母亲抗生素暴露与儿童四岁时情绪和行为问题的关联：基于生物监测的前瞻性研究。
Association between maternal antibiotic exposure and emotional and behavioural problems in children at four years of age: A biomonitoring-based prospective study.
机构信息
School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China.
School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui 230032, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui 230032, China; Anhui Provincial Key Laboratory of Environment and Population Health across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China; Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China.
出版信息
Ecotoxicol Environ Saf. 2024 Oct 1;284:116949. doi: 10.1016/j.ecoenv.2024.116949. Epub 2024 Aug 28.
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.
背景
母体在孕期接触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有限。
方法
本研究共纳入了 2475 名来自马鞍山出生队列的孕妇，当她们的孩子四岁时完成了《长处和困难问卷》。在孕早期、孕中期和孕晚期分别检测了 41 种母体尿液抗生素及其两种代谢物的水平。采用广义估计方程和二项逻辑回归模型分析了母体抗生素暴露与儿童情绪和行为问题之间的关系，并确定了敏感时期。基于分位数的广义计算（QGC）方法用于检验多种抗生素对儿童情绪和行为问题的联合效应。
结果
总体而言，氟苯尼考和兽用抗生素（PVA）在孕期的暴露增加了儿童情绪问题的风险，氧氟沙星暴露增加了多动注意力不集中的风险。孕早期母体暴露于甲氧苄啶、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，孕早期混合抗生素暴露增加了儿童情绪问题的风险（环丙沙星的贡献较为显著），孕中期混合抗生素暴露增加了多动注意力不集中的风险（甲氧苄啶的贡献较为显著）。
结论
母体在孕早期和孕中期混合抗生素暴露增加了儿童在四岁时出现情绪问题和多动注意力不集中的风险。
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