(38) Sex Differences in Neonatal Hypoxic-ischemic Encephalopathy: Clinical Outcomes and Neurodevelopmental Implications

Background: Hypoxic Ischemic Encephalopathy (HIE) is a major contributor to neonatal morbidity and mortality worldwide. While preclinical studies suggest that male neonates experience worse outcomes than females, there is currently a lack of definitive clinical data to support this observation.

Objectives: Our objective is to investigate sex differences in neurodevelopmental outcomes among neonates diagnosed with HIE.

Design/Methods: This is an IRB approved retrospective analysis of patients admitted to the UW-Madison American Family Children’s Hospital NICU between 2010 and 2024. Using the clinical information on neonates with HIE included in Children's Hospital's Neonatal Consortium Database (CHND), the study team received a data pull from CHND that included demographics, birth, therapeutic hypothermia, EEG, seizures, NICU therapies. Missing data and neurodevelopment outcomes extracted from Health Link, in addition to neuroimaging (MRI) before NICU discharge and injury scored using Weeke Method. All data will be entered the REDCAP data base.

Results: Of the 91 infants included in the study, 58 (63.7 %) were male and 33 (36.3 %) were female. The mean gestational age was 38.37 ± 1.83 weeks, and the mean birth weight was 3221 ± 75 g. Based on clinical exam, 50 infants (55 %) were classified as having moderate, 23 (25 %) severe, and 18 (20 %) mild HIE. Six infants (3 male-3 female) died during the NICU stay-all had severe HIE. Among infants with a history of cardiac arrest, 64 % were male and 36 % were female. Among those who required vasoactive support, 57 % were male and 43 % were female. MRI data was available for 86 neonates. Cerebellar scores were similar across severity groups, while cortical (p=0.0001), subcortical (p=0.0001), and white matter injuries (p=0.0001) were higher in severe HIE. No sex differences were detected in the MRI injury severity (Table 1). Seizures were detected by EEG in 25.8% of male infants and 21% of female infants. Among neonates with abnormal General Movements Assessment (GMA) in the NICU, 64.1 % were male neonates.

Conclusions: No sex differences were detected GMA at NICU discharge. However, males seem to be more susceptible to seizures and had worse GMA in the NICU. EEG analysis are pending. Considering the evolution of the brain injury beyond the NICU discharge, ongoing NICU follow up clinic neurodevelopmental assessments analysis may reveal sex specific susceptibility of neonatal brains to HIE.