Prognostic Factors and Sex-Specific Differences in Neonatal Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia.

BACKGROUND

To identify prognostic determinants of short-term outcomes after neonatal hypoxic-ischemic encephalopathy treated with therapeutic hypothermia, with particular focus on sex-specific differences and the role of perinatal sentinel events.

METHODS

Retrospective cohort study of newborns with hypoxic-ischemic injury treated with therapeutic hypothermia at a tertiary center. Clinical, perinatal, and electrophysiological variables were analyzed. Outcomes were in-hospital death and poor composite early clinical severity outcome, defined as an unfavorable course with ≥3 complications, including death. Unadjusted and adjusted prevalence ratios were estimated using Poisson regression with robust variance. Model discrimination was assessed using receiver operating characteristic curves.

RESULTS

Among 393 newborns, 48 (12.2%) died during hospitalization. No overall sex differences were observed in mortality or complication burden. Higher Sarnat stage, severely abnormal electroencephalography background, seizures, and delayed initiation of hypothermia were independently associated with adverse outcomes. The mortality prediction model showed high discrimination (area under the curve 0.861), and the model for poor composite early clinical severity outcome showed moderate discrimination (area under the curve 0.753). Although females more frequently experienced sentinel obstetric events, sex-stratified analyses demonstrated a lower risk of poor composite early clinical severity outcome among exposed females (adjusted prevalence ratio 0.51; 95% confidence interval 0.29-0.89).

CONCLUSIONS

Neurological severity and electroencephalography abnormalities are major predictors of adverse outcomes after hypoxic-ischemic encephalopathy treated with hypothermia. While outcomes were not globally sex-dependent, the interaction between sex and sentinel events suggests sex-specific modulation of vulnerability to intrapartum hypoxia, supporting sex-aware prognostic modeling. However, due to the smaller number of female newborns, the interaction between sex and sentinel events should be interpreted with caution.