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Re: Single versus multiple courses of antenatal steroids - uncertainty remains

Whitelaw and Thoresen recently reviewed the current evidence concerning the effects of antenatal steroids on brain development, and made suggestions for clinical practice.

We believe that interpretation of current evidence is not yet clear enough to determine clinical practice, and further research is necessary before such recommendations are possible. No randomised controlled trials comparing single with multiple courses of corticosteroids have been completed, and current evidence is from observational studies of humans and animal experiments. There are several problems with interpretation of these results.

Firstly, animal experiments have demonstrated impaired growth of the brain after antenatal exposure to corticosteroids, but it is not known to what extent similar changes may occur in human brains, nor whether they lead to functional problems. Secondly, observational studies may suffer from several sources of bias; for example, infants exposed to single and multiple courses of antenatal steroids may be born at different gestational ages, may be born to mothers suffering from different conditions, or may be exposed to a high-risk situation for different amounts of time. These biases could influence the results of observational studies in either direction. Finally, publication bias may have influenced the available evidence; papers suggesting harmful effects from multiple courses of steroids may have been more readily published during recent years than those showing no effect or benefit. No firm conclusions can be drawn from the available evidence and we cannot say whether multiple courses of antenatal steroids are beneficial, harmful or have no effect.

Better evidence is needed to resolve this issue, and several large randomised controlled trials comparing single and multiple courses of antenatal steroids are either planned or in progress around the world. Until these trials are completed the uncertainty about the risks and benefits of multiple courses of antenatal steroids must remain. The best policy for obstetricians would therefore be to take part in the current trials in order to resolve this issue as quickly as possible.

In the UK the TEAMS trial is currently recruiting, and more centres are needed. The study can be contacted by telephone (+44 (0) 1865 227122), or email (teams@perinat.ox.ac.uk).

Simon Gates
Peter Brocklehurst
Ann Johnson
National Perinatal Epidemiology Unit
Institute of Health Sciences
Old Road, Oxford OX3 7LF, UK

Zarko Alfirevic
Department of Obstetrics and Gynaecology
Liverpool Women's Hospital
Crown Street, Liverpool L8 7SS, UK