# Long-Term Neurodevelopmental Outcomes and Prognostic Factors in Neonates with Hypoxic–Ischemic Encephalopathy

## TL;DR

This study examines long-term brain development outcomes in babies with hypoxic-ischemic encephalopathy and identifies early factors that predict poor outcomes.

## Contribution

The study identifies new independent prognostic factors, including lactate levels, Apgar score, and renal dysfunction, in neonates with HIE.

## Key findings

- 18.2% of neonates with HIE experienced severe neurodevelopmental impairment or death.
- Higher lactate levels and lower 5-minute Apgar scores were independently linked to poor outcomes.
- Renal dysfunction and multiorgan failure were strongly associated with adverse neurodevelopmental outcomes.

## Abstract

Background: Hypoxic–ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and long-term neurodevelopmental impairment despite advances in perinatal care and the widespread use of therapeutic hypothermia. Reliable early prognostic markers are essential for risk stratification and long-term follow-up planning. This study aimed to evaluate long-term neurodevelopmental outcomes and associated prognostic factors in neonates with HIE treated in the era of therapeutic hypothermia. Methods: This retrospective cohort study was conducted in a tertiary neonatal intensive care unit between January 2020 and June 2024. Neonates with gestational age ≥ 35 weeks diagnosed with HIE were included. Clinical characteristics, laboratory parameters, neurophysiological findings, neuroimaging results, and indicators of multiorgan dysfunction were recorded. Long-term neurodevelopmental outcomes were assessed at 18 to 24 months of age. The primary outcome was death or severe neurodevelopmental impairment. Multivariable logistic regression analysis was performed to identify independent predictors of adverse outcomes. Results: A total of 99 neonates were included. Therapeutic hypothermia was administered to 86 (86.9%) infants. Severe neurodevelopmental impairment or death occurred in 18 (18.2%) patients. Cerebral palsy was diagnosed in 19 (20.9%) survivors, developmental delay in 12 (13.2%), epilepsy in 16 (17.6%), and feeding difficulties in 9 (9.9%). In multivariable analysis, higher lactate levels (adjusted OR = 1.239, 95% CI = 1.052–1.458), lower Apgar score at 5 min (adjusted OR = 0.570, 95% CI = 0.344–0.944), and renal dysfunction (adjusted OR = 7.947, 95% CI = 2.027–31.164) were independently associated with severe neurodevelopmental impairment or death. Multiorgan dysfunction and abnormal neurophysiological and neuroimaging findings were significantly associated with adverse outcomes. Conclusions: Early biochemical markers, neurological assessments, neurophysiological recordings, neuroimaging patterns, and systemic organ dysfunction are closely associated with long-term neurodevelopmental outcomes in neonates with HIE. A multidimensional approach to early prognostic evaluation may improve risk stratification and guide targeted follow-up and intervention strategies.