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Neonatal encephalopathy and 3 year outcomes: a French population-based cohort

Pediatr Res. 2026 Apr 30. doi: 10.1038/s41390-026-05022-3. Online ahead of print.

ABSTRACT

BACKGROUND: To assess rates and factors for disability at 3 following hypoxic-ischemic encephalopathy (HIE).

METHODS: Newborns more than 34 weeks with HIE Sarnat grades I to III, mostly treated by hypothermia were included in the population-based cohort LyTONEPAL and followed at 3. Mild, moderate, or severe neurodevelopment was defined on motor, sensorial impairment, epilepsy and neurodevelopmental delay. Main measurement was relative risk ratio (aRRR) and 95% CI of disability, adjusted for birth circumstances and neonatal complications, estimated on complete and imputed cases.

RESULTS: 647 out of 794 newborns survived, and 463 were assessed. Severe, moderate or mild neurodevelopmental impairment was observed in 10.5% (95% CI 7.6-14.1), 11.8% (95% CI 8.7-15.6) and 22.0% (95% CI 17.9-26.6), respectively. Moderate to severe outcome was increased with an abnormal examination at discharge (aRRR=4.22, 95% CI 1.74-10.25) and hypoglycemia (aRR=8.54, 95%CI 1.88-38.73.05) while hypothermia decreased it (aRRR=0.36 95% CI 0.13-0.99). Mild outcome was associated with neonatal infection (aRRR 3.73, 95% CI 1.55-8.98-8.36), while higher gestational age seemed protective (aRRR 0.83, 95% CI 0.69-1.00).

CONCLUSION: Four in 10 HIE had neurodevelopmental sequelae, half of which were mild. A more immature brain or exposure to neonatal infection seemed to worsen prognosis, irrespective of disease severity.

TRIAL REGISTRATION: Clinical trials registry, NCT02676063, ClinicalTrials.gov.

IMPACT: Follow-up at 3 in a 647 children with HIE Sarnat grades I to III, mostly treated by hypothermia showed impairment of motor, sensorial and learning skills in 44.4%, of which 10.5% and 11.8% were moderate and severe respectively. 45.7% of children have at least one rehabilitation treatment, including 26% of children with favorable outcome. Neonatal infection increased the risk of unfavorable evolution, while more advanced gestational age and hypothermia were protective. In addition to clinical or MRI severity, our data suggest to integrate gestational age and neonatal infection into early prognostic assessment, and extending HIE follow-up to school age.

PMID:42062519 | DOI:10.1038/s41390-026-05022-3

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