Geng Menglong, Gao Hui, Wang Baolin, Huang Kun, Wu Xiaoyan, Liang Chunmei, Yan Shuangqin, Han Yan, Ding Peng, Wang Wei, Wang Sheng, Zhu Peng, Liu Kaiyong, Cao Yunxia, Tao Fangbiao
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.
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; Anhui Provincial Institute of Translational Medicine, No 81 Meishan Road, Hefei 230032, Anhui, China; Department of Pediatric, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, China.
Sci Total Environ. 2022 Sep 10;838(Pt 2):156146. doi: 10.1016/j.scitotenv.2022.156146. Epub 2022 May 21.
Studies on potential maternal thyrotoxicity related to tetracycline antibiotics exposure during pregnancy are lacking. Based on a large prospective cohort study, this study aimed to examine the associations between tetracycline antibiotics exposure in maternal urine and maternal thyroid hormone parameters.
Based on the Ma'anshan Birth Cohort study, urine and serum samples of 2969 pregnant women were collected in the first, second and third trimesters. Tetracycline antibiotics, including oxytetracycline, chlorotetracycline, tetracycline and doxycycline in urine samples, as well as free thyroxine (FT4), thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels in serum samples, were measured. Linear mixed models and multivariate linear regression models were employed to examine associations between tetracycline antibiotics exposure during pregnancy and maternal thyroid hormone parameters.
The detection rates of four individual tetracycline antibiotics and all antibiotics (sum of four individual tetracycline antibiotics) in the three trimesters were 5.0%-52.3%, and the 95th percentile concentration ranged from 0.11 to 4.84 ng/mL. After adjusting for potential confounding factors, the repeated measures analyses indicated that pregnant women exposed to doxycycline and all antibiotics during the entire pregnancy were negatively associated with serum FT4 and TT4 levels but positively associated with serum TSH and TT3 levels. Trimester-stratified analyses found that doxycycline and all antibiotics exposure during the first trimester were negatively associated with serum FT4 and TT4 levels, while doxycycline was positively associated with TSH levels. In the third trimester, a significant association was only found between all antibiotics and TSH levels.
Our results suggest that exposure of pregnant women to tetracycline antibiotics is associated with maternal thyroid hormone parameters, and the first trimester might be the most critical window. More studies are needed to substantiate our findings and determine the underlying biological mechanisms.
关于孕期接触四环素类抗生素与潜在母体甲状腺毒症的研究尚缺。基于一项大型前瞻性队列研究，本研究旨在探讨母体尿液中四环素类抗生素暴露与母体甲状腺激素参数之间的关联。
基于马鞍山出生队列研究，收集了2969名孕妇在孕早期、孕中期和孕晚期的尿液和血清样本。检测尿液样本中的土霉素、金霉素、四环素和强力霉素等四环素类抗生素，以及血清样本中的游离甲状腺素（FT4）、促甲状腺激素（TSH）、总三碘甲状腺原氨酸（TT3）和总甲状腺素（TT4）水平。采用线性混合模型和多变量线性回归模型来检验孕期四环素类抗生素暴露与母体甲状腺激素参数之间的关联。
三个孕期中四种单一四环素类抗生素及所有抗生素（四种单一四环素类抗生素之和）的检出率为5.0%-52.3%，第95百分位数浓度范围为0.11至4.84 ng/mL。在调整潜在混杂因素后，重复测量分析表明，整个孕期接触强力霉素和所有抗生素的孕妇与血清FT4和TT4水平呈负相关，但与血清TSH和TT3水平呈正相关。按孕期分层分析发现，孕早期接触强力霉素和所有抗生素与血清FT4和TT4水平呈负相关，而强力霉素与TSH水平呈正相关。在孕晚期，仅发现所有抗生素与TSH水平之间存在显著关联。
我们的结果表明，孕妇接触四环素类抗生素与母体甲状腺激素参数有关，孕早期可能是最关键的时期。需要更多研究来证实我们的发现并确定潜在的生物学机制。
