挪威母亲、父亲和儿童队列研究（MoBa）中产前有机磷农药暴露与学龄前儿童执行功能的关系。
Prenatal organophosphorus pesticide exposure and executive function in preschool-aged children in the Norwegian Mother, Father and Child Cohort Study (MoBa).
机构信息
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
出版信息
Environ Res. 2022 Sep;212(Pt D):113555. doi: 10.1016/j.envres.2022.113555. Epub 2022 May 22.
INTRODUCTION
Prenatal exposure to organophosphorus pesticides (OPPs) has been associated with neurodevelopmental deficits in children, however evidence linking OPPs with specific cognitive mechanisms, such as executive function (EF), is limited.
OBJECTIVE
This study aims to evaluate the association between prenatal exposure to OPPs with multiple measures of EF in preschool-aged children, while considering the role of variant alleles in OPP metabolism genes.
METHODS
We included 262 children with preschool attention-deficit/hyperactivity disorder (ADHD), and 78 typically developing children, from the Preschool ADHD substudy of the Norwegian, Mother, Father, and Child Cohort Study. Participants who gave birth between 2004 and 2008 were invited to participate in an on-site clinical assessment when the child was approximately 3.5 years; measurements of EF included parent and teacher rating on Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), and three performance-based assessments. We measured OPP metabolites in maternal urines collected at ∼17 weeks' gestation to calculate total dimethyl- (ΣDMP) and diethyl phosphate (ΣDEP) metabolite concentrations. We estimated multivariable adjusted β's and 95% confidence intervals (CIs) corresponding to a change in z-score per unit increase in log-ΣDMP/DEP. We further characterized gene-OPP interactions for maternal variants in PON1 (Q192R, M55L), CYP1A2 (1548T > C), CYP1A1 (IntG > A) and CYP2A6 (-47A > C).
RESULTS
Prenatal OPP metabolite concentrations were associated with worse parent and teacher ratings of emotional control, inhibition, and working memory. A one log-∑DMP increase was associated with poorer teacher ratings of EF on the BRIEF-P (e.g. emotional control domain: β = 0.55, 95% CI: 0.35, 0.74), when weighted to account for sampling procedures. We found less consistent associations with performance-based EF assessments. We found some evidence of modification for PON1 Q192R and CYP2A6 -47A > C. Association with other variants were inconsistent.
CONCLUSIONS
Biomarkers of prenatal OPP exposure were associated with more adverse teacher and parent ratings of EF in preschool-aged children.
介绍
产前接触有机磷农药（OPPs）与儿童神经发育缺陷有关，但将 OPPs 与特定认知机制（如执行功能[EF]）联系起来的证据有限。
目的
本研究旨在评估产前接触 OPPs 与学龄前儿童多种 EF 测量值之间的关联，同时考虑 OPP 代谢基因中变异等位基因的作用。
方法
我们纳入了来自挪威母婴儿童队列研究的学龄前注意缺陷多动障碍（ADHD）亚研究中的 262 名儿童和 78 名正常发育儿童。2004 年至 2008 年期间分娩的参与者在孩子大约 3.5 岁时被邀请参加现场临床评估；EF 的测量包括家长和老师对行为评定量表的评估执行功能-学龄前（BRIEF-P），以及三项基于表现的评估。我们测量了母亲在妊娠约 17 周时收集的尿液中的 OPP 代谢物，以计算总二甲基（ΣDMP）和二乙基磷酸盐（ΣDEP）代谢物浓度。我们估计了与单位对数ΣDMP/DEP 增加相对应的多变量调整β值和 95%置信区间（CI）。我们进一步表征了母体 PON1（Q192R、M55L）、CYP1A2（1548T > C）、CYP1A1（IntG > A）和 CYP2A6（-47A > C）变异体的基因-OPP 相互作用。
结果
产前 OPP 代谢物浓度与父母和老师对情绪控制、抑制和工作记忆的评分较差有关。与教师对 BRIEF-P 的 EF 评分较差相关（例如，情绪控制领域：β=0.55，95%CI：0.35，0.74），当加权考虑采样程序时，∑DMP 增加一个对数。我们发现与基于表现的 EF 评估的关联不太一致。我们发现 PON1 Q192R 和 CYP2A6 -47A > C 存在一些修饰的证据。与其他变体的关联不一致。
结论
产前 OPP 暴露的生物标志物与学龄前儿童更不利的教师和家长对 EF 的评分有关。
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