孕期不同维生素D水平能够调节产前抗生素暴露对学龄前儿童ADHD症状的影响

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关联：母体维生素D的调节作用

Author: 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.

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

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: 评估母体尿液中多种抗生素暴露水平与学龄前儿童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: 基于马鞍山优生优育队列，本研究纳入了2033对母子作为研究对象。研究收集了三个孕期的母体尿液和血清样本，以测量尿液中 43 种抗生素（包括两种代谢物）的浓度和血清中维生素D的水平。学龄前儿童的多动症状采用儿童行为量表（CBCL）中的ADHD维度进行评估。采用多信息模型（以Logistic回归形式）来研究产前抗生素暴露与学龄前儿童ADHD症状之间的关联，并根据儿童性别和母亲的维生素D状态进行分层分析。 

结果: 与最低浓度相比，母亲在孕早期接触中等浓度的强力霉素和人类抗生素/首选人类抗生素（HAs/PHAs）以及最高浓度的强力霉素与儿童ADHD症状风险增加有关。在孕中期暴露于最高浓度的磺胺二甲基嘧啶的女童中，出现多动症症状的风险也有所增加。此外，孕期缺乏维生素D的孕妇在孕早期接触强力霉素后，其后代出现ADHD症状的风险更大。

结论: 母亲在孕早期暴露于强力霉素和HAs/PHAs会增加学龄前儿童出现ADHD症状的风险。孕中期接触磺胺二甲基嘧啶会增加女童出现ADHD症状的风险。孕妇在怀孕期间缺乏维生素 D可能会加剧接触强力霉素对子代ADHD症状的影响。