Neonatal Bacterial Infections Linked to Increased Risk for Epilepsy

Children who experience bacterial infections in the first week of life may face a significantly increased risk of developing epilepsy during childhood, according to results published in JAMA Network Open.

Researchers examined long-term risk for epilepsy following early-onset neonatal infections among live-born singleton infants between 1997 and 2013. Children were followed until they turned age 18 or until June 2021. A total of 981,869 near- and full-term children were included in the analysis. Median gestational age was 40 (IQR, 39-41) weeks, and 51% were boys.

Of the participants, 8154 (0.8%) were diagnosed with sepsis, and 152 (<0.1%) were diagnosed with meningitis during the first week of life. Culture-positive infections were confirmed in 257 children with sepsis and 32 with meningitis. The most common pathogens were group B Streptococcus, Staphylococcus aureus, and Escherichia coli.

During the study period, 12,228 (1.2%) children developed epilepsy. Epilepsy onset occurred earlier in children with early infections, at a median age of 6 (IQR, 2-10) years, compared with 7 (IQR, 3-12) years in those without neonatal infection. Incidence of epilepsy was 1.6 per 1000 person-years (PYs) in children with neonatal sepsis, compared with 0.9 per 1000 PYs in those without infection (adjusted hazard ratio [aHR], 1.85; 95% CI, 1.60-2.13).

Stratified analyses revealed a stronger association with focal epilepsy (HR, 2.94; 95% CI, 2.30-3.75) than with generalized epilepsy (HR, 1.46; 95% CI, 1.05-2.05). Culture-positive sepsis was also linked to increased epilepsy risk (incidence rate ratio [IRR], 2.70; 95% CI, 1.08-5.56).

Meningitis carried an even greater risk. Children with diagnosed meningitis had an epilepsy IRR of 8.6 per 1000 PYs (IRR, 9.85; 95% CI, 5.52-16.27), while those with culture-confirmed meningitis had a rate of 13.5 per 1000 PYs (IRR, 16.04; 95% CI, 5.21-37.46).

Study limitations include potential diagnostic misclassification, inability to assess pathogen-specific risk, and possible survivor bias underestimating risk.

“This nationwide cohort study of near-term and full-term children found an association between early-onset neonatal infection, defined by both diagnoses and bacterial cultures, and childhood epilepsy,” the study authors concluded.

Disclosures: This research was supported by the Graduate School of Health at Aarhus University, Elsass Foundation, Helsefonden, and Beckett Foundation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.