生命早期抗生素暴露与儿童健康的流行病学研究进展

Epidemiological research advances on antibiotic exposure in early life and child health

生命早期是儿童生长发育的关键窗口期,但这一精妙而复杂的时期极易受到各种外源性化学物质干扰,进而对个体健康状况造成短期或长期不良影响。抗生素的大量使用导致其在生命早期就已普遍暴露,同时可能会对儿童的健康结局造成不利影响,当前已引起公共卫生领域的高度关注。本文总结近年来生命早期抗生素暴露的人群流行现况及其与儿童生长发育、过敏及心理行为问题等健康结局关联的流行病学研究,并进一步介绍上述关联潜在的生物学机制。当前流行病学研究结果提示包括孕期和婴幼儿期在内的生命早期抗生素暴露与儿童过敏性疾病(如特应性皮炎、哮喘等)、生长发育(如肥胖、出生身长等)和儿童心理行为问题(如自闭症、焦虑症等)等关联密切,肠道菌群、甲状腺功能、炎症因子、线粒体功能以及表观遗传等可能是联结生命早期抗生素暴露和儿童健康的潜在生物学机制。未来研究应依托大样本的前瞻性出生队列,在生命早期多时点收集生物学样本,测定其中不同类型抗生素的内暴露水平并分析其与儿童健康结局的关联,同时进一步开展相关的生物学机制研究,为生命早期环境暴露儿童健康效应领域提供高质量研究证据。

Early life is a critical window period that determines the growth and development of children,but this delicate and complex period is highly susceptible to the disturbance of various exogenous chemicals,which in consequence may lead to short-term or long-term adverse health effects in human beings.The massive use of antibiotics has contributed to widespread exposure in early life,along with the potentially adverse effects on child health,and has caused great concern in public health.This review summarized recent epidemiological studies on the population with early-life antibiotic exposure and associated health outcomes such as growth and development,allergies,and psycho-behavioral problems in children,as well as potential biological mechanisms underlying these associations.Current findings suggested that antibiotic exposure early in life,including pregnancy and infancy,is strongly associated with childhood allergic diseases(e.g.,atopic dermatitis and asthma),growth and development(e.g.,obesity and birth length),and childhood psycho-behavioral problems(e.g.,autism and anxiety).It also suggested that antibiotic exposure may affect individual health through gut microbiota,thyroid function,inflammation factors,mitochondrial function,and epigenetic mechanisms.In the future,more large prospective birth cohorts should be established to determine the levels of internal exposure to different types of antibiotics at multiple time points in early life and to explore their associations with child health outcomes,as well as to further validate relevant mechanisms,aiming to provide high-quality scientific evidence for research on child health associated with environmental exposure in early life.