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

产前抗生素暴露与学龄前儿童注意缺陷多动障碍症状的相关性：母体维生素D的作用

Authors: Menglong Geng, Zhen Yu, Baolin Wang, Wanhong Xiong, Guanlin Sang, Yunfeng Song, Juan Tong, Hui Gao, Peng Ding, Kaiyong Liu, Xiaoyan Wu, Kun Huang, Fangbiao Tao.

Source: Ecotoxicol Environ Saf. 2024 Sep 12:285:117037.

doi: 10.1016/j.ecoenv.2024.117037. 

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.

Keywords: Antibiotics; Attention-deficit/hyperactivity disorder; Biomonitoring; Birth cohort; Prenatal exposure.

摘要

背景：产前抗生素暴露与学龄前儿童注意力缺陷/多动障碍（ADHD）之间的关联，以及母体维生素D在这些关联中的作用，仍有待探讨。

目的： 评价母体多种尿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的潜在修饰作用。

方法：基于前瞻性出生队列，本研究包括2 033对母子。在所有三个孕早期收集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Achenbac儿童行为检查表中面向诊断和统计手册的ADHD问题量表评估学龄前儿童ADHD症状。以逻辑回归的形式进行多个知情人模型，以调查产前抗生素暴露与学龄前ADHD症状之间的关联，这些关联按儿童性别和母体维生素D状况分层。

结果：与最低三分位数浓度相比，产妇暴露于中等三分位数浓度的多西环素和人抗生素/首选人抗生素（HAs/PHA），以及妊娠早期多西环素的最高三分位数浓度与儿童ADHD症状的风险增加相关。在妊娠中期暴露于最高三分水平磺胺二甲嘧啶的女孩中观察到ADHD症状的风险增加。此外，维生素D缺乏症的孕妇在妊娠早期接触多西环素后，其后代出现ADHD症状的风险更大。

结论：母亲在妊娠早期暴露于多西环素和HAs/PHAs会增加学龄前儿童ADHD 症状的风险。怀孕中期接触磺胺二甲嘧啶会增加女孩出现ADHD症状的风险。母亲在怀孕期间缺乏维生素D可能会加剧多西环素暴露对ADHD症状的不利影响。

关键词：抗生素；注意力缺陷/多动障碍；生物监测；出生队列；产前暴露