Early-Infancy Meningitis Infection Linked With Increased Risk of Epilepsy

Epilepsy should be added to the list of neurological outcomes following an infection of invasive Group B Streptococcus (iGBS)—particularly meningitis—in early infancy, new study results suggest.

Findings from a population-based cohort study, published in JAMA Network Open, revealed iGBS disease was linked with a higher incidence of epilepsy in later childhood, notably after meningitis. The risk of epilepsy in later childhood was higher among those born prematurely, males, or those born to a mother belonging to a low socioeconomic position (SEP).

iGBS disease is a leading cause of neonatal and young infant mortality around the world. In 2020, it was estimated that 500,000 cases of iGBS disease occurred within the first 3 months after birth, the authors wrote.

Although epilepsy has been reported as an outcome following iGBS disease, particularly meningitis, the risk of the condition after neonatal iGBS disease has yet to be investigated further, the researchers said. To address this knowledge gap, they studied children with iGBS born in Denmark between 1997 and 2017. Follow-up continued until the end of 2018.

A total of 1432 children with iGBS disease (sepsis, n = 1264; meningitis, n = 168) were included in the study and compared with 14,211 unaffected children. All participants were aged between 0 and 89 days, 55.3% were male, and nearly 79% had a gestational age of at least 37 weeks. The mother’s SEP was determined via income and education level.

Analyses revealed:

• The overall cumulative risk 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 cumulative risk of epilepsy for iGBS meningitis was 15.1% (95% CI, 8.9%-22.8%) and for iGBS sepsis, 2.2% (95% CI, 1.4%-3.4%)
• The adjusted HR 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

Overall, “we found a significantly higher risk of epilepsy in children with iGBS meningitis in later childhood compared with children not exposed to iGBS,” the authors wrote. “The risk of epilepsy for iGBS sepsis was not significant.”

Compared with those without iGBS, the cumulative incidence of epilepsy was higher within the first 5 years after diagnosis of iGBS.

To the authors’ knowledge, the study is the first to examine the long-term risk of epilepsy as an individual outcome after iGBS sepsis or meningitis.

The large cohort of children with iGBS disease and comparison group, in addition to long-term follow-up until adolescence, mark strengths of the current investigation. Researchers were also able to match groups on all matching variables with small differences between cohorts, helping to reduce residual confounding.

However, data for iGBS onset were defined based on admission date, meaning the study may have excluded iGBS infections from the day of birth. Results should also be interpreted with caution, due to the small size of the iGBS meningitis cohort, the authors noted. Data also did not account for childhood accidents, infectious diseases, or head trauma that took place after the index date.

“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 authors concluded. “Importantly, these data also have implications for affected individuals and underline the need for better long-term follow-up and care.”

Reference

Lykke MR, Sørensen HT, Lawn JE, Horváth-Puhó E. Long-term risk of epilepsy following invasive group B Streptococcus disease in neonates in Denmark. JAMA Netw Open. Published online April 21, 2023. doi:10.1001/jamanetworkopen.2023.9507