Department of Maternal, Child and Adolescent Health, 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, No 81 Meishan Road, Hefei 230032, Anhui, China.
Department of Maternal, Child and Adolescent Health, 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, No 81 Meishan Road, Hefei 230032, Anhui, China.
Environ Int. 2020 Dec;145:106114. doi: 10.1016/j.envint.2020.106114. Epub 2020 Oct 6.
The potential maternal and neonatal thyrotoxicity associated with exposure to arsenic during pregnancy is very limited and unclear.
This study aimed to examine the associations between arsenic exposure levels in maternal and cord serum and maternal and neonatal thyroid hormone parameters in a prospective birth cohort study.
The study including 2089 mother-neonate pairs was based upon Ma'an Shan birth cohort study in China. The exposure variables including maternal serum arsenic levels in the first, second and third trimester and average arsenic exposure level during pregnancy and cord serum arsenic level. Maternal serum TSH and FT4 levels in the first, second and third trimester and cord serum TSH and FT4 levels were determined using the electrochemiluminescence immunoassay with Cobas Elecsys 411. Linear mixed models were used to examine associations between arsenic exposure variables during pregnancy and maternal thyroid hormone parameters, and multiple linear regression analyses were used to examine associations between arsenic exposure during pregnancy and neonatal thyroid hormone parameters. Bayesian kernal machine regression (BKMR) analyses based on a kernel function were also used to examine the effects of exposure to metal mixtures (arsenic, mercury, cadmium and selenium).
The geometric means of arsenic exposure levels across 3 trimesters were 1.74 μg/L, 1.81 μg/L and 1.99 μg/L, respectively, and 1.90 μg/L in cord serum; the geometric means of maternal FT4 levels across 3 trimesters were 16.91 pmol/L, 11.91 pmol/L and 13.16 pmol/L, respectively, and 16.10 pmol/L in cord serum; the geometric means of maternal TSH levels across 3 trimesters were 1.27 μIU/mL, 2.32 μIU/mL and 2.08 μIU/mL, respectively, and 8.47 μIU/mL in cord serum. Maternal serum arsenic levels in the first, seond, third trimester and average arsenic exposure level during pregnancy were all not associated with maternal thyroid hormone parameters after adjustment for all the covariates, the adjusted β (95% CI) were -0.002 (-0.10 to 0.09), 0.05 (-0.05 to 0.16), -0.09 (-0.17 to 0.003) and -0.05 (-0.22 to 0.11) for maternal FT4, respectively; and -0.005 (-0.04 to 0.03), -0.003 (-0.04 to 0.03), -0.004 (-0.03 to 0.02) and -0.01 (-0.06 to 0.04) for maternal lnTSH, respectively. Maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy were all inversely associated with neonatal FT4 level after adjustment for all the confounders, the adjusted β (95% CI) were -0.19 (-0.31 to -0.07), -0.14 (-0.26 to -0.01), -0.22 (-0.42 to -0.02), respectively; and cord serum arsenic level was positively related with neonatal TSH level, the adjusted β (95% CI) were 0.04 (0.001 to 0.08). The adverse joint toxic effect of the four metals in maternal serum in the first trimester and in cord serum on neonatal thyroid hormone parameters were also found.
In this study, exposure to low levels of arsenic during pregnancy could directly affect neonatal thyroid hormone parameters without being mediated by maternal effect of exposure, and maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy and cord serum arsenic level may be risk factors affecting neonatal thyroid hormones. These findings indicate that neonates are more sensitive to the thyrotoxicity of arsenic exposure even at low levels. In addition, the adverse joint toxic effect of metal mixtures is also worthy of attention.
怀孕期间接触砷与潜在的母婴甲状腺毒性相关，但其影响非常有限且不明确。
本研究旨在探讨前瞻性出生队列研究中母体和脐带血清中的砷暴露水平与母体和新生儿甲状腺激素参数之间的关系。
该研究包括 2089 对母婴对，基于中国马鞍山市出生队列研究。暴露变量包括母亲在妊娠第一、二、三期和妊娠期间平均砷暴露水平以及脐带血清砷水平。使用电化学发光免疫分析法，使用 Cobas Elecsys 411 测定母体在妊娠第一、二、三期和脐带血清 TSH 和 FT4 水平。线性混合模型用于检查妊娠期间砷暴露变量与母体甲状腺激素参数之间的关系，多元线性回归分析用于检查妊娠期间砷暴露与新生儿甲状腺激素参数之间的关系。还使用基于核函数的贝叶斯核机回归（BKMR）分析来检查金属混合物（砷、汞、镉和硒）暴露的影响。
妊娠前三个季度的砷暴露水平几何平均值分别为 1.74μg/L、1.81μg/L 和 1.99μg/L，脐带血清中为 1.90μg/L；妊娠前三个季度母体 FT4 水平几何平均值分别为 16.91pmol/L、11.91pmol/L 和 13.16pmol/L，脐带血清中为 16.10pmol/L；妊娠前三个季度母体 TSH 水平几何平均值分别为 1.27μIU/mL、2.32μIU/mL 和 2.08μIU/mL，脐带血清中为 8.47μIU/mL。调整所有协变量后，母亲妊娠第一、二、三期血清砷水平和妊娠期间平均砷暴露水平均与母体甲状腺激素参数无关，调整后的β（95%CI）分别为-0.002（-0.10 至 0.09）、0.05（-0.05 至 0.16）、-0.09（-0.17 至 0.003）和-0.05（-0.22 至 0.11）对于母体 FT4；以及-0.005（-0.04 至 0.03）、-0.003（-0.04 至 0.03）、-0.004（-0.03 至 0.02）和-0.01（-0.06 至 0.04）对于母体 lnTSH。调整所有混杂因素后，母亲妊娠第一、二季度血清砷水平和妊娠期间平均砷暴露水平均与新生儿 FT4 水平呈负相关，调整后的β（95%CI）分别为-0.19（-0.31 至-0.07）、-0.14（-0.26 至-0.01）、-0.22（-0.42 至-0.02）；脐带血清砷水平与新生儿 TSH 水平呈正相关，调整后的β（95%CI）为 0.04（0.001 至 0.08）。还发现母体血清中前三个月和脐带血清中四种金属的联合毒性作用对新生儿甲状腺激素参数有不利影响。
在这项研究中，妊娠期间接触低水平的砷可能直接影响新生儿的甲状腺激素参数，而不受母体暴露的影响，妊娠第一、二、三期和妊娠期间的母体血清砷水平以及脐带血清砷水平可能是影响新生儿甲状腺激素的危险因素。这些发现表明，即使在低水平下，新生儿对砷暴露的甲状腺毒性也更为敏感。此外，金属混合物的联合毒性作用也值得关注。
