Department of Neurology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Neuroscience, Neuroinfection and Inflammation, Amsterdam, Netherlands.
Maternal, Adolescent, Reproductive and Child Health Centre and Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Child Adolesc Health. 2022 Sep;6(9):633-642. doi: 10.1016/S2352-4642(22)00155-9. Epub 2022 Jul 5.
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.
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.
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).
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.
Bill & Melinda Gates Foundation, the Stichting Remmert Adriaan Laan Fonds, and the Netherlands Organisation for Health Research and Development.
很少有研究报告婴儿期细菌性脑膜炎的长期后果，而且已有的研究通常不包括对照队列。我们旨在评估丹麦和荷兰有和无婴儿期细菌性脑膜炎病史的两组儿童的短期和长期死亡率、神经发育障碍（NDI）风险、医疗保健使用和家庭收入。
在这项全国性队列研究中，通过丹麦医疗出生登记处和丹麦国家患者登记处，使用国际疾病分类（ICD）第 10 版编码，并通过荷兰细菌性脑膜炎参考实验室，确定了 1 岁前患有细菌性脑膜炎的婴儿。通过性别和出生月份及年份与无细菌性脑膜炎病史的一般人群的对照队列进行 1:10 匹配。我们使用 Cox 比例风险回归分析死亡率。在丹麦，NDI 的诊断基于 ICD-10 编码；在荷兰，特殊教育需求被用作功能性 NDI 结果。使用改良泊松回归估计 NDI 的风险比（RR）。我们还分析了丹麦的长期医疗保健使用情况和两国的家庭收入。所有回归分析均调整了性别和出生年份，并根据病原体大小进行分层（在样本量允许的情况下）。
我们纳入了 2216 名患有细菌性脑膜炎的儿童（1997 年 1 月 1 日至 12 月 31 日期间丹麦有 570 名[25.7%]，1995 年 1 月 1 日至 12 月 31 日期间荷兰有 1646 名[74.3%]），并与 22127 名对照队列成员进行了匹配。丹麦的中位诊断年龄为 2.8 个月（0.4-7.1），荷兰为 4.3 个月（0.7-7.4）。在疾病发作后 3 个月内，丹麦的死亡率风险为 3.9%（95%CI 2.6-5.8%），荷兰为 5.9%（4.7-7.0%），而对照队列中为 0.0%（p<0.0001）和 0.1%（p<0.0001）。幸存者在 10 岁时发生中度或重度 NDI 的风险增加（丹麦为 5.0[95%CI 3.5-7.1]，荷兰为 4.9[4.0-6.2]），与对照队列中的儿童相比，尤其是在发生肺炎球菌和 B 组链球菌脑膜炎后。在丹麦，细菌性脑膜炎与诊断后 10 年内医疗保健使用增加有关（门诊就诊的发生率比为 4.5[95%CI 3.9-5.2]，住院就诊的发生率比为 4.1[3.6-4.7]）。
我们的研究表明，在短期和长期，死亡率风险增加，神经发育障碍风险增加 5 倍，婴儿期细菌性脑膜炎后医疗保健使用增加。结合特定病原体的发病数据，我们的结果可以推进针对特定病原体的脑膜炎负担估计，并为个人和人群层面的服务提供信息。
比尔及梅琳达·盖茨基金会、雷默特·阿德瑞安·拉恩基金会和荷兰健康研究与发展组织。
