Simple congenital heart diseases (CHD) are associated with various central nervous system diseases, including epilepsy. This study aimed to compare the risk of epilepsy in patients with different types of simple CHD. In this prospective cohort study, from January 2008 to June 2022, patients with atrial septal defect (ASD), patent foramen ovale (PFO), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) were recruited at the Registration Center of CHD in West China Hospital. Follow-up was conducted yearly until the diagnosis of epilepsy, loss to follow-up, or end of study. The outcomes included a comparison of epilepsy incidence according to different simple CHD types and a risk assessment of developing epilepsy. Multivariable Poisson regression was performed to adjusted factors of demographics and disease history. Of 10,914 patients who met the inclusion criteria, 108 were diagnosed with epilepsy at an average follow-up of 2.19 years. Epilepsy incidence in patients with PFO, VSD, PDA, and ASD was 8.58/1000, 4.85/1000, 3.98/1000, and 2.63/1000 person-years, respectively. Compared with ASD patients (reference group), the risk ratios (95% confidence intervals) in patients with PFO, VSD, and PDA were 3.28 (2.00-5.43), 1.47 (0.79-2.68), and 1.46 (0.70-2.82), respectively. Subgroup analyses determined that patients with simple CHD who underwent CHD surgery demonstrated a lower risk of epilepsy than those who did not. Among the major types of simple CHD, PFO was associated with a significantly higher risk of epilepsy, while the risk was reduced in those who underwent PFO closure procedures.
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