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产前抗生素暴露与学龄前儿童注意缺陷多动障碍症状的关联:维生素 D 母体的作用。

Associating prenatal antibiotics exposure with attention deficit hyperactivity disorder symptoms in preschool children: The role of maternal vitamin D.

机构信息

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; Anhui Provincial Key Laboratory of Environment and Population Health across the Life Course, 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; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (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.

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, Anhui 230022, China.

出版信息

Ecotoxicol Environ Saf. 2024 Oct 15;285:117037. doi: 10.1016/j.ecoenv.2024.117037. Epub 2024 Sep 12.

DOI:10.1016/j.ecoenv.2024.117037
PMID:39270477
Abstract

BACKGROUND

The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored.

OBJECTIVES

To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D.

METHODS

Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status.

RESULTS

Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester.

CONCLUSIONS

Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

摘要

背景

产前抗生素暴露与学龄前儿童注意缺陷多动障碍(ADHD)之间的关系,以及母体维生素 D 在这些关系中的作用,仍有待探索。

目的

评估多种母体尿液抗生素水平与学龄前儿童 ADHD 症状之间的关系,并确定母体维生素 D 的潜在调节作用。

方法

基于一项前瞻性出生队列研究,本研究纳入了 2033 对母婴。在整个孕期的三个阶段采集了母体尿液和血清样本,以测量 43 种抗生素(包括两种代谢物)的尿液浓度和血清维生素 D 水平。使用 Achenbach 儿童行为检查表中的诊断和统计手册导向的 ADHD 问题量表评估学龄前儿童的 ADHD 症状。采用多 informant 模型的逻辑回归分析方法,调查产前抗生素暴露与学龄前儿童 ADHD 症状之间的关系,并根据儿童性别和母体维生素 D 状况对这些关系进行分层。

结果

与最低三分位浓度相比,母亲在孕早期接触中三分位浓度的强力霉素和人类抗生素/首选人类抗生素(HAs/PHAs)以及最高三分位浓度的强力霉素与儿童 ADHD 症状的风险增加相关。在孕中期接触最高三分位浓度的磺胺甲噁唑的女孩,ADHD 症状的风险增加。此外,维生素 D 缺乏的孕妇在孕早期接触强力霉素后,其子女患 ADHD 症状的风险增加。

结论

母亲在孕早期接触强力霉素和 HAs/PHAs 会增加学龄前儿童 ADHD 症状的风险。孕中期接触磺胺甲噁唑会增加女孩 ADHD 症状的风险。妊娠期间母体维生素 D 缺乏可能会加剧强力霉素暴露对 ADHD 症状的不良影响。

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