Outcomes at 2 years of age after repeat doses of antenatal corticosteroids

Preterm birth is a major risk factor for neurosensory impairments and disabilities, such as cerebral palsy. It has been demonstrated that a single course of antenatal corticosteroids given to women at risk for preterm delivery could reduce neonatal mortality and morbidity and the incidence of long-term neurologic sequelae. However, infants born more than 7 days after exposure to a single course of antenatal corticosteroids have lower birth weight and increased mortality than unexposed infants. Therefore, antenatal corticosteroids administration is often repeated after 7 or more days, even if this therapeutic strategy is at present not fully supported by clinical and experimental evidence. In fact, exposure to repeat courses of corticosteroids has been associated with poorer infant growth and abnormal development. However, not all observational studies have shown an increased incidence of neurosensory disability after repeat doses of corticosteroids; it is interesting to notice that one study suggested a reduction in the incidence of cerebral palsy. Moreover, short-term results of the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS), during which women were randomized to weekly injection of betamethasone or placebo, showed that repeated administration of corticosteroids is associated to a lower incidence of respiratory distress syndrome, severe neonatal lung disease, and serious neonatal morbidity than single course. However, data have not been available regarding longer-term effects of this treatment.

On these bases, outcomes at 2 years of corrected age of surviving children whose mothers took part in the ACTORDS trial were monitored, in order to assess if exposure to repeat doses of antenatal corticosteroids might affect the rate of survival free of major neurosensory disability and psychophysical  development.

Of the 1085 children who were alive at 2 years of age, 1047 (96.5%) were seen for assessment (521 exposed to repeat-corticosteroid treatment and 526 exposed to placebo). The rate of survival free of major disability was similar in the repeat corticosteroid and placebo groups (84.4% vs 81.0%). There were no significant differences between the groups in body size, blood pressure, use of health services, respiratory morbidity, or child behavior scores, although children exposed to repeat doses of corticosteroids were more likely than those exposed to placebo to warrant assessment for attention problems (P = 0.04).

It has been previously demonstrated that exposure to one or more repeat doses of antenatal betamethasone could reduce the risk of respiratory distress syndrome and overall serious neonatal morbidity. Results of the current report show that this treatment does not change survival free of major neurosensory disability or growth to 2 years of age. According to these results, clinicians may decide to consider the use of a single injection of betamethasone, or equivalently, repeat the administration weekly if the woman remains at risk for very preterm delivery, 7 or more days after an initial course of antenatal corticosteroids.

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