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.

中文翻译：

---

丹麦和荷兰儿童在婴儿期细菌性脑膜炎后死亡和神经发育障碍的短期和长期风险：一项全国匹配的队列研究

背景

很少有研究报告婴儿期细菌性脑膜炎的长期后果，并且已经完成的研究通常不包括对照组。我们旨在评估丹麦和荷兰婴儿期有和没有细菌性脑膜炎病史的儿童队列的短期和长期死亡率、神经发育障碍 (NDI) 以及医疗保健使用和家庭收入风险。

方法

在这项全国性队列研究中，通过丹麦医学出生登记处和丹麦国家患者登记处使用国际疾病分类 (ICD)-10 代码和荷兰细菌性脑膜炎参考实验室确定了 1 岁之前有细菌性脑膜炎病史的婴儿. 将婴儿按性别、出生月份和年份与没有细菌性脑膜炎病史的普通人群进行比较（1:10）。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 代码；在荷兰，特殊教育需求被用作功能性 NDI 结果。使用改进的泊松回归估计 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。

发现

我们纳入了 2216 名有细菌性脑膜炎病史的儿童（1997 年 1 月 1 日至 2018 年 12 月 31 日期间在丹麦有 570 名 [25·7%]，在 1995 年 1 月 1 日期间在荷兰有 1646 名 [74·3%]，以及2018 年 12 月 31 日），与 22 127 名比较队列成员​​匹配。诊断时的中位年龄在丹麦为 2·8 个月（IQR 0·4-7·1），在荷兰为 4·3 个月（0·7-7·4）。发病后 3 个月内的死亡风险在丹麦为 3·9% (95% CI 2·6–5·8%)，在荷兰为 5·9% (4·7–7·0)，而在荷兰为 0·在比较组中为 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 RR 5·0 [95% CI 3·5-7·1]，荷兰 4·9 [4·0-6·2]）与对照组中的儿童相比，特别是在肺炎球菌和 B 组链球菌脑膜炎之后。在丹麦，

解释

我们的研究表明，短期和长期死亡风险增加，NDI 风险增加五倍，婴儿期细菌性脑膜炎后医疗保健使用增加。结合特定背景的发病率数据，我们的结果可以促进对脑膜炎负担的特定病原体估计，并为个人和人群水平的服务提供提供信息。

资金

比尔和梅琳达盖茨基金会、Stichting Remmert Adriaan Laan Fonds 和荷兰卫生研究与发展组织。