We are pleased that our paper on the use of repeated courses of corticosteroids in the UK has stimulated further discussion as this is obviously an important topic for current obstetric practice. We agree with Spencer and Pakarian that adverse effects have been reported in babies whose mothers have received multiple courses of corticosteroids. The evidence, however, both from animal and human studies is conflicting. Some reports suggest a decreased incidence of adverse neonatal outcomes and others suggest harmful effects1–3. One reason for this is that observational studies are unable to separate the effect of multiple courses from either the influence of different gestational ages at delivery or the disorder for which multiple courses were prescribed. As the authors point out, women who received multiple courses of steroids are more likely to be delivered at later gestations when risk of neonatal respiratory distress and other premature complications are uncommon. However, it can also be argued that women who receive multiple courses of corticosteroids remain in an at-risk situation for longer and this in itself may be associated with a worse perinatal outcome. Without a randomised controlled trial the relative contribution of these two biases cannot be known.
As our survey of practice showed, 98% of units that responded to the survey in the UK currently prescribe multiple courses of corticosteroids to some women. Whether this confers benefit, causes harm or has no effect on the condition of these babies is currently unknown and unlike Spencer and Pakarian we argue that not to do a randomised controlled trial is unethical. While waiting for the results of this trial it is not possible to recommend the number of courses of corticosteroids that may or may not be beneficial or harmful. This information can only come from a well-designed randomised controlled trial. There is no other methodology which can produce a bias-free answer.
Finally Spencer and Pakarian are concerned that a trial of the duration of the efficacy of antenatal corticosteroids may be confounded by increasing gestation. The trial that we are proposing and which started in November 1999, recruits women who have already received a single course of corticosteroids because of the risk of preterm delivery. They are then randomised to receive further courses of corticosteroids or placebo for as long as the clinician feels is necessary which will depend, to an extent, on the duration of the risk factor. As a consequence, the two groups will be delivered at similar times. We are confident that we can compare the results of the two groups and explore the potential for benefit or harm with two, three, four or more courses of corticosteroids to determine whether a dose response effect exists. Further information about the trial including the full protocol can be obtained on the National Perinatal Epidemiology Unit web site at http://www.npeu.ox.ac.uk/trials/protocol/index.html.