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TY - JOUR

T1 - Short-term and long-term risk of mortality and neurodevelopmental impairments after bacterial meningitis during infancy in children in Denmark and the Netherlands

T2 - a nationwide matched cohort study

AU - Snoek, Linde

AU - Gonçalves, Bronner P.

AU - Horváth-Puhó, Erzsébet

AU - van Kassel, Merel N.

AU - Procter, Simon R.

AU - Søgaard, Kirstine K.

AU - Chandna, Jaya

AU - van der Ende, Arie

AU - van de Beek, Diederik

AU - Brouwer, Matthijs C.

AU - Sørensen, Henrik T.

AU - Lawn, Joy E.

AU - Bijlsma, Merijn W.

N1 - Funding Information: We thank PeriNed and Statistics Netherlands for their cooperation and for making their valuable data available for this study. We also thank the NRLBM for the collection of isolates, thereby allowing for the identification of patients with bacterial meningitis. We also thank Statistics Denmark and the teams that manage the Danish Civil Registration System and the Danish National Patient Registry. This work was supported by a grant (OPP1180644) from the Bill & Melinda Gates Foundation to the London School of Hygiene & Tropical Medicine (to JEL) and Aarhus University, the Stichting Remmert Adriaan Laan Fonds (to DvdB), and the Netherlands Organisation for Health Research and Development (Dutch Research Council-Vici grant [number 918.19.627] to DvdB). Funding Information: We thank PeriNed and Statistics Netherlands for their cooperation and for making their valuable data available for this study. We also thank the NRLBM for the collection of isolates, thereby allowing for the identification of patients with bacterial meningitis. We also thank Statistics Denmark and the teams that manage the Danish Civil Registration System and the Danish National Patient Registry. This work was supported by a grant (OPP1180644) from the Bill & Melinda Gates Foundation to the London School of Hygiene & Tropical Medicine (to JEL) and Aarhus University, the Stichting Remmert Adriaan Laan Fonds (to DvdB), and the Netherlands Organisation for Health Research and Development (Dutch Research Council-Vici grant [number 918.19.627] to DvdB). Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PY - 2022/9/1

Y1 - 2022/9/1

N2 - Background: Few studies have reported the long-term consequences of bacterial meningitis during infancy, and studies that have been done usually do not include a comparison cohort. We aimed to assess short-term and long-term risk of mortality, neurodevelopmental impairment (NDI), and health-care use and household income in cohorts of children with and without a history of bacterial meningitis during infancy in Denmark and the Netherlands. Methods: In this nationwide cohort study, infants with a history of bacterial meningitis before age 1 year were identified through the Danish Medical Birth Registry and Danish National Patient Registry using International Classification of Diseases (ICD)-10 codes and through the Netherlands Reference Laboratory for Bacterial Meningitis. Infants were matched (1:10) by sex and birth month and year to a comparison cohort of the general population without a history of bacterial meningitis. We analysed mortality using Cox proportional hazards regression. In Denmark, diagnoses of NDIs were based on ICD-10 codes; in the Netherlands, special educational needs were used as a functional NDI outcome. Risk ratios (RRs) of NDIs were estimated using modified Poisson regression. We also analysed long-term health-care use in Denmark and household income in both countries. All regression analyses were adjusted for sex and year of birth, and stratified by pathogen whenever sample size allowed. Findings: We included 2216 children with a history of bacterial meningitis (570 [25·7%] in Denmark between Jan 1, 1997, and Dec 31, 2018, and 1646 [74·3%] in the Netherlands between Jan 1, 1995, and Dec 31, 2018), matched to 22 127 comparison cohort members. Median age at diagnosis was 2·8 months (IQR 0·4–7·1) in Denmark and 4·3 months (0·7–7·4) in the Netherlands. Mortality risks within 3 months after disease onset were 3·9% (95% CI 2·6–5·8%) in Denmark and 5·9% (4·7–7·0) in the Netherlands, compared with 0·0% (p<0·0001) and 0·1% (p<0·0001) in the comparison cohorts. Survivors had an increased risk of moderate or severe NDIs at age 10 years (RR 5·0 [95% CI 3·5–7·1] in Denmark and 4·9 [4·0–6·2] in the Netherlands) compared to children in the comparison cohort, particularly after pneumococcal and group B streptococcal meningitis. In Denmark, a history of bacterial meningitis was associated with increased health-care use in the 10 years following diagnosis (rate ratio 4·5 [95% CI 3·9–5·2] for outpatient visits and 4·1 [3·6–4·7] for hospital admissions). Interpretation: Our study shows increased risk of mortality in the short and long term, a five times increase in risk of NDIs, and increased health-care use after bacterial meningitis during infancy. Together with context-specific incidence data, our results can advance pathogen-specific estimation of the meningitis burden and inform service provision at the individual and population level. Funding: Bill & Melinda Gates Foundation, the Stichting Remmert Adriaan Laan Fonds, and the Netherlands Organisation for Health Research and Development.

AB - Background: Few studies have reported the long-term consequences of bacterial meningitis during infancy, and studies that have been done usually do not include a comparison cohort. We aimed to assess short-term and long-term risk of mortality, neurodevelopmental impairment (NDI), and health-care use and household income in cohorts of children with and without a history of bacterial meningitis during infancy in Denmark and the Netherlands. Methods: In this nationwide cohort study, infants with a history of bacterial meningitis before age 1 year were identified through the Danish Medical Birth Registry and Danish National Patient Registry using International Classification of Diseases (ICD)-10 codes and through the Netherlands Reference Laboratory for Bacterial Meningitis. Infants were matched (1:10) by sex and birth month and year to a comparison cohort of the general population without a history of bacterial meningitis. We analysed mortality using Cox proportional hazards regression. In Denmark, diagnoses of NDIs were based on ICD-10 codes; in the Netherlands, special educational needs were used as a functional NDI outcome. Risk ratios (RRs) of NDIs were estimated using modified Poisson regression. We also analysed long-term health-care use in Denmark and household income in both countries. All regression analyses were adjusted for sex and year of birth, and stratified by pathogen whenever sample size allowed. Findings: We included 2216 children with a history of bacterial meningitis (570 [25·7%] in Denmark between Jan 1, 1997, and Dec 31, 2018, and 1646 [74·3%] in the Netherlands between Jan 1, 1995, and Dec 31, 2018), matched to 22 127 comparison cohort members. Median age at diagnosis was 2·8 months (IQR 0·4–7·1) in Denmark and 4·3 months (0·7–7·4) in the Netherlands. Mortality risks within 3 months after disease onset were 3·9% (95% CI 2·6–5·8%) in Denmark and 5·9% (4·7–7·0) in the Netherlands, compared with 0·0% (p<0·0001) and 0·1% (p<0·0001) in the comparison cohorts. Survivors had an increased risk of moderate or severe NDIs at age 10 years (RR 5·0 [95% CI 3·5–7·1] in Denmark and 4·9 [4·0–6·2] in the Netherlands) compared to children in the comparison cohort, particularly after pneumococcal and group B streptococcal meningitis. In Denmark, a history of bacterial meningitis was associated with increased health-care use in the 10 years following diagnosis (rate ratio 4·5 [95% CI 3·9–5·2] for outpatient visits and 4·1 [3·6–4·7] for hospital admissions). Interpretation: Our study shows increased risk of mortality in the short and long term, a five times increase in risk of NDIs, and increased health-care use after bacterial meningitis during infancy. Together with context-specific incidence data, our results can advance pathogen-specific estimation of the meningitis burden and inform service provision at the individual and population level. Funding: Bill & Melinda Gates Foundation, the Stichting Remmert Adriaan Laan Fonds, and the Netherlands Organisation for Health Research and Development.

KW - Child

KW - Cohort Studies

KW - Denmark/epidemiology

KW - Humans

KW - Infant

KW - Meningitis, Bacterial/complications

KW - Netherlands/epidemiology

KW - Streptococcus pneumoniae

UR - http://www.scopus.com/inward/record.url?scp=85136341881&partnerID=8YFLogxK

U2 - 10.1016/S2352-4642(22)00155-9

DO - 10.1016/S2352-4642(22)00155-9

M3 - Article

C2 - 35798010

VL - 6

SP - 633

EP - 642

JO - The Lancet Child and Adolescent Health

JF - The Lancet Child and Adolescent Health

SN - 2352-4642

IS - 9

ER -