Decline in effectiveness of antenatal corticosteroids with time to birth: real or artefact?

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Simon Gates, principal research fellow1,
Peter Brocklehurst, director2

¹Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry CV4 7AL
²National Perinatal Epidemiology Unit, University of Oxford, Oxford OX3 7LF

Correspondence to: S Gates s.gates{at}warwick.ac.uk

Accepted 6 May 2007

The widely accepted notion that the benefits of antenatal corticosteroids decline with time to birth may not be correct, argue Simon Gates and Peter Brocklehurst, as the evidence is based on unsound subgroup analyses

The effectiveness of antenatal corticosteroids to prevent neonatal lung disease in women at risk of preterm birth was established by systematic reviews. In addition, subgroup analyses suggested that treatment was most effective in babies born one to seven days after administration. This belief led to widespread use of repeated courses of corticosteroids in women who did not deliver within a week or two of initial treatment. However, the notion that effectiveness declines after seven days may be incorrect, as the analyses that it is based on are unreliable. Here, we discuss the methodological problems of these analyses and their relevance to current randomised controlled trials of repeated versus single courses.

So, what is the evidence?

Babies born before 32 weeks' gestation often have neonatal lung disease, a major cause of neonatal mortality and morbidity—the earlier the birth, the greater the risk. Corticosteroids given to mothers at risk of preterm delivery accelerate fetal lung development, and the effectiveness of this treatment for preventing neonatal lung disease was investigated in a series of randomised controlled trials from the 1970s onwards. Some trials showed a significant benefit of antenatal corticosteroids, but some showed no significant effect. A landmark systematic review1 2 3 resolved the apparent discrepancies in the results and established that this treatment reduced death and respiratory distress syndrome in the babies of these women. A forest plot from this review is used in the Cochrane Collaboration's logo, and the intervention is now used routinely in clinical practice.

Another clinically important question is whether (and how) the effectiveness of antenatal corticosteroids changes with time after administration. This question was investigated by …