母亲在妊娠早期和中期接触多种抗生素可能会增加四岁儿童的情绪和行为问题风险

Association between maternal antibiotic exposure and emotional and behavioural problems in children at four years of age:

A biomonitoring-based prospective study

母亲抗生素暴露与四岁儿童情绪和行为问题的关联：一项基于生物监测的前瞻性研究

Authors: Wanhong Xiong, Baolin Wang, Feifei Han, Juan Tong, Hui Gao, Peng Ding, Kaiyong Liu, Xiaoyan Wu, Kun Huang Menglong Geng, Fangbiao Tao

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2024.116949.

Abstract

Background: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited.

Methods: A total of 2475 pregnant women from the Ma’anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children.

Results: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). 

Conclusion: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age. 

Keywords: Antibiotics; Biomonitoring; Emotional and behavioural problems; Children

摘要 

背景：孕妇在怀孕期间暴露于多种抗生素已引起广泛关注，但将产前抗生素暴露与儿童情绪和行为问题联系起来的生物监测研究却很有限。

方法：在马鞍山出生队列中共纳入2475 名孕妇，并在其子女四岁时完成了优势和困难问卷调查。在妊娠早期、中期和晚期检测了41种母亲尿中抗生素和两种代谢物的水平。采用广义估计方程和二元logistic回归模型分别分析了母亲的抗生素暴露与儿童情绪和行为问题之间的关联，并确定了敏感期。采用基于分位数的g计算（QGC）方法来研究多种抗生素对儿童情绪和行为问题的综合影响。

结果：总体而言，孕期接触氟苯尼考和首选兽用抗生素（PVA）会增加儿童出现情绪问题的风险，而接触氧氟沙星会增加多动-注意力不集中的风险。母亲在孕早期接触甲氧苄啶、环丙沙星、氟苯尼考、其他抗生素和PVA与儿童的情绪问题呈正相关。孕中期甲氧苄啶浓度和孕晚期环丙沙星浓度与多动-注意力不集中呈正相关。孕晚期兽用抗生素（VA）暴露与多动-注意力不集中呈负相关，孕中期VA和PVA暴露与同伴问题呈负相关。QGC模型显示，孕早期的混合抗生素暴露会增加儿童情绪问题的风险（环丙沙星的贡献突出），而孕中期的混合抗生素暴露会增加多动-注意力不集中的风险（甲氧苄啶的贡献突出）。

结论：母亲在孕早期和孕中期的混合抗生素暴露会增加4岁儿童出现情绪问题和多动-注意力不集中的风险。

关键词：抗生素；生物监测；情绪和行为问题；儿童