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Meta-Analysis
. 2018 Aug 3;8(8):CD006614.
doi: 10.1002/14651858.CD006614.pub3.

Corticosteroids for preventing neonatal respiratory morbidity after elective caesarean section at term

Alexandros Sotiriadis  1 , George Makrydimas, Stefania Papatheodorou, John Pa Ioannidis, Emma McGoldrick
Affiliations
Meta-Analysis

Corticosteroids for preventing neonatal respiratory morbidity after elective caesarean section at term

Alexandros Sotiriadis et al. Cochrane Database Syst Rev. .

Update in

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.

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 management without corticosteroids, in reducing neonatal respiratory morbidity and admission to special care with respiratory complications.

Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 June 2017), and reference lists of retrieved studies.

Selection criteria: 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).

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

Main results: We included four trials (3956 women and 3893 neonates) at a moderate risk of bias, comparing prophylactic administration of betamethasone or dexamethasone versus placebo or usual treatment without steroids in term elective caesarean section. Women randomised to treatment group received either two intramuscular doses of betamethasone in the 48 hours before delivery, or intramuscular dexamethasone (two or four doses) prior to delivery (at 37 weeks' gestation or 48 hours before delivery), and were compared to the control group who received a saline placebo or treatment as usual.Prophylactic antenatal corticosteroid administration appeared to decrease the risk of respiratory distress syndrome (RDS) (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.87; 4 studies; 3817 participants; low-quality evidence), transient tachypnoea of the neonate (TTN) (RR 0.43; 95% CI 0.29 to 0.65; 4 studies; 3821 participants; low-quality evidence), admission to the neonatal intensive care unit (NICU) for respiratory morbidity (RR 0.42; 95% CI 0.22 to 0.79; 3 studies; 3441 participants), and admission to neonatal special care (all levels) for respiratory complications (RR 0.45; 95% CI 0.22 to 0.90; 1 study; 942 participants; low-quality evidence). Administration of antenatal corticosteroids also appeared to reduce admission to neonatal special care (RR 0.62; 95% CI 0.43 to 0.89; 2 studies; 2169 participants) and neonatal intensive care (RR 0.14; 95% CI 0.03 to 0.61; 1 study; 452 participants) for any indication, compared to placebo or usual care. Finally, prophylactic antenatal corticosteroids also appeared to reduce the length of stay in NICU by 2.70 days (mean difference (MD) -2.70; 95% CI -2.76 to -2.64; 2 studies; 32 participants).No reduction was found in the need for mechanical ventilation (RR 0.67; 95% CI 0.27 to 1.68; 3 studies; 3441 participants; very-low quality), perinatal death (RR 0.67; 95% CI 0.11 to 4.10; 4 studies; 3893 participants) or neonatal sepsis (RR 1.00; 95% CI 0.06 to 15.95; 2 studies; 2214 participants) .There were no reported events of neonatal respiratory complications (other than RDS and tachypnoea of the newborn (TTN)), chronic lung disease, duration of mechanical ventilation or maternal postpartum infection, therefore results on these outcomes are non-estimable. The studies did not provide data on other pre-defined outcomes.The quality of evidence, as assessed using GRADE was low for the outcomes of RDS, TTN and admission to NICU for respiratory morbidity, indicating that the true effect could potentially be substantially different from our estimate of effect.

Authors' conclusions: The results from the four trials are promising, but more high-quality studies with larger sample sizes that are adequately powered to detect the effect of prophylactic antenatal corticosteroids on outcomes of respiratory morbidity are needed, given the potential of the current studies for bias. Consideration should be given to the balance between statistical significance and clinical significance, particularly in view of the low event rates of significant respiratory morbidity (RDS or admission to NICU for respiratory complications) in this population. In addition, further trials on the long-term outcomes of these infants are needed to identify any potential harms and complications of antenatal corticosteroid administration at term.

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Conflict of interest statement

Alexandros Sotiriadis: none known.

George Makrydimas: none known.

Stefania Papatheodorou: none known.

John PA Ioannidis: none known.

Emma McGoldrick: I am an author of an overview relating to antenatal corticosteroids (McGoldrick 2016). This 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.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Ahmed 2015 {published data only}
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Nada 2016 {published data only (unpublished sought but not used)}
    1. NCT01772381. Dexamethasone in prevention of respiratory morbidity in elective caesarean. clinicaltrials.gov/show/NCT01772381 (First received: 31 December 2012).
    1. Nada AM, Shafeek MM, Maraghy MA, Nageeb AH, Salaheldine AS, Awad MH. Antenatal corticosteroid administration before elective caesarean section et term to prevent neonatal respiratory morbidity: a randomized controlled trial. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2016;199:88‐91. - PubMed
Nooh 2018 {published data only}
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Stutchfield 2005 {published and unpublished data}
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References to studies excluded from this review

Christofori 2011 {published data only}
    1. Christofori G. Antenatal corticosteroids and respiratory distress syndrome in late preterm infants born by elective cesarean section. Multicentric randomized controlled clinical trial. clinicaltrialsregister.eu/ctr‐search/trial/2011‐002919‐28/IT (first received: 5 December 2011).
Jain 2005 {published data only}
    1. NCT00139256. Randomized controlled trial of antepartum betamethasone treatment for prevention of respiratory distress in infants born by elective cesarean section. clinicaltrials.gov/show/NCT00139256 (first received 29 August 2005).
Langer 2008 {unpublished data only}
    1. NCT00446953. Caesarean and corticotherapy. clinicaltrials.gov/show/NCT00446953 (first received: 12 March 2007.
Sananes 2017 {published data only}
    1. Sananes N, Koch A, Escande B, Aissi G, Fritz G, Roth E, et al. Pilot randomised controlled trial comparing the risk of neonatal respiratory distress in elective caesarean section at 38 weeks' gestation following a course of corticosteroids versus caesarean at 39 weeks. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2017;212:54‐9. - PubMed

References to studies awaiting assessment

Ammar 2013 {published data only}
    1. Ammar AR, Rabei NH, Gad HA. Dexamethasone in prevention of respiratory morbidity in elective cesarean section in term fetus. A randomized controlled trial. Journal of American Science 2013;9(6):286‐9.

References to ongoing studies

Ahmadpour‐kacho 2015 {unpublished data only}
    1. IRCT2015090923963N1. Effect of antenatal steroid before elective cesarean section(c/s) on prevention of respiratory morbidity of term neonates. en.search.irct.ir/view/25584 (first received: 13 November 2015).
Custo 2007 {unpublished data only}
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