Evidence
Alert

A dose of corticosteroids benefits most women anticipating a preterm delivery

Giving corticosteroids to most women who are anticipating labour before completing 37 weeks of pregnancy helps reduce immediate health problems in the baby compared with placebo or no intervention. Deaths around the time of birth were reduced by 28% and babies were a third (34%) less likely to develop respiratory distress syndrome.

A corticosteroid dose is already used for women who go into labour or if waters break before 37 weeks or where delivery is planned for other reasons. The drug accelerates the development of the baby’s lungs and reduces breathing difficulties at birth. This recommendation followed decades of research.

This review supports current practice of using a dose of corticosteroids in high-income settings and was designed to include more recent research and to look in more depth at new questions, such as the risk of infection. Evidence is still lacking in low-income settings and some very high-risk groups, like twins. There is also remaining uncertainty about the best corticosteroid, its dose and timing.

Why was this study needed?

About one in every 13 babies in the UK is preterm, which means born before 37 weeks of pregnancy. Preterm babies are at higher risk for complications due to a lack of full development of several organs. This can lead to disability and death. Breathing difficulties such as respiratory distress syndrome are among preterm babies’ serious complications.

The benefits of corticosteroids in prevention of respiratory distress syndrome has been investigated since 1972. A recent review found that corticosteroids in late preterm babies, at 34 to 37 weeks of pregnancy, reduce the risk of respiratory distress syndrome.

This review and meta-analyses focuses on the use of corticosteroids in women at risk of preterm birth from 24 weeks. The authors aimed to include findings from new trials, to summarise the impact of corticosteroids on new outcomes such as infections and to define needs for future research.

What did this study do?

This systematic review compared the use of corticosteroids with placebo or no intervention in women at 24 to 37 weeks pregnancy at risk of birth. It included 30 randomised controlled trials with a total of 7774 women and 8158 babies. Nine new trials were added since the previous review in 2006.  The drugs used were betamethasone, dexamethasone or hydrocortisone. Most women received a single dose of corticosteroid, and in nine studies women received weekly doses.

The main outcomes for babies included respiratory distress syndrome, bleeding in the brain, perinatal death (stillbirth or death within the first week) and neonatal death (within the first 28 days of life).

A bias present in the conduction of some studies where participants and health professionals were aware of whether the intervention was given or not is unlikely to have affected confidence in the results. Outcome assessment was blinded. All studies except one were conducted in high-income countries.

What did it find?

  • Antenatal corticosteroids reduced respiratory distress syndrome by 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.56 to 0.77). Specifically, the risk reduced from 17.6% to 11.6% (95% CI 9.8% to 13.5%). Six studies looked into moderate/severe respiratory difficulties and showed similar findings (RR 0.59, 95% CI 0.38 to 0.91).
  • Based on 15 studies and 6729 participants, corticosteroids reduced perinatal death rate from 10.2% to 7.3% (RR 0.72, 95% CI 0.58 to 0.89).
  • Corticosteroids also reduced neonatal deaths (RR 0.69, 95% CI 0.59 to 0.81) and necrotising enterocolitis - severe inflammation of the intestines (RR 0.50, 95% CI 0.32 to 0.78).
  • Corticosteroids had no effect on maternal death (RR 0.98, 95% CI 0.06 to 15.50). This result was based on few events (one trial with two deaths, four trials with no deaths).

What does current guidance say on this issue?

The NICE 2015 guideline on preterm labour and birth recommends offering corticosteroids between 26 and 33 weeks plus six days of pregnancy to women who are in suspected, diagnosed or established preterm labour, are having a planned preterm birth or have ruptured membranes. It recommends considering corticosteroids for women in the same situation between 23 to 25 weeks plus six days and 34 to 35 weeks plus six days.

The Royal College of Obstetricians and Gynaecologists has a more detailed guideline on antenatal corticosteroids issued in 2010.

What are the implications?

The findings of this study support the practice of giving corticosteroids to women at risk of labour, which became mainstream advice by 2000.

The authors note a need to improve other aspects the antenatal corticosteroid practice and research. Evidence is lacking in low-income settings, multiple pregnancies and high-risk groups, such as women with high blood pressure or ruptured membranes.

It is also important to determine the optimal corticosteroid, dose-to-delivery interval and long-term effects into adulthood.

The advice to use steroids for most women where preterm delivery is anticipated seems secure, without further research.

 

Citation and Funding

Roberts D, Brown J, Medley N, et al. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3:CD004454.

This project was funded by the National Institute for Health Research, via Cochrane Infrastructure funding to Cochrane Pregnancy and Childbirth.

 

Bibliography

Dickson MJ. Why did it take so long for antenatal steroid use to become mainstream. BMJ. 2017.

NHS Choices. Premature labour and birth. London: Department of Health; 2015.

NIHR DC. Antenatal corticosteroids reduce breathing problems in late preterm babies. National Institute for Health Research Dissemination Centre. 2017

NICE. Preterm labour and birth. NG25. London: National Institute for Health and Clinical Excellence; 2015.

RCOG. Antenatal corticosteroids to reduce neonatal morbidity and mortality. London: Royal College of Obstetricians and Gynaecologists; 2010.

WHO. Maternal and perinatal health. Geneva: World health Organization; 2017.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

 

Definitions

Participants were women, with a singleton or multiple pregnancies, expected to deliver preterm (before the 37th week of pregnancy) as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or planned preterm delivery.

 

Commentaries

Expert commentary

This is an important reiteration of the benefits of antenatal corticosteroids, for those not old enough to remember the pre-steroid era. However, it should be noted that there is a place for steroids in planned preterm delivery and that there is a gradient of benefit across the gestations, these points are not noted in “main message” of the review.

The conclusion that more research is needed into optimal timing and dosing is welcome, and for the more mature babies for whom the benefit is less, unintended consequences should be studied.

We hope that in future benefits of antenatal magnesium are equally well described.

Dr J M Hawdon, Responsible Officer, Consultant Neonatologist, Royal Free London NHS Foundation Trust