Background

Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands.

Methods

For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts.

Findings

2258 children—1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)—were identified to have iGBS disease and followed up for a median of 14 years (IQR 7–18) in Denmark and 9 years (6–11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78–9·35] for Denmark and 6·73 [3·76–12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44–2·18]) and the Netherlands (2·28 [1·64–3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79–2·09], p<0·0001) and hospital admissions (1·33 [1·27–1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts.

Interpretation

iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease.

Funding

The Bill & Melinda Gates Foundation.

Translations

For the Dutch and Danish translations of the abstract see Supplementary Materials section.

中文翻译：

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丹麦和荷兰婴儿期早期侵袭性B组链球菌感染后的死亡率，神经发育障碍和经济结果：一项全国匹配队列研究

背景

B组链球菌（GBS）疾病是新生儿死亡的主要原因，但其长期影响尚未在儿童早期就得到研究。本研究的目的是评估丹麦和荷兰的婴儿浸润性GBS（iGBS）疾病直至青春期后的长期死亡率，神经发育障碍（NDI）和经济结果。

方法

在这项队列研究中，使用国家医学和行政数据库以及证实其诊断的培养结果，在丹麦和荷兰鉴定出患有iGBS疾病的儿童。暴露儿童被定义为到89天时有iGBS病史（败血症，脑膜炎或肺炎）。对于每个暴露的孩子，随机选择十个未暴露的孩子，并按性别，出生年份和月份以及胎龄进行匹配。使用Cox比例风险模型分析了死亡率数据。直到青春期的NDI数据都是从国家病人登记处（丹麦）和特殊教育支持记录（荷兰）中的出院诊断中获取的。还比较了暴露人群和未暴露人群的医疗保健使用和家庭收入。

发现

确认2258名儿童（其中丹麦（出生于1997年1月1日至2017年12月31日）的1561名儿童和荷兰（出生于2000年1月1日至2017年12月31日）的697名儿童患有iGBS疾病，并进行了中位随访丹麦的14年（IQR 7-18）和荷兰的9年（6-11）。366名儿童患有脑膜炎，1763名患有败血症，129名患有肺炎（仅在丹麦）。这些儿童与22 462名无iGBS病史的儿童相匹配。iGBS脑膜炎与5岁时死亡率增加有关（丹麦的危险比调整为4·08 [95％CI 1·78-9·35]，荷兰为6·73 [3·76-12·06]） 。在丹麦（风险比1·77 [95％CI 1·44-2·18]）和荷兰（2·28 [1·64]），任何iGBS疾病都与10岁以下的NDI风险增加有关。 –3·17]）。有iGBS病史与门诊就诊频率更高（发生率比率1·93 [95％CI 1·79-2·09]，p <0·0001）和住院次数（1·33 [1·27] –1·38]，p <0·0001）在5岁以下的儿童中。暴露人群和未暴露人群之间的家庭收入没有差异。

解释

iGBS疾病，特别是脑膜炎，与儿童后期死亡率增加和NDI发生风险增加有关。先前无法量化的负担突显了孕妇GBS疫苗的情况，以及对iGBS疾病幸存者进行跟踪和提供护理的需求。

资金

比尔和梅琳达·盖茨基金会。

笔译

有关摘要的荷兰语和丹麦语翻译，请参见“补充材料”部分。