Antenatal steroids for preterm labor, a revolutionary low cost invervention in perinatology, is responsible for improving the neonatal survival and reducing severity of respiratory distress syndrome (RDS) in preterm babies(1). The current recommendations originate from the 1994 National Institute of Health (NIH) Consensus Conference and reinforced by a second NIH Consensus Conference in 2000(2). One of the key points from the guidelines mention repeated courses of corticosteroids may not be safe and should not be administered outside of clinical trials.

After one course (total of 24 mg of Betamethasone or Dexamethasone, given over 24 or 48 hours respectively) of antenatal steroid, the maximum benefits are seen if the fetus is delivered 24 hours after and within 7 days of the last dose(1). Because the beneficial effects wanes off after 7 days, it is conjectured, there might be benefit from repeated courses of antenatal steroids. However, concerns have been raised about the safety of multiple courses of antenatal steroids. The study by Mazumder, et al. again cautions about the use of multiple courses(3). The authors did not find any beneficial effect on the immediate neonatal morbidity including severe RDS. Though not adequately powered to detect the major difference, the findings are in accordance with the recent National Institute of Child Health (NICHD) trial which failed to show an effect on the primary composite outcome of severe respiratory distress syndrome, grade III or IV intraventricular hemorrhage, chronic lung disease or periventricular leukomalacia. However, repeat doses did result in better lung function as compared to single course in infants delivered below 32 weeks of gestation(4). Another trial performed in Australia and New Zealand, Australian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) demonstrated significant reduction in the rates of respiratory distress syndrome or severe lung disease(5). Even the Cochrane review concluded that there is a short term beneficial effect of multiple courses of antenatal corticosteroids on respiratory distress syndrome as compared with those given a single course (26 % vs 32 %, RR 0.82; 95 CI 0.72.0.93; four trials, 2155 women)(6).

Another significant finding of the study were the effect on anthropometeric parameters at 6 months of age. Other studies have found detrimental effects on the head circumference and weight at birth but not at 40 weeks of corrected age(5). Though there are some methodological issues in the current study (unacceptably high lost to follow up rates and some babies still to be accessed at six months), the effect on anthropometry highlights another potential harm of such an intervention. The study, though underpowered, is yet to report the results of neurodevelopmental outcome at 18 months of age. It has to be noted that ACTORDS study did not find any change in either survival free major neuro-sensory disability or body size at 2 years of age(7), On the contrary, the NICHD study reported trends towards higher rate of cerebral palsy among children at 2-3 years of age who have been exposed to repeat courses of corticosteroids(8). Even animal studies have shown delayed myelination and decreased growth of all areas of the fetal brain, especially the hippocampus, following repeated antenatal steroid use(9,10).

To conclude, though repeat dosing of antenatal corticosteroids could improve the immediate out-comes after preterm birth, given the evidence of potential adverse effects it is recommended that only a single course be used in clinical practice until results of more robust randomized controlled trials with neuromotor outcomes are available. The current data argue against the weekly administration of antenatal corticosteroids.

Funding: None.

Competing interests: None stated