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The role of prenatal steroids at 34–36 weeks of gestation
  1. Gordon CS Smith1⇑,
  2. David Rowitch2,
  3. Ben WJ Mol3
  1. 1 Department of Obstetrics and Gynaecology, Cambridge University, Cambridge, UK
  2. 2 Department of Paediatrics, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge, UK
  3. 3 Department of Obstetrics and Gynaecology, The Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, Australia
  1. Correspondence to Professor Gordon CS Smith, Department of Obstetrics and Gynaecology, University of Cambridge, NIHR Cambridge Comprehensive Biomedical Research Centre, Box 223, The Rosie Hospital, Cambridge CB2 2SW, UK; gcss2{at}cam.ac.uk

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A recent multicentre, double-blind, randomised, placebo-controlled trial has demonstrated that administration of betamethasone to women with threatened preterm delivery at 34–36 weeks of gestational age reduces the risk of neonatal respiratory morbidity. There is, however, no long-term outcome data on the children, and we believe that it is biologically plausible that this treatment may cause long-term harm through effects on the infant’s brain. Given this, we argue that steroids should not be used in the context of late preterm delivery until evidence of long-term safety is available. This example illustrates some strengths and weaknesses of using ‘levels of evidence’ to grade the empirical support for making clinical decisions.

One of the major advances in perinatal medicine in the last 30 years has been the administration of synthetic glucocorticoids to mothers who are likely to deliver at extreme preterm gestational ages, and this intervention clearly reduces perinatal mortality and severe morbidity.1 A recent multicentre, double-blind, randomised controlled trial (RCT) compared the effects of betamethasone versus placebo among women presenting between 34 and 36 weeks of gestational age with a high probability of delivery.2 The primary outcome was need for respiratory support 3 days after delivery. The rate was 11.6% in steroid-treated children and 14.4% with placebo, yielding a number needed to treat of 35 (95% CI 19 to 259). In addressing the question of whether this trial justifies immediate incorporation of glucocorticoids into the management of threatened delivery at 34–36 weeks, we need to consider both the science of glucocorticoids in pregnancy and the science of clinical trials.

Physiologically, the fetus prepares for birth near term by an increased production of cortisol from the fetal adrenal. The glucocorticoids employed therapeutically to accelerate fetal lung maturation are betamethasone and dexamethasone. The choice is purposeful as both are resistant to 11β-hydroxysteroid dehydrogenase-2 …

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