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Early-Onset Neonatal Infection and Epilepsy in Children
Mads Andersen1,2, Niels Bjerregård Matthiesen2,3, May Murra4
1Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Insights
Early-onset neonatal sepsis doubles the risk of childhood epilepsy. Early-onset meningitis significantly increases epilepsy risk, with culture-verified meningitis showing the highest association.
Area of Science:
- Neurology
- Pediatrics
- Infectious Diseases
Background:
- Epilepsy is a prevalent neurological disorder in childhood.
- The link between early-onset neonatal infections and the development of childhood epilepsy is not well understood.
Purpose of the Study:
- To investigate the association between early-onset neonatal infections, specifically sepsis and meningitis, and the subsequent risk of developing childhood epilepsy.
Main Methods:
- A nationwide, population-based cohort study included Danish live-born singletons (gestational age ≥35 weeks) from 1997-2013.
- Early-onset infection was defined as invasive bacterial infection within the first week of life (diagnosed sepsis/meningitis or culture-positive).
- Epilepsy diagnosis was based on hospital records or antiepileptic drug prescriptions, analyzed using Cox regression and incidence rate ratios.
Main Results:
- The study analyzed 981,869 children, with 8,154 diagnosed with sepsis and 152 with meningitis.
- Children with diagnosed sepsis had a 1.85-fold increased risk of epilepsy (HR, 1.85; 95% CI, 1.60-2.13).
- Early-onset meningitis showed a substantially higher risk, with diagnosed and culture-positive cases associated with approximately 10-fold and 16-fold increased epilepsy risks, respectively.
Conclusions:
- Early-onset neonatal sepsis is linked to a significantly increased risk of childhood epilepsy.
- Early-onset meningitis presents a considerably higher risk for epilepsy development compared to sepsis.
- These findings highlight the importance of preventing and managing neonatal infections to mitigate long-term neurological sequelae like epilepsy.
Importance:
Epilepsy is a common neurological disorder in childhood. It remains unclear whether early-onset sepsis is associated with epilepsy and to what extent early-onset meningitis may contribute to its development.
Objective:
To study the association between early-onset neonatal infection and childhood epilepsy.
Design, Setting, And Participants:
Nationwide, population-based, register-based cohort study of all Danish live-born singletons with at least 35 completed gestational weeks at birth without major congenital anomalies in Denmark between 1997 and 2013 with follow-up until 2021 or age 18 years, whichever came first. Data were analyzed from February 2024 to January 2025.
Exposures:
Early-onset infection was defined as an invasive bacterial infection during the first week of life. Diagnosed infection was defined by diagnostic codes of sepsis or meningitis, while culture-positive infection only included those with bacterial pathogens cultured from blood or cerebrospinal fluid.
Main Outcomes And Measures:
Epilepsy was defined as a hospital diagnosis or at least 2 redeemed prescriptions of antiepileptic medication. The association between diagnosed sepsis and epilepsy was investigated with multivariable Cox regression to estimate adjusted hazard ratios (HR) with 95% CIs. Associations for the remaining definitions of infection were investigated using person-time incidence rate ratios (IRR).
Results:
Among 981 869 children, the median (IQR) gestational age was 40 (39-41) weeks, 501 615 (51%) were male, 8154 (0.8%) were diagnosed with sepsis, and 152 (<0.1%) were diagnosed with meningitis. Of these, 257 children had culture-positive sepsis and 32 had culture-positive meningitis. The incidence rate of epilepsy was 1.6 per 1000 person-years for children with diagnosed sepsis compared with 0.9 per 1000 person-years for children without an infection, resulting in an adjusted HR of 1.85 (95% CI, 1.60-2.13). Culture-positive sepsis was also associated with an increased risk of epilepsy (IRR, 2.70; 95% CI, 1.08-5.56), while the highest risks were observed in children with meningitis both diagnosed (IRR, 9.85; 95% CI, 5.52-16.27) and verified by culture (IRR, 16.04; 95% CI, 5.21-37.46).
Conclusions And Relevance:
In this nationwide cohort study, early-onset neonatal sepsis was associated with an approximately 2-fold increased risk of childhood epilepsy. As expected, early-onset meningitis was associated with an even higher risk of epilepsy with an approximately 10-fold increase.
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