dummy) treatment or against usual care. We rated our confidence in the findings based on factors such as the number of studies, study methods, number of women and babies involved, the number of events and the variability of the findings.
What evidence did we find?
We included evidence up until 20 January 2021. We included one trial that involved 942 women and 942 babies recruited from 10 UK hospitals. The women in the treatment group received two doses of the corticosteroid betamethasone by injection into the muscle. The women in the control group received usual care. No blinding procedures were used therefore all the women, caregivers and investigators were aware of who received corticosteroids and who received usual care.
It is uncertain if corticosteroids reduce the risk of transient tachypnoea of the neonate (a mild breathing problem) or respiratory distress syndrome (i.e serious breathing problems) compared with usual care. Antenatal corticosteroids probably reduce the risk of admission to neonatal special care for breathing complications compared with usual care.
It is uncertain if corticosteroids have any effect on the risk of the baby needing additional breathing support (mechanical ventilation) compared with usual care. It is uncertain if antenatal corticosteroids have any effect on women developing infection or high temperature within 72 hours of giving birth (there were no cases in the one study involving 942 women).
We did not find any evidence about the baby's risk of low blood sugar or about the woman's risk of serious illness, death or wound infection.
Certainty of evidence
The certainty of evidence from the included randomised trial was very low to moderate. This means that we can not be completely confident that future trials will come to the same conclusions about the treatment benefits for the babies of mothers receiving a course of antenatal corticosteroids prior to caesarean section at term.
What does this mean?
The risk of being admitted to neonatal special care because of breathing problems was reduced in one study. It is uncertain if corticosteroids have any effect on the risk of serious breathing problems (respiratory distress syndrome) or rapid breathing (transient tachypnoea) in the neonate, compared with usual care. Further studies are needed to investigate if antenatal corticosteroids do reduce the risk of serious respiratory problems (such as respiratory distress syndrome). Future trials need to make sure they assess for possible short- and long-term harm to both mother and baby after receiving a course of antenatal corticosteroids prior to caesarean section at term. Further research could consider assessing whether any benefits or harms identified by giving a course of antenatal corticosteroids are affected by the gestational age at which the planned caesarean is performed.
There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review.
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.
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.
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.
For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov (20 January 2021) and reference lists of retrieved studies.
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.
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.
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 morbidity.