Time interval from late preterm antenatal corticosteroid administration to delivery and the impact on neonatal outcomes

Abstract

Although administration of antenatal corticosteroids has been shown to decrease neonatal respiratory morbidity when given to women at risk for late preterm birth, the time interval from antenatal corticosteroid administration to delivery that is associated with the greatest neonatal benefit remains unknown. This study aimed to evaluate whether the time interval from administration of late preterm antenatal corticosteroids to delivery is associated with a change in the likelihood of transient tachypnea of the newborn, respiratory distress syndrome, and hypoglycemia. This was a retrospective cohort study of all singleton neonates who were exposed to 1 or 2 doses of antenatal corticosteroids in the late preterm period (34+0 to 36+6 weeks' gestation) within a large healthcare system between November 2017 and March 2020. Neonates exposed to antenatal corticosteroids before 34 weeks' gestation and those with major fetal structural malformations and chromosomal disorders were excluded. Cases were stratified into the following groups based on the time interval from the first dose of antenatal corticosteroid administration to delivery: <2 days, 2 to 7 days, and >7 days. The primary outcome of transient tachypnea of the newborn was compared among the 3 groups. Secondary outcomes included respiratory distress syndrome and hypoglycemia. A multivariable logistic regression was performed to evaluate the association between the time interval and neonatal outcomes while adjusting for potential confounders. For each outcome, delivery within 2 to 7 days from the first dose of betamethasone administration was defined as the reference group. Data were presented as adjusted odds ratios with 95% confidence intervals, and statistical significance was defined as P < .05. The study cohort comprised 1248 neonates. Of those, 649 (52%) were exposed to 1 dose of antenatal corticosteroids. There were statistically significant differences in the maternal characteristics such as nulliparity, pregnancies complicated by hypertensive disorders and fetal growth restriction, gestational age at antenatal corticosteroid administration, gestational age at delivery, and mode of delivery among the 3 groups. There was a significantly increased risk for transient tachypnea of the newborn (adjusted odds ratio, 4.81; 95% confidence interval, 1.72-12.92) and respiratory distress syndrome (adjusted odds ratio, 9.86; 95% confidence interval, 1.15-84.24) associated with delivery <2 days of antenatal corticosteroid administration. The risk for hypoglycemia was highest in the delivery <2 days group (adjusted odds ratio, 3.44; 95% confidence interval, 2.10-5.63) and decreased as the time interval from antenatal corticosteroid administration to delivery increased (adjusted odds ratio, 0.32; 95% confidence interval, 0.20-0.51 for delivery >7 days). Adverse neonatal outcomes such as transient tachypnea of the newborn, respiratory distress syndrome, and hypoglycemia are more common when late preterm birth occurs <2 days after antenatal corticosteroid administration when compared with birth 2 to 7 days after administration. In addition, delivery >7 days after antenatal corticosteroid administration is associated with a decreased risk for hypoglycemia. Understanding the impact of antenatal corticosteroid timing on neonatal outcomes is essential in caring for patients at risk for late preterm birth.