Objective: To determine the effects of multiple courses of maternal betamethasone for fetal lung maturation on neonatal serum cortisol levels and clinical Cushing syndrome.
Methods: Seventy-nine mother-infant pairs delivered between 24 and 36 weeks' gestation were enrolled in the study. They were grouped according to the number of courses of betamethasone received between 24 and 34 weeks' gestation for fetal lung maturation: those receiving no courses, one course, and two or more courses. Physical examinations were performed and serum glucose, electrolyte, and cortisol levels were measured on days 1 and 3 of life.
Results: For those receiving multiple courses of betamethasone (n = 43), the mean (+/- standard error of the mean [SEM]) number of courses was 5.3 +/- 0.4, with a mean (+/-SEM) total dose of 125.0 +/- 10.7 mg. No neonates had findings suggestive of Cushing syndrome. Day 1 cortisol levels (pooled mean +/- SEM) were 12.6 +/- 2.4, 5.3 +/- 3.2, and 4.4 +/- 1.8 microg/dL in those receiving no courses, one course, and two or more courses, respectively (P = .03; no courses versus two or more courses, P = .03), but the differences were not significant when corrected for multiple variables. Differences among day 3 cortisol levels (pooled mean +/- SEM) were not significant: 8.3 +/- 1.6, 5.8 +/- 1.4, and 5.8 +/- 0.9 microg/dL in those receiving no courses, one course, and two or more courses, respectively. None of the neonates in the group receiving no courses of betamethasone had day 1 cortisol levels lower than normal, whereas 22% and 11% of the neonates receiving one and two or more courses, respectively, had day 1 levels lower than normal. On day 3, 15% of those receiving one course and 10% of those receiving two or more courses had serum cortisol levels lower than normal, whereas none of those who received no courses had a low cortisol level. Multivariate regression analysis could show no association between the number of courses or total dose of betamethasone and the day 1 or day 3 cortisol values. The day 1 cortisol level (log10) was most associated with the severity of respiratory distress syndrome (RDS) and day 3 cortisol level (log10) with race and severity of RDS. Only in neonates with absent or mild RDS did number of courses correlate with day 3 cortisol levels (log10), but this was a positive correlation.
Conclusion: Serum cortisol levels either were independent of the number of courses or total dose of corticosteroids given or, in a subpopulation, were associated with increasing levels with increasing doses, suggesting that there is no suppressive effect with repeated dosing.