Long-Term outcomes after repeat doses of antenatal corticosteroids

Administration of corticosteroids to mothers before preterm delivery significantly reduces perinatal morbidity and mortality. It has been suggested that the optimal benefit of antenatal corticosteroid therapy lasts for 7 days, but potential risks of repeating administration 7 days after the previous course are not well defined. Despite this, the use of repeat courses of antenatal corticosteroids has become widespread.

The Maternal–Fetal Medicine Units (MFMU) Network of the National Institute of Child Health and Human Development (NICHD) therefore designed a randomized clinical trial to compare the outcomes of infants whose mothers were treated with weekly corticosteroids with those of infants whose mothers were treated with a single course. It was observed that repeat courses of corticosteroids had no effects on severe respiratory distress syndrome, grade III or IV intraventricular hemorrhage, chronic lung disease, or periventricular leukomalacia, but improved neonatal lung function if compared with single course therapy, particularly among infants delivered before 32 weeks of gestation. Similar results were found in an other trial performed in Australia and New Zealand. However, both trials found a reduction in birth weight in infants exposed to repeat courses.

In this work, the long-term effects of repeat courses of antenatal corticosteroids on patterns of early childhood growth and development in the children enrolled in the MFMU Network trial are reported. In MFMU trial, women at 23 through 31 weeks of gestation who remained pregnant 7 days after an initial course of corticosteroids were randomized to weekly courses of betamethasone or placebo. Long-term outcomes in children born after these treatments were monitored between 2 and 3 years of corrected age. Pre-specified outcomes included scores on the Bayley Scales of Infant Development, anthropometric measurements, and the presence of cerebral palsy.

In total, 556 infants were available for follow-up; 486 children underwent physical examination and 465 underwent Bayley testing. Mean corrected age was 29.3±4.6 months. Overall, no significant differences in Bayley results or anthropometric measurements were identified. However, although statistical significance was not reached, six children (2.9%) in the repeat-corticosteroid group had cerebral palsy versus one child (0.5%) in the placebo group.

In conclusion, children who had been exposed to repeat as compared with single courses of antenatal corticosteroids did not differ significantly in physical or neurocognitive measures. These findings are reassuring in light of the similar results reported in another long–term analysis by Crowther et al. Despite the results of these two studies, caution is still required, in particular for what concerns the higher rate of cerebral palsy among children who had been exposed to repeat doses of corticosteroids. Overall, the present findings indicate no evident long-term benefit and possible harm of repeat antenatal corticosteroids treatment.

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