657 - Risk of Epilepsy in Infants with Retinopathy of Prematurity: A Real-World Dataset Analysis

Publication Number: 2640.657

Huzefa Y. Saria, University of New Mexico School of Medicine, Albuquerque, NM, United States; Jessie Maxwell, University of New Mexico School of Medicine, Albuquerque, NM, United States

Background: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disorder affecting premature infants and is frequently associated with systemic comorbidities. Emerging evidence suggests potential long-term neurologic sequelae in this population; however, the relationship between ROP and subsequent epilepsy development remains underexplored.

Objective: To compare the incidence of epilepsy (ICD-10: G40) among infants diagnosed with ROP versus matched controls without ROP using a large, multicenter electronic health record database.

Design/Methods: A retrospective cohort study was conducted using the TriNetX Research Network, comprised of de-identified patient data from 111 healthcare organizations. Infants were identified at birth using the ICD-10 code Z05, and two cohorts were defined based on the presence or absence of ROP. Propensity score matching was performed using demographics and key neonatal covariates including gestational age, birthweight, and major comorbid conditions (i.e intracranial hemorrhage, cerebral palsy, sepsis, hypoxic-ischemic encephalopathy, and neonatal cerebral leukomalacia). The primary outcome was the incidence of epilepsy (G40) after the neonatal period. A sub analysis stratified the ROP cohort by disease severity: mild (stages 0-2) versus severe (stages 3-5).

Results: A total of 32,147 infants were identified between 2014-2025 and were stratified into a ROP cohort (n=4,706) and Non-ROP cohort (n=27,441). After propensity score matching, 3,314 infants remained in each cohort with balanced demographics and clinical characteristics in ROP versus Non-ROP (mean current age 4.4±2.7 years versus 4.5±2.9 years; 46.6% vs 45.8% female; SMD < 0.05 for all covariates). Infants with ROP displayed a higher risk of developing epilepsy compared to matched controls (3.2% vs. 1.7%; risk ratio=1.84 [95%CI 1.34-2.53], p< 0.001). The ROP sub analysis propensity matched mild (n=598) and severe (n=599) groups showed no significant difference in epilepsy risk (6.4% vs. 6.3%, risk ratio=1.00 [95%CI 0.65-1.55], p=0.99), suggesting epilepsy development is not influenced by ROP severity.

Conclusion(s): In this large, multicenter analysis, infants with a history of ROP, independent of prematurity and other neonatal risk factors, demonstrated nearly a twofold higher risk of developing epilepsy compared to matched controls without ROP. However, epilepsy risk did not vary by ROP severity. These findings highlight the need for possible neurologic surveillance and long-term follow-up in infants with a history of diagnosed ROP regardless of severity.