Do Premature Infants Have a Greater Risk of Developing Adult-Onset Epilepsy?
Yes, premature infants have a significantly increased risk of developing epilepsy that persists from childhood into adulthood, with the risk inversely proportional to gestational age—the earlier the birth, the higher the epilepsy risk throughout life. 1
Magnitude of Risk
The risk of epilepsy in premature infants is substantially elevated compared to term-born children:
- Preterm infants (<37 weeks) have 2.16 times higher odds of developing epilepsy compared to full-term infants, and this association persists throughout childhood into adulthood 1
- Extremely premature infants (<32 weeks) face even greater risk, with 2.73 times higher odds of epilepsy compared to moderate preterm infants (32-36 weeks) 1
- Among very preterm infants (<32 weeks, <1500g birth weight) followed to age 5 years, the overall incidence of epilepsy is 2.8%, which is substantially higher than the general population risk of approximately 1% 2
Critical Risk Stratification by Neonatal Complications
The epilepsy risk in premature infants is dramatically amplified by specific neonatal morbidities 2:
- Neonatal seizures: 33% develop epilepsy 2
- Cystic periventricular leukomalacia (cPVL): 27% develop epilepsy 2
- High-grade intraventricular hemorrhage (IVH): 21% develop epilepsy 2
- Necrotizing enterocolitis (NEC) stage III: 20% develop epilepsy 2
- Significant neonatal brain injury (high-grade IVH or cPVL): 21.6% develop epilepsy, compared to only 1% in preterm infants without such injury 2
Timing and Pattern of Epilepsy Development
The onset of epilepsy following neonatal complications shows distinct temporal patterns 3:
- Cumulative incidence through early childhood reaches 21.6% among neonates with acute provoked seizures 3
- Earlier epilepsy onset is predicted by: ≥3 days of neonatal seizures (HR=2.8), abnormal discharge neurological exam (HR=2.4), and deep gray/brainstem injury (HR=2.4) 3
- Paradoxically, prematurity (<37 weeks) is associated with later epilepsy onset (HR=3.7), meaning preterm infants may develop epilepsy later in childhood rather than in infancy 3
- The prevalence of epilepsy declines by 9.2% per week of gestation toward term birth, demonstrating a clear dose-response relationship between degree of prematurity and epilepsy risk 4
Clinical Burden and Severity
Premature infants who develop epilepsy face substantial morbidity 2, 3:
- 42% develop drug-resistant epilepsy, particularly those with neonatal high-grade IVH 2
- 50% develop intractable epilepsy requiring multiple medications 3
- 40% require intensive care unit admission for seizure management 3
- Neurodevelopmental disability is common regardless of whether neonatal brain injury was present 2
Long-Term Neurological Outcomes Beyond Epilepsy
Preterm infants requiring surgical treatment for posthemorrhagic hydrocephalus remain at high risk for multiple neurological sequelae 5:
- Cerebral palsy 5
- Epilepsy 5
- Cognitive and behavioral delays 5
- Attention deficit disorders in adolescence 5
Critical Clinical Pitfall
Do not assume epilepsy risk is limited to early childhood. The association between preterm birth and epilepsy persists throughout childhood into adulthood, requiring long-term surveillance even in premature infants who appear neurologically normal in early life 1. The later onset pattern in preterm infants means that epilepsy may not manifest until school age or beyond 3.
Surveillance Recommendations
For premature infants, particularly those with the high-risk neonatal morbidities identified above, risk factor stratification should guide clinical surveillance decisions and family counseling 3. While specific surveillance protocols are not definitively established, the evidence supports heightened clinical vigilance throughout childhood and into adulthood for this population.