School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, 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 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, 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 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
Ecotoxicol Environ Saf. 2021 Dec 1;225:112736. doi: 10.1016/j.ecoenv.2021.112736. Epub 2021 Sep 1.
Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing.
This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age.
The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children.
The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children.
Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.
基于病历或问卷调查方法，先前的流行病学研究已经调查了母亲在怀孕期间使用抗生素与儿童过敏性疾病之间的关联。然而，有关产前低剂量抗生素暴露的生物监测研究（主要来自环境和受污染的食物）与儿童过敏性疾病之间的关系尚属空白。
本研究旨在检验多次测量的产前低剂量抗生素暴露与 4 岁儿童当前过敏性疾病之间的关联。
本研究包括 2453 对母婴对，基于马鞍山出生队列研究。通过液相色谱-三重四极杆串联质谱法，在 2453 名孕妇的尿液样本中对 41 种抗生素及其两种代谢物（包括人用抗生素（HAs）、首选人用抗生素（PHAs）、兽用抗生素（VAs）和首选兽用抗生素（PVAs））进行了生物监测。通过经过验证的调查问卷收集了儿童当前过敏疾病的信息。使用广义估计方程来探讨母亲在妊娠三个 trimester 期间尿液中抗生素的重复测量值与儿童当前过敏疾病之间的关系。
在怀孕期间的三个 trimester 中，有九种单独抗生素的检出率大于 10%，检出抗生素的 90 百分位浓度范围为 0.07-22.34μg/g，95 百分位浓度范围为 0.17-59.57μg/g。在参与者中，第一 trimester 中磺胺甲恶唑（调整后的 OR=1.28，95%CI：1.10，1.49，P-=0.014）和第二 trimester 中环丙沙星（调整后的 OR=1.17，95%CI：1.07，1.28，P-=0.008）的浓度每增加一个单位，与儿童当前湿疹的风险增加相关。在第三个 trimester 中，土霉素（调整后的 OR=1.90，95%CI：1.30，2.78，P-=0.014）的浓度每增加一个单位与儿童当前哮喘的风险增加相关。性别分层分析表明，产前抗生素暴露与儿童当前过敏疾病之间的关联在性别上没有差异。
母体在不同 trimester 中暴露于某些特定的 VAs 或 PVAs（磺胺甲恶唑、环丙沙星和土霉素）与 4 岁儿童当前哮喘和当前湿疹的风险增加有关。在这些关联中没有发现性别差异。需要进一步的研究来证实我们的发现并探索潜在的机制。
