Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark.
Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Lancet Child Adolesc Health. 2021 Jun;5(6):398-407. doi: 10.1016/S2352-4642(21)00022-5. Epub 2021 Apr 21.
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.
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.
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.
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.
The Bill & Melinda Gates Foundation.
For the Dutch and Danish translations of the abstract see Supplementary Materials section.
B 群链球菌（GBS）疾病是导致新生儿死亡的主要原因，但在儿童早期之后，其长期影响尚未得到研究。本研究的目的是评估丹麦和荷兰的侵袭性 B 群链球菌（iGBS）疾病在婴儿期至青春期后导致的长期死亡率、神经发育障碍（NDIs）和经济结果。
为了进行这项队列研究，我们在丹麦和荷兰使用国家医疗和行政数据库以及培养结果来确定患有 iGBS 疾病的儿童。患有 iGBS 疾病的儿童被定义为在 89 天龄时患有败血症、脑膜炎或肺炎。对于每个患有 iGBS 疾病的儿童，我们随机选择了 10 名未患有 iGBS 疾病的儿童，并按照性别、出生年月和胎龄进行匹配。我们使用 Cox 比例风险模型分析死亡率数据。在丹麦，我们从国家患者登记处（丹麦）的出院诊断中获取了青春期前的神经发育障碍数据；在荷兰，我们从特殊教育支持记录中获取了青春期前的神经发育障碍数据。我们还比较了暴露组和未暴露组的医疗保健使用情况和家庭收入。
我们确定了 2258 名儿童（1561 名在丹麦出生，1997 年 1 月 1 日至 2017 年 12 月 31 日；697 名在荷兰出生，2000 年 1 月 1 日至 2017 年 12 月 31 日）患有 iGBS 疾病，并对其进行了中位随访 14 年（丹麦为 7-18 年，荷兰为 6-11 年）。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 22462 名无 iGBS 疾病史的儿童进行了匹配。iGBS 脑膜炎与 5 岁时的死亡率增加有关（丹麦的调整后的危险比为 4.08 [95%CI 1.78-9.35]，荷兰为 6.73 [3.76-12.06]）。任何 iGBS 疾病都与 10 岁时发生 NDIs 的风险增加有关，无论是在丹麦（风险比为 1.77 [95%CI 1.44-2.18]）还是在荷兰（风险比为 2.28 [1.64-3.17]）。患有 iGBS 疾病的儿童在 5 岁或以下时，门诊就诊（发病率比为 1.93 [95%CI 1.79-2.09]，p<0.0001）和住院治疗（1.33 [1.27-1.38]，p<0.0001）的频率更高。暴露组和未暴露组的家庭收入没有差异。
iGBS 疾病，特别是脑膜炎，与儿童期后期的死亡率增加和神经发育障碍风险增加有关。这一以前未被量化的负担强调了需要一种针对母体 GBS 的疫苗，并需要对 iGBS 疾病的幸存者进行跟踪和提供关怀。
比尔及梅琳达·盖茨基金会。
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