McKinlay et al reported that repeat doses of antenatal corticosteroids (ACS) should be considered in women at risk of preterm birth in 7 days or longer in view of the neonatal benefits. This statement and effects on other neonatal outcomes need comment.

First, pooled results from 8 trials showed that treatment with repeat dose(s) reduced the risk of respiratory distress syndrome (risk ratio, 0.83; 95% confidence interval, 0.75–0.91). According to the authors, the direction of treatment effect favored repeat dose(s) in all but 1 trial. But if we carefully look at 8 trials, 5 trials did not favor repeat doses(s). In the remaining 3 trials favoring repeat doses(s), 1 trial was a small pilot study, and in another trial, 36% of the infants were born after 34 weeks (outcome would be favorable even after 1 dose, although many doses might have been given if corticosteroids were started at much earlier gestation). It would have been better if the authors had shown the forest plot, and the funnel plot could also have been plotted to show any bias. Another important point is that among 5 trials reporting the effect of repeat dose(s) on the risk of severe respiratory distress syndrome, the reduction of risk was found in 1 trial only.

Second, pooled results from 7 trials showed that infants exposed to repeat dose(s) had a reduced risk of combined serious outcome (risk ratio, 0.84; 95% confidence interval, 0.75–0.94). One included trial did not report this outcome. Of the remaining 6 trials, 3 trials did not favor repeat dose(s), and among the other 3 trials favoring repeat dose(s), 1 was a small pilot study. As mentioned in the earlier text, both the forest plot and the funnel plot could have been constructed for this outcome also.

Table 4 showed no difference in the neurodevelopmental outcomes. But the doses used were different. One trial used a single repeat dose and found no difference, whereas the others used multiple dose(s). Among the latter, 1 study reported a higher rate of cerebral palsy in the repeat-course than in the single-course group (2.9% vs 0.5%, P = .12). Although this finding did not attain statistical significance, there is a possibility that this could be statistically significant in a larger trial. In addition to this factor, the total dose(s) and number of courses also differed (Maternal-Fetal Medicine Network study, 24 mg vs Australasian Collaborative Trial of Repeat Doses of Steroids study, 11.4 mg). In the Maternal-Fetal Medicine Network study, 5 of 6 infants with cerebral palsy were exposed to 4 or more courses. In the Australasian Collaborative Trial of Repeat Doses of Steroids study, the repeat-dose(s) group was more likely to warrant assessment for attention problems ( P = .04).