Resident Childrens Hospital of Philadelphia Philadelphia, Pennsylvania, United States
Background: Hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment (NDI), though therapeutic hypothermia (TH) improves outcomes for some infants. Characterization of infants who benefit from TH could impact neuroprotective strategies. Animal models for HIE suggest sex-specific differences, but reanalysis of clinical trial data has been limited to 18-22 month outcomes. Objective: To identify possible sex-specific differences in mortality and NDI at 48 months for infants treated with TH for HIE. Design/Methods: This is a retrospective, single-center cohort study of all infants admitted to our hospital’s Level 3 or 4 NICU for HIE and treated with TH from 2013-2019. We included 222 infants: 131 males and 91 females. Clinicians determined TH eligibility as follows: 1)pH < 7.0 or base deficit >16 on cord or first infant blood gas; or pH 7.01-7.16/base deficit 10-15 with acute perinatal event and assisted ventilation or Apgar < 5 at 10 minutes. 2) Encephalopathy on exam. We excluded infants with gestational age < 35 weeks or birthweight < 1800g. Primary outcomes are death or moderate/severe NDI at 48 months, defined as Bayley Scales of Infant Development, 3rd ed composite score < 70, Weschler Intelligence Scale for Children IV composite IQ score < 70, hearing impairment requiring amplification, blindness, or cerebral palsy with Gross Motor Function Classification score 3-5. Secondary outcomes are anti-seizure medicine or vasopressor use during admission, duration of admission, and discharge feeding method.
Data will be aggregated from existing clinical databases with investigators blinded to patient identity. At this time, in-hospital data is awaiting aggregation with follow-up data. We will use summary statistics for demographic elements and calculate relative risks using female infants as the reference group for unadjusted analyses. Outcomes by sex will be compared using chi-squared test with adjustment for gestational age, inborn status, and maternal comorbidity. The CHOP Institutional Review Board determined exemption from review.
