Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
Environ Res. 2021 Oct;201:111539. doi: 10.1016/j.envres.2021.111539. Epub 2021 Jun 24.
Organophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests both in agriculture and in residences, and to reduce the transmission of insect-borne diseases. Several studies have reported inverse associations between exposure to organophosphates (as a larger class) and birth outcomes but these associations have not been conclusive for pyrethroids or 2,4-D, specifically. We aimed to investigate the association between birth outcomes and urinary biomarkers of pyrethroids, organophosphates and 2,4-D among healthy pregnant women living in New York City.
We quantified urinary biomarkers of 2,4-D and of organophosphate and pyrethroid insecticides from 269 women from two cohorts: a) Thyroid Disruption And Infant Development (TDID) and b) Sibling/Hermanos cohort (S/H). We used weighted quantile sum regression and multivariable linear regression models to evaluate the associations between a mixture of urinary creatinine-adjusted biomarker concentrations and birth outcomes of length, birthweight and head circumference, controlling for covariates. We also used linear regression models and further classified biomarkers concentrations into three categories (i: non-detectable; ii: between the limit of detection and median; and iii: above the median) to investigate single pesticides' association with these birth outcomes. Covariates considered were delivery mode, ethnicity, marital status, education, income, employment status, gestational age, maternal age and pre-pregnancy BMI. Analyses were conducted separately for each cohort and stratified by child sex within each cohort.
In TDID cohort, we found a significant inverse association between weighted quantile sum of mixture of pesticides and head circumference among boys. We found that the urinary biomarkers of organophosphate chlorpyrifos, TCPy, and 2,4-D had the largest contribution to the overall mixture effect in the TDID cohort among boys (b = -0.57, 95%CI: -0.92, -0.22) (weights = 0.81 and 0.16 respectively) but not among girls. In the multivariable linear regression models, we found that among boys, for each log unit increase in 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of organophosphate chlorpyrifos) in maternal urine, there was a -0.56 cm decrease in head circumference (95%CI: -0.92, -0.19). Among boys in the TDID cohort, 2,4-D was associated with smaller head circumference in the second (b = -1.57; 95%CI: -2.74, -0.39) and third (b = -1.74, 95%CI: -2.98, -0.49) concentration categories compared to the first. No associations between pyrethroid and organophosphate biomarkers and birth outcomes were observed in girls analyzed in WQS regression or individually in linear regression models in TDID cohort. In the S/H cohort, head circumference increased with higher concentrations of 3-phenoxybenzoic acid (3-PBA, a biomarker of several pyrethroids) (b = 0.53, 95%CI: 0.03, 1.04) among boys and head circumference was lower among girls in the high compared to low category of 2,4-D (b = -2.27, 95%CI: - 3.98, -0.56). Birth length was also positively associated with the highest concentration of 2,4-D compared to the lowest among boys (b = 4.01, 95%CI: 0.02,8.00).
Weighted quantile sum of pesticides was negatively associated with head circumference among boys in one cohort. Nonetheless, due to directional homogeneity assumption in WQS no positive associations were detected. In linear regression models with individual pesticides, concentrations of TCPy were inversely associated with head circumference in boys and higher concentrations of 2,4-D was inversely associated with head circumference among girls; 2,4-D concentrations were also associated with higher birth length among boys. Concentrations of 3-PBA was positively associated with head circumference among boys.
有机磷杀虫剂和除草剂 2,4-二氯苯氧乙酸（2,4-D）被用于保护作物或控制杂草。拟除虫菊酯被用于农业和住宅中防治害虫，并减少虫媒疾病的传播。一些研究报告称，接触有机磷（作为一个更大的类别）与出生结局之间存在反比关系，但这些关联对于拟除虫菊酯或 2,4-D 具体来说，并没有得出明确的结论。我们旨在研究纽约市健康孕妇的出生结局与尿中拟除虫菊酯、有机磷和 2,4-D 的生物标志物之间的关联。
我们从两个队列（a）甲状腺干扰和婴儿发育（TDID）和（b）兄弟姐妹/ Hermanos 队列（S/H）中 269 名女性中量化了 2,4-D 和有机磷和拟除虫菊酯杀虫剂的尿生物标志物。我们使用加权分位数总和回归和多变量线性回归模型来评估生物标志物浓度与长度、出生体重和头围等出生结局之间的关联，同时控制了协变量。我们还使用线性回归模型，并进一步将生物标志物浓度分为三个类别（i：不可检测；ii：在检测限和中位数之间；iii：高于中位数）来研究单一农药与这些出生结局的关系。考虑的协变量包括分娩方式、种族、婚姻状况、教育程度、收入、就业状况、胎龄、母亲年龄和孕前 BMI。分析分别在每个队列中进行，并按每个队列中男孩和女孩的性别进行分层。
在 TDID 队列中，我们发现混合农药的加权分位数总和与男孩的头围之间存在显著的反比关系。我们发现，有机磷杀虫剂毒死蜱、TCPy 和 2,4-D 的尿生物标志物在 TDID 队列中的男孩中对整体混合物效应的贡献最大（b=-0.57，95%CI：-0.92，-0.22）（权重分别为 0.81 和 0.16），但在女孩中则没有。在多变量线性回归模型中，我们发现，对于男孩，母体尿液中 3,5,6-三氯-2-吡啶醇（TCPy，有机磷杀虫剂毒死蜱的代谢物）每增加一个对数单位，头围就会减少 0.56 厘米（95%CI：-0.92，-0.19）。在 TDID 队列中的男孩中，与第一个浓度类别相比，2,4-D 与第二个（b=-1.57；95%CI：-2.74，-0.39）和第三个（b=-1.74，95%CI：-2.98，-0.49）浓度类别与较小的头围相关。在 WQS 回归或 TDID 队列中的线性回归模型中，我们没有观察到拟除虫菊酯和有机磷生物标志物与女孩出生结局之间的关联。在 S/H 队列中，与男孩的低浓度类别相比，男孩的 3-苯氧基苯甲酸（3-PBA，几种拟除虫菊酯的生物标志物）浓度较高时，头围增加（b=0.53，95%CI：0.03，1.04），而女孩的头围在高浓度的 2,4-D 类别中较低（b=-2.27，95%CI：-3.98，-0.56）。出生长度也与男孩最高浓度的 2,4-D 相比呈正相关（b=4.01，95%CI：0.02，8.00）。
在一个队列中，农药的加权分位数总和与男孩的头围呈负相关。然而，由于 WQS 中的方向同质性假设，没有检测到阳性关联。在具有个体农药的线性回归模型中，TCPy 的浓度与男孩的头围呈反比关系，而 2,4-D 的浓度与女孩的头围呈反比关系；2,4-D 浓度也与男孩的出生长度呈正相关。3-PBA 的浓度与男孩的头围呈正相关。
