Multiple courses of antenatal corticosteroids

In this comment, published on Lancet, John Newnham (University of Western Australia, Perth) and Karen Simmer (King Edward and Princess Margaret Hospitals, Perth) address the issue of repeated antenatal corticosteroid administration. In fact, after more than three decades of use of this treatment to enhance fetal maturation before preterm birth, it seems that the risk of repeated administration might overcome the benefits. In fact, experimental studies suggested that multiple exposures to corticosteroids can affect the development of many organs, including the brain. In humans, three or more courses of antenatal corticosteroids were associated with behavioural problems in early age.
This observation is strengthened by the results of the MACS trial, by Murphy and colleagues, recently published in The Lancet. This international multicentre study included pregnant women at risk of preterm birth who had received a single course of antenatal corticosteroids 14-21 days previously. These patients were randomized to receive multiple courses every 14 days, or placebo. Results showed no improvements in outcome in the babies who had received the extra courses of antenatal corticosteroids. However, growth was affected, with significant reductions at birth in weight, length, and head circumference. The investigators concluded that multiple courses of antenatal corticosteroids every 14 days are not recommended. These observations confirm what reported in other trials, suggesting that repeated administration of corticosteroids is not associated to additional benefits.
The publication of MACS trial, the largest to date, is an important milestone in the knowledge and in the use of antenatal corticosteroids. In fact, the follow-up of the children included in the MACS will likely provide major insights into the possible long-term adverse effects of repeated antenatal corticosteroids. In particular, attention should be given to different areas, such as behaviour, growth, glucose tolerance, and blood pressure, according to the suggestions of previous studies. Taken together, current evidences recommend that repeated injections of antenatal corticosteroids should not be prescribed, while single-course therapy is of considerable benefit.

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