School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; MOE Key Laboratory of Population Health Across Life Cycle, No. 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, 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; MOE Key Laboratory of Population Health Across Life Cycle, 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.
Environ Int. 2020 Dec;145:106164. doi: 10.1016/j.envint.2020.106164. Epub 2020 Oct 6.
Multiple antibiotics are widely used in clinic practice and livestock husbandry, but exposure data based on repeated measurements are scarce among pregnant women. Here, we biomonitored 41 antibiotics and their two metabolites in urine samples from 3235 pregnant women over three trimesters. Spearman's correlation coefficient, intraclass correlation coefficient (ICC), percentile analysis and linear mixed models were employed to evaluate the correlations, variability, co-exposure patterns and predictors of antibiotics, respectively. Pregnant urinary creatinine-adjusted concentrations of antibiotics were used to estimate daily exposure dose and assessed health risks. The target antibiotics were detected in more than 90% of urine samples, primarily as preferred as veterinary antibiotics (PVAs), and the 95th percentile urinary concentrations of each individual antibiotics were range from below the limits of detection to 5.74 ng/mL. We observed considerable within-subject variation (ICC: 0.05-0.63) of urinary antibiotics concentrations during pregnancy. More than half pregnant women were co-exposed to two or more antibiotics of different usage classes, while both co-exposure to high percentiles of three usage antibiotics at one trimester or exposure to single usage antibiotics at high-dose through three trimesters were infrequent in the study population, and most pregnant women were continuously exposed to low-dose PVAs across pregnancy. A total of 4.5% samples were showed hazard index values exceeding 1 during entire pregnancy. Urinary levels of antibiotics associated with residence, maternal age and education, pre-pregnancy BMI, household income and gestational week, especially vary by sampling seasons. Taken together, most pregnant women were frequently exposure to low-dose PVAs across pregnancy and some were in a health risk associated with the disturbance of gut microbiota. Multiple measurements of urinary antibiotic concentrations are essential to more accurate charactering the exposure levels during pregnancy. Several predictors of urinary antibiotics should be taken into consideration in future researches.
多种抗生素广泛应用于临床实践和畜牧业，但孕妇的暴露数据基于重复测量仍十分有限。在此，我们对 3235 名孕妇在三个孕期的尿液样本中进行了 41 种抗生素及其两种代谢物的生物监测。分别采用 Spearman 相关系数、组内相关系数（ICC）、百分位数分析和线性混合模型来评估相关性、变异性、共暴露模式和抗生素的预测因子。使用孕妇尿液肌酐校正后的抗生素浓度来估计每日暴露剂量并评估健康风险。目标抗生素在超过 90%的尿液样本中被检测到，主要为兽用抗生素（PVAs），每种抗生素个体的第 95 百分位尿液浓度范围为检测限以下至 5.74ng/mL。我们观察到孕妇怀孕期间尿液抗生素浓度存在相当大的个体内变异性（ICC：0.05-0.63）。超过一半的孕妇同时暴露于两种或更多不同用途类别的抗生素，而在一个孕期内同时暴露于三种用途抗生素的高百分位数或在三个孕期内暴露于高剂量的单一用途抗生素的情况并不常见，且大多数孕妇在整个孕期内持续接触低剂量的 PVAs。在整个孕期中，共有 4.5%的样本显示危害指数值超过 1。与居住地、母亲年龄和教育程度、孕前 BMI、家庭收入和孕周相关的抗生素尿液水平存在差异，尤其与采样季节有关。总之，大多数孕妇在整个孕期中频繁接触低剂量的 PVAs，而一些孕妇则存在与肠道微生物群紊乱相关的健康风险。抗生素尿液浓度的多次测量对于更准确地描述孕期暴露水平至关重要。未来的研究应考虑到抗生素尿液的多个预测因子。
