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Long-term Risk of Epilepsy Following Invasive Group B Streptococcus Disease in Neonates in Denmark - PubMed

  • ️Sun Jan 01 2023

Long-term Risk of Epilepsy Following Invasive Group B Streptococcus Disease in Neonates in Denmark

Malene Risager Lykke et al. JAMA Netw Open. 2023.

Erratum in

  • Error in Figure 2.

    [No authors listed] [No authors listed] JAMA Netw Open. 2024 Oct 1;7(10):e2442173. doi: 10.1001/jamanetworkopen.2024.42173. JAMA Netw Open. 2024. PMID: 39365592 Free PMC article. No abstract available.

Abstract

Importance: The risk of epilepsy after neonatal invasive Group B Streptococcus (iGBS) disease, particularly iGBS sepsis, is poorly understood.

Objective: To examine the association between neonatal iGBS (sepsis or meningitis) and long-term risk of epilepsy, stratified by sex, prematurity, and maternal socioeconomic position (SEP).

Design, setting, and participants: This population-based cohort study was conducted in Denmark with an inclusion period from 1997 through 2017 and follow-up until the end of 2018. A general population comparison cohort was randomly sampled and matched up to 10:1 to the exposed cohort. Linkage between Danish national registers were applied for data collection. Participants were infants aged 0 to 89 days. The general population comparison cohort was matched by sex, the child's year and month of birth, and gestational age. SEP was defined by maternal income and education.

Exposure: Hospital-diagnosed iGBS (sepsis or meningitis) during the first 89 days after birth.

Outcomes and measures: Epilepsy was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and/or prescription codes for antiepileptic drugs using Danish medical registry data. Cumulative risk (CR) of epilepsy was calculated by treating death as a competing event. Cox proportional hazards regression was used to estimate hazard ratios with 95% CIs. Effect modification by sex, prematurity, and maternal SEP was assessed on an additive scale.

Results: A total of 1432 children (792 [55.3%] boys; 1126 [78.6%] with gestational age ≥37 weeks) were identified with iGBS disease: 1264 with sepsis and 168 with meningitis. In the comparison cohort, there were 14 211 children (7869 [55.4%] boys; 11 260 [79.2%] with gestational age ≥37 weeks). The overall (0 to 22 years) CR 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 CR of epilepsy for iGBS meningitis was 15.1% (95% CI, 8.9%-22.8%) and 2.2% (95% CI, 1.4%-3.4%) for iGBS sepsis. The adjusted hazard ratio 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.

Conclusion: In this population-based cohort study of 1432 neonates, iGBS disease was associated with a higher incidence of epilepsy in later childhood, notably after meningitis. Premature birth, sex, and low maternal SEP modified the association.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sørensen reported that the Department of Clinical Epidemiology, Aarhus University, receives funding for other studies from the European Medicines Agency and companies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Risk of Epilepsy According to Follow-up Time in Years

Numbers at risk at index date and after 5, 10, and 15 years of follow-up for the exposed (with invasive group B Streptococcus [iGBS]) and comparison cohort (without iGBS).

Figure 2.
Figure 2.. Analyses Stratified by Children’s Characteristics and Maternal Socioeconomic Position

The figure shows cumulative risk (CR) with 95% CIs for the iGBS and comparison (non-iGBS) cohorts and the adjusted HRs with 95% CIs. HR indicates the adjusted hazard ratio, where we have adjusted for sex, prematurity, year of birth, and maternal income with 95% CI; iGBS, invasive group B Streptococcus.

Figure 3.
Figure 3.. Effect Modification Analysis

Proportion of the incidence rate per 1000 person-years attributable to baseline rate, modifying variable alone (sex, prematurity, maternal education), invasive group B Streptococcus (iGBS) disease alone, and the interaction.

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