Repeated corticosteroids in women at risk of very preterm birth

Preterm babies are at high risk of neonatal lung disease and its sequelae. Respiratory distress syndrome (RDS), which results from immature lung development, is the main cause of early neonatal mortality and morbidity. One effective prenatal therapy to reduce the adverse outcomes of preterm birth is a single course of prenatal corticosteroids given to the mother. However, single course prenatal corticosteroids have not been effective in babies born more than seven days after initial treatment and, moreover, were associated to a higher incidence of perinatal death. It has been suggested that repeating the prenatal corticosteroids in women at risk of preterm birth seven or more days after their initial course may lead to significant benefits, but there has been concern that prenatal corticosteroids may be associated to adverse effects, such as infections, suppression of the fetal hypothalamic-pituitary-adrenal axis, and abnormal neurodevelopment. However, other observational studies have not shown any adverse effects on neurosensory disability and one report suggested protection against cerebral palsy. The efficacy and safety of repeat doses of prenatal steroids is therefore uncertain.

An Australian group recently published on the Lancet the results of a study, which was conducted with the aim to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth could reduce neonatal morbidity without harm. In this hospital-based study, 982 women at risk of preterm birth and at less than 32 weeks' gestation, seven or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeated dose of either 11.4 mg betamethasone (as Celestone Chronodose), or placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal RDS, use and duration of oxygen and mechanical ventilation, and morphometric parameters of the baby at birth and hospital discharge.

The results showed that fewer babies exposed to repeated corticosteroids had RDS (33% vs 41%; p=0.01) and severe lung disease (12% vs 20%; p=0.0003) than the ones in the placebo group. Moreover, babies exposed to repeated corticosteroids needed less oxygen therapy (p=0.03) and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups.

This protective effect of corticosteroids might be attributed to improved lung maturation. It can be suggested, for instance, that sustained exposure to corticosteroids could influence biochemical pathways, increasing surfactant turnover and producing the necessary structural changes to lung tissue.

In conclusion, even if long-term results are still lacking, the short-term benefits for the babies, as observed in this study, support the use of repeated doses of corticosteroids in women at risk of very preterm birth seven or more days after an initial course.

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