Epilepsy and Neurodevelopment Outcomes 24 Months after Neonatal Hypoxic–Ischemic Encephalopathy and Predictive Factors of Post-neonatal Epilepsy

This retrospective, dual-center Italian study assessed the incidence, electroclinical characteristics, and risk factors for post-neonatal epilepsy among neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). The study aims to better define the long-term risk factors for developing epilepsy or neurodevelopmental issues.We included neonates with HIE who underwent TH. Neurological examination and general movements were assessed before and after TH. Amplified-integrated EEGs (aEEG) or polygraphic EEGs (pEEG) were performed within 6 hours of life; a pEEG was performed after TH (72 hours to 10 days) and at 3, 9 to 12, and 24 months, and then yearly. Brain MRI was conducted within 30 days. The 24-month developmental outcome was evaluated using Griffiths Mental Development Scales. The median follow-up duration was 48 months. Epilepsy was classified according to ILAE criteria.We enrolled 159 patients: 15 (9.4%) developed epilepsy. Nine (5.6%) had onset before 24 months; three of them developed infantile epileptic spasm syndrome (IESS). Seizure onset was after 24 months in 6/159 individuals (3.8%). At the last follow-up, all 15 patients had focal epilepsy. Global development was pathological in 11/15 (10/15 <2SD; 1/15 <1SD). Risk factors for post-neonatal epilepsy included: MRI lesions involving the basal ganglia and thalamus (<i>p</i> < 0.0001), severe HIE (<i>p</i> = 0.0008), and severe anomalies on the pEEG recorded pre-TH (<i>p</i> = 0.0032) and post-TH (<i>p</i> = 0.0071).Our study confirms that post-neonatal epilepsy is rare and generally well-controlled. MRI, HIE-3, and early pEEGs are key predictors. High-risk patients should be screened for IESS in the early months, and patients with electroclinical and neuroradiological risk factors should continue long-term neurological follow-up beyond 24 months.