母亲怀孕期间接触环境抗生素，可能增加子女学龄前期情绪行为问题发生风险

Prenatal antibiotics exposure and preschoolers’ internalizing and externalizing problems: A biomonitoring-based prospective birth cohort study

产前抗生素暴露与学龄前儿童内外化行为问题：一项基于生物监测的前瞻性出生队列研究

Author: Menglong Geng, Peng Ding, Sheng Wang, Baolin Wang, Juan Tong, Hui Gao, Shuangqin Yan, Kaiyong Liu, Xiaoyan Wu, Peng Zhu, Yunxia Cao, Kun Huang, Fangbiao Tao

Source: Science of the Total Environment

DOI: 10.1016/j.scitotenv.2024.170891.

Abstract

Background: Biomonitoring-based epidemiological studies on prenatal antibiotic exposure and behavioral problems in preschoolers are lacking.The present study aimed to investigate the relationship between prenatal antibiotic exposure and internalizing and externalizing problems in preschoolers.

Methods: Data from 2449 mother–child pairs were analyzed. Urine samples were repeatedly collected across three trimesters, and 43 antibiotics and 2 metabolites were measured, including preferred as veterinary antibiotics (PVAs), VAs, preferred as human antibiotics and human antibiotics. Preschoolers’ internalizing and externalizing problems were evaluated by the Achenbach Child Behavior Checklist. Poisson regression models with generalized estimating equations were used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for preschoolers’ internalizing, externalizing and total problems across tertiles of antibiotic concentrations during three periods of pregnancy, and performed several subgroup analyses.

Results: First-trimester urinary oxytetracycline (RR=1.69, 95%CI: 1.20, 2.39, P-_FDR=0.011), tetracycline (RR=1.91, 95%CI: 1.36, 2.68, P-_FDR<0.001), doxycycline (RR=1.66, 95%CI: 1.28, 2.17, P-_FDR<0.001) and PVAs (RR=1.79, 95%CI: 1.29, 2.48, P-_FDR<0.001) concentrations in the highest tertile were related to an elevated risk of internalizing problems compared with concentrations in the lowest tertile. First-trimester urinary doxycycline concentrations in the third tertile were also associated with an increased risk of externalizing problems compared with the first tertile (RR=2.00, 95%CI: 1.28, 3.15, P-_FDR=0.042). Compared with concentrations in the lowest tertile, first-trimester urinary doxycycline (RR=1.63, 95%CI: 1.19, 2.22, P-_FDR=0.028) and PVAs (RR=1.67, 95%CI: 1.14, 2.43, P-_FDR=0.047) concentrations in the middle tertile were related to an increased risk of total problems. Furthermore, the type of main caregiver and children’s outdoor activities time modified the relationships between specific prenatal antibiotic exposure and preschoolers’ behavioral problems.

Conclusions: Exposure to specific antibiotics during the first trimester may be related to an increased risk of internalizing and externalizing problems in preschoolers.

Keywords: Antibiotics; Biomonitoring; Urine biomarkers; Prenatal exposure; Behavioral problems; Birth cohort

摘要

背景: 目前尚无基于生物监测的产前抗生素暴露与儿童心理行为问题的流行病学研究。当前研究旨在分析产前抗生素暴露与学龄前儿童内外化行为问题之间的关联。

方法: 本研究纳入2449对母子，在三个孕期均收集了孕妇尿液样本，并检测包括优先兽用抗生素（PVAs），兽用抗生素、优先人用抗生素和人用抗生素在内的43种抗生素（包括2种代谢物），同时使用阿肯巴克儿童行为量表评估学龄前儿童内外化行为问题。基于广义估计方程的Poisson回归模型计算相对危险度（RRs）及其95%置信区间（CI），用以评估产前不同浓度抗生素暴露与学龄前儿童内外化行为问题的关联强度。此外，本研究还进行了一系列亚组分析。 

结果: 与最低浓度暴露组相比，孕妇在孕早期暴露于最高浓度的土霉素（RR=1.69, 95%CI: 1.20～2.39, P-_FDR=0.011）、四环素（RR=1.91, 95%CI: 1.36～2.68, P-_FDR<0.001）、多西环素（RR=1.66, 95%CI: 1.28～2.17, P-_FDR<0.001）和PVAs（RR=1.79, 95%CI: 1.29～2.48, P-_FDR<0.001）会增加其子代学龄前期内化行为问题的发生风险，暴露于最高浓度多西环素（RR=2.00, 95%CI: 1.28～3.15, P-_FDR=0.042）与学龄前儿童外化行为问题发生风险增加相关，而暴露于中等浓度的多西环素（RR=1.63, 95%CI: 1.19, 2.22, P-_FDR=0.028）和PVAs （RR=1.67, 95%CI: 1.14, 2.43, P-_FDR=0.047）会增加学龄前儿童总体行为问题的发生风险。此外，儿童主要带养人和户外活动时间在上述关联中起到修饰作用。

结论: 产前暴露于特定抗生素会增加学龄前儿童内外化行为问题的发生风险。