Early-life Meningitis Associated with Risk of Developing Epilepsy in Later Childhood

Infants exposed to invasive Group B Streptococcus (iGBS) meningitis during their first 3 months of life could have a greater risk of developing epilepsy in later childhood compared to infants who were not exposed, according to a 20-year study conducted from Denmark that was recently published in JAMA Network Open.

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iGBS is a leading cause of neonatal/young infant mortality. It is also associated with maternal death, stillbirth, and neurodevelopmental impairment (NDI) in the surviving neonates. NDIs include stroke, encephalopathy, cerebral palsy, intellectual and/or motor, vision, hearing impairment, sepsis, and meningitis. Among the limited and small studies that analyze NDI outcomes, most focus on meningitis.

Meningitis may cause epilepsy following neonatal iGBS disease. However, more research is needed to understand iGBS disease on the risk of long-term epilepsy, and the risk among patients with neonatal iGBS sepsis. Investigators evaluated the cumulative risk (CR) of an infant diagnosed with iGBS sepsis or meningitis during the first 3 months of age developing epilepsy. The team accounted for sex, prematurity, and maternal socioeconomic position (SEP) as effect modification factors.

From 1997 to 2017, investigators calculated cases of hospital-diagnosed iGBS during the first 89 days after birth in a cohort of 1432 children with iGBS disease (1264 with sepsis and 168 with meningitis). They compared these infants with a cohort of 14,211 liveborn children free of iGBS disease (gestational age of 37 weeks or more).

The overall CR of developing epilepsy into later childhood was 3.6% among children with iGBS disease, wheras the CR of later-adulthood epilepsy was 2.3% in the control group. In addition, the CR of developing epilepsy among infants with iGBS meningitis was 15.1%, whereas the CR was more than 7-times lower (2.2%) in infants with iGBS sepsis.

Among children with iGBS meningitis, the overall incidence rate (IR) of epilepsy was 13.6 per 1000 person-years (PY); iGBS sepsis had an IR of 1.3 per 1000 PY. However, IR in patients with iGBS disease versus the control was 2.4 and 1.2 per 1000 PY, respectively.

Sex, premature birth, and low maternal SEP were risk factors. Being male, being born premature, or having a mother of low SEP, defined by maternal income and education, were associated with an increased CR risk of later-childhood epilepsy.

Among study limitations were the inclusion of children with undiagnosed iGBS disease or those who were misclassified. Investigators also did not account for childhood accidents, infectious disease, or head trauma that can lead to disease. Further, they did not identify all possible subgroups, SEPs, or unmeasured confounding factors.

“Our findings have implications for estimating the global burden of iGBS and should be considered in relation to the cost-effectiveness of interventions, such as intrapartum antibiotic prophylaxis and maternal vaccination,” the study authors wrote. “These data also have implications for affected individuals and underline the need for better long-term follow-up and care.”

Reference

Lykke M, Sørensen H, Lawn J, et al. Long-term Risk of Epilepsy Following Invasive Group B Streptococcus Disease in Neonates in Denmark. JAMA Netw Open. 2023; doi:10.1001/jamanetworkopen.2023.9507