Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

Abstract

Objective: Progesterone administration has been associated with improved neurologic outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of intraventricular hemorrhage in infants born before 32 weeks’ gestation. Study Design: This is a retrospective study of liveborn singleton deliveries between 20-32 weeks’ gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC) in the antepartum period and diagnosis of IVH (Grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association of 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (OR) and 95% confidence intervals (CI) are presented. Results: Among 749 neonates born between 20-32 weeks’ gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC, and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (aOR 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born < 28 weeks’ gestation or those with very low birthweight (<1500g) were at increased risk of intraventricular hemorrhage (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). Conclusion: Antenatal maternal 17-OHPC administration was not associated with risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impacts rates of neonatal IVH.