Abstract
IMPORTANCE: The risk of epilepsy after neonatal invasive Group B Streptococcus (iGBS) disease, particularly iGBS sepsis, is poorly understood. OBJECTIVE: To examine the association between neonatal iGBS (sepsis or meningitis) and long-term risk of epilepsy, stratified by sex, prematurity, and maternal socioeconomic position (SEP). DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted in Denmark with an inclusion period from 1997 through 2017 and follow-up until the end of 2018. A general population comparison cohort was randomly sampled and matched up to 10:1 to the exposed cohort. Linkage between Danish national registers were applied for data collection. Participants were infants aged 0 to 89 days. The general population comparison cohort was matched by sex, the child's year and month of birth, and gestational age. SEP was defined by maternal income and education. EXPOSURE: Hospital-diagnosed iGBS (sepsis or meningitis) during the first 89 days after birth. OUTCOMES AND MEASURES: Epilepsy was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and/or prescription codes for antiepileptic drugs using Danish medical registry data. Cumulative risk (CR) of epilepsy was calculated by treating death as a competing event. Cox proportional hazards regression was used to estimate hazard ratios with 95% CIs. Effect modification by sex, prematurity, and maternal SEP was assessed on an additive scale. RESULTS: A total of 1432 children (792 [55.3%] boys; 1126 [78.6%] with gestational age ≥37 weeks) were identified with iGBS disease: 1264 with sepsis and 168 with meningitis. In the comparison cohort, there were 14 211 children (7869 [55.4%] boys; 11 260 [79.2%] with gestational age ≥37 weeks). The overall (0 to 22 years) CR of epilepsy was 3.6% (95% CI, 2.6%-5.0%) in children with iGBS disease and 2.3% (95% CI, 1.9%-2.7%) in the comparison cohort. The overall CR of epilepsy for iGBS meningitis was 15.1% (95% CI, 8.9%-22.8%) and 2.2% (95% CI, 1.4%-3.4%) for iGBS sepsis. The adjusted hazard ratio for epilepsy in children with iGBS disease was 2.04 (95% CI, 1.46-2.85). Being a boy, born premature, or born to a mother belonging to a low SEP group was associated with an increased risk of epilepsy in later childhood. CONCLUSION: In this population-based cohort study of 1432 neonates, iGBS disease was associated with a higher incidence of epilepsy in later childhood, notably after meningitis. Premature birth, sex, and low maternal SEP modified the association.