Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing

Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34 weeks' gestation and the risk for neonatal hypoglycemia.

A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34 weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40 mg/dL).

We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14 days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4.

The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.