Prenatal exposure to organophosphate esters and behavioral development in young children in the Pregnancy, Infection, and Nutrition Study
Prenatal exposure to organophosphate esters and behavioral development in young children in the Pregnancy, Infection, and Nutrition Study
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DOI：
10.1016/j.neuro.2019.03.007
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发表时间：
2019-07-01
期刊：
影响因子：
3.4
通讯作者：
Daniels, Julie L.
中科院分区：
文献类型：
--
作者：
Doherty, Brett T.;Hoffman, Kate;Daniels, Julie L.
有机磷酸酯（OPEs）通常用作消费品中的增塑剂和阻燃剂，在大多数被研究的人群中，接触有机磷酸酯的情况相对普遍。这可能令人担忧，因为一些OPEs可能具有神经毒性、内分泌干扰和干扰行为发育；然而，观测证据是有限的。我们使用来自妊娠、感染和营养研究（一项前瞻性出生队列研究）的数据，调查妊娠期间母体OPE代谢物浓度与后代行为发育之间的关系。妇女在怀孕期间提供尿液样本，分析OPE代谢物的浓度，包括二苯基磷酸（DPHP），二（1,3-二氯-2-丙基磷酸）（BDCIPP），异丙基苯基磷酸（ip-PPP）和1-羟基-2-丙基二（1-氯-2-丙基）磷酸（BCIPHIPP）。在大约36个月时，用儿童行为评估系统（第二版）（BASC-2）对后代的行为发展进行评估。使用线性回归来估计特定重力校正的OPE代谢物浓度与儿童BASC-2评分之间的关系，并对母亲年龄、母亲BMI、母亲种族、母亲教育程度、家庭收入、母亲抑郁、家庭环境质量和性别进行了调整。较高的BDCIPP浓度与较高的行为症状指数（1对3个分位：β = 3.03; 95% CI = 0.40, 5.67）和外化问题（1对3个分位：β = 2.49; 95% CI: -0.12, 5.10）综合得分相关。在BASC-2量表中，BDCIPP与退缩、注意力问题、抑郁、多动和攻击行为的相关性最强。DPHP浓度也与外化问题和行为症状指数复合材料得分较高相关，但不像BDCIPP那么强烈。相反，较高的ip-PPP浓度与较少的不良行为症状相关，包括与内化问题复合指数呈负相关（第1与第3分位数：β = -3.74; 95% CI = -6.75, -0.74）和成分量表。BCIPHIPP与任何测量的行为结果没有很强的相关性。我们的研究结果表明，母亲在怀孕期间较多地暴露于三（1,3-二氯-2-丙基磷酸）（TDCIPP， BDCIPP的母体化合物）和三苯基磷酸（TPHP， DPHP的母体化合物）与儿童的不良行为发展有关。我们的研究提供了越来越多的证据，证明产前暴露于OPE对发育的不利影响，并强调了进一步研究这种无处不在的化学物质家族的风险特征的必要性。
Organophosphate esters (OPEs) are commonly used as plasticizers and flame retardants in consumer products, and exposure is relatively ubiquitous in most populations studied. This may be of concern as some OPEs may be neurotoxic, endocrine-disrupting, and interfere with behavioral development; however, observational evidence is limited. We used data from the Pregnancy, Infection, and Nutrition Study, a prospective birth cohort study, to investigate associations between maternal OPE metabolite concentrations during pregnancy and behavioral development in offspring. Women provided a urine sample during pregnancy that was analyzed for concentrations of OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). Offspring's behavioral development was assessed by the Behavioral Assessment System for Children (2nd Edition) (BASC-2) at approximately 36 months. Linear regression was used to estimate associations between tertiles in specific gravity-corrected OPE metabolite concentrations and children's scores on the BASC-2, adjusted for maternal age, maternal BMI, maternal race, maternal education, familial income, maternal depression, quality of the home environment, and sex. Higher BDCIPP concentrations were associated with higher scores on the Behavioral Symptoms Index (1st vs. 3rd tertile: beta = 3.03; 95% CI = 0.40, 5.67) and Externalizing Problems (1st vs. 3rd tertile: beta = 2.49; 95% CI: -0.12, 5.10) composites. Among BASC-2 scales, BDCIPP was most strongly associated with Withdrawal, Attention Problems, Depression, Hyperactivity, and Aggression. DPHP concentrations were also associated with higher scores on the Externalizing Problems and Behavioral Symptoms Index composites, but not as strongly as BDCIPP. Conversely, higher concentrations of ip-PPP were associated with fewer adverse behavioral symptoms, including an inverse association with the Internalizing Problems composite (1st vs. 3rd tertile: beta = -3.74; 95% CI = -6.75, -0.74) and constituent scales. BCIPHIPP was not strongly associated with any measured behavioral outcomes. Our results suggest that greater maternal exposure to tris(1,3-dichloro-2-propyl phosphate) (TDCIPP, parent compound of BDCIPP) and, to a lesser degree, triphenyl phosphate (TPHP, parent compound of DPHP) during pregnancy is associated with adverse behavioral development in children. Our study contributes to the growing body of evidence pertaining to adverse developmental effects of prenatal OPE exposure and highlights the need for further research to characterize risks associated with this ubiquitous family of chemicals.