Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Environ Int. 2019 Nov;132:105124. doi: 10.1016/j.envint.2019.105124. Epub 2019 Aug 31.
Animal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone.
To investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations.
This study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N = 715) or cord blood (N = 482) thyroid hormone measurements were included. OP pesticides exposure was assessed at <18, 18-25, and >25 weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used.
There was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure.
Gestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood thyroid hormone concentrations. These findings do not support a mediating role for serum thyroid hormone availability in the relation of early life exposure to low levels of OP pesticides with child neurodevelopment. However, disruption of the thyroid system at tissue level cannot be excluded. In addition, this is one of the first studies on this subject and measurement error in DAP metabolites might have resulted in imprecise estimates. Future studies should use more urine samples to increase precision and should investigate specific OP pesticide metabolites.
动物研究表明，有机磷（OP）农药暴露会影响甲状腺功能，但人类的证据仍然很少且不一致。妊娠期暴露尤其值得关注，因为甲状腺激素对胎儿大脑发育至关重要。OP 农药能够穿过胎盘和血脑屏障，并可能干扰受甲状腺激素调节的胎儿发育过程。
研究妊娠期 OP 农药暴露与产妇和脐带血甲状腺激素浓度之间的关系。
本研究嵌入 Generation R（荷兰鹿特丹），这是一项前瞻性的基于人群的出生队列研究。纳入了进行 OP 农药评估且有产妇（N=715）或脐带血（N=482）甲状腺激素测量值的母婴对。在<18、18-25 和>25 孕周时，通过测量 6 种尿二烷基磷酸（DAP）代谢物来评估 OP 农药暴露情况。在产妇和脐带血中测量促甲状腺激素（TSH）和游离甲状腺素（FT4）。产妇测量值还包括总甲状腺素（TT4）和甲状腺过氧化物酶抗体（TPOAb）。为了研究肌酐校正的 DAP 代谢物浓度与甲状腺功能和 TPOAb 的关系，使用包含相关混杂因素的多变量线性回归模型进行分析。
DAP 代谢物与妊娠期间产妇 TSH、FT4、TT4 或 TPOAb 浓度均无关联。同样，DAP 代谢物与脐带血 TSH 或 FT4 也无关联。当在各个时间点分析 DAP 浓度或作为平均妊娠暴露时，结果并未改变。
在城市人群中，通过反复测量尿 DAP 代谢物浓度评估的妊娠期 OP 农药暴露与产妇或脐带血甲状腺激素浓度无关。这些发现不支持血清甲状腺激素供应在早期生活中接触低水平 OP 农药与儿童神经发育之间的关系中起中介作用。但是，不能排除甲状腺系统在组织水平受到干扰的可能性。此外，这是该主题的首批研究之一，DAP 代谢物的测量误差可能导致估计不准确。未来的研究应使用更多的尿液样本以提高精度，并应研究特定的 OP 农药代谢物。
