Epilepsy in early childhood was significantly elevated among those infected in early infancy with invasive Group B Streptococcus (iGBS) meningitis, but not in those with iGBS sepsis, according to a matched cohort study out of Denmark.

Cumulative risk for epilepsy through 22 years was 3.6% for people who contracted iGBS meningitis or sepsis in the first 3 months of life, as compared with 2.3% in a control group without an iGBS diagnosis (adjusted hazard ratio [aHR] 2.04, 95% CI 1.46-2.85), reported researchers led by Malene Risager Lykke, MD, of Aarhus University Hospital in Denmark.

As detailed in JAMA Network Open, the bulk if not all of the increased risk was in the first 5 years of life (3.18, 95% CI 2.10-4.83), with no significant risk seen thereafter.

The population-wide study, which included more than 1,400 neonates with iGBS meningitis or sepsis matched to controls, showed that the increased cumulative risk for epilepsy was driven entirely by meningitis.

Epilepsy occurred in 15.1% of the infants with iGBS meningitis over the 22-year study period versus 1.4% of controls (aHR 15.68, 95% CI 8.07-30.49), but in just 2.2% of iGBS sepsis cases versus 2.4% of controls (aHR 1.06, 95% CI 0.67-1.67).

“These findings suggest that epilepsy should be added to the list of neurological outcomes following iGBS disease in early infancy, especially meningitis,” the study authors wrote.

Lykke’s group noted that prior studies looking at iGBS and epilepsy were typically small, and focused primarily on meningitis, while the current research “addresses an important epidemiological question, particularly for iGBS sepsis.”

A leading cause of neonatal mortality worldwide, iGBS disease has also been associated with maternal death, stillbirth, and neurodevelopmental impairment in survivors, “including neonatal stroke, encephalopathy, cerebral palsy, intellectual and/or motor, vision, or hearing impairment,” the group explained.

In 2020, there were an estimated 20 million pregnant women with Group B Streptococcus rectovaginal colonization worldwide, with an estimated 500,000 cases of iGBS disease that occurred in neonates within 3 months of birth.

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

While most subgroups with iGBS had an elevated risk for epilepsy in later childhood, the association was higher among boys, preterm infants, and babies born to lower-income mothers.

Using multiple national registries, Lykke’s group identified 1,432 children diagnosed with iGBS disease through 89 days of birth (88.3% with sepsis, 11.7% with meningitis) from the general population of nearly 1.3 million liveborn Danish children from 1997 to 2017. Case patients were matched 1:10 to a comparison group of 14,211 children who had no history of iGBS (by sex, year/month of birth, and gestational age).

Median follow-up for the iGBS group was 12.6 years and 13.3 years for the control group. In each, just over half (55%) were male, and 79% were born at a gestational age of 37 weeks. Over 90% were singleton births, and the maternal age was 30 years or older in a majority.

In the first 5 years life, the incidence rates (IRs) for epilepsy — defined by ICD-10 codes and/or prescription codes for antiepileptic drugs — were 4.5 versus 1.4 per 1,000 person-years for the iGBS and non-iGBS groups, respectively. Beyond this period, IRs were 1.1 and 1.0 per 1,000 person-years.

Noted limitations included that some iGBS cases may have been missed; and that childhood accidents including head trauma, drug use, or infectious diseases were not accounted for following the index date (hospital admission for iGBS).