Prenatal Toxicant Exposure and Risk of Attention-Deficit Hyperactivity Disorder

产前有毒物暴露和注意力缺陷多动障碍的风险

基本信息

批准号：
8346378
负责人：
Stephanie Engel
金额：
$ 59.7万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-30 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8346378
关键词：
Address Age Attention deficit hyperactivity disorder Behavioral Behavioral Symptoms Biological Markers Birth Child Clinical Cognitive Cohort Studies Data Data Collection Development Dibutyl Phthalate Eating Emotional Enzymes Equation Exposure to Food Functional disorder Genes Genetic Polymorphism Genetic Variation Genotype Intelligence Link Literature Maternal Exposure Measures Mediating Mediation Memory impairment Metabolism Methodology Minor Modeling Modification Mothers Neurodevelopmental Impairment Nursery Schools Organophosphates Outcome Paraoxonase 1 Pathway interactions Performance Perinatal Exposure Pesticides Phenotype Placenta Plasma Population Predisposition Pregnancy Pregnant Women Problem behavior Psychometrics Regulation Relative Risks Reporting Research Infrastructure Risk Role Sampling Severities Short-Term Memory Symptoms System Thyroid Function Tests Thyroid Gland Thyroid Hormones Thyrotropin Thyroxine Time Toxicant exposure Urine bisphenol A boys clinical phenotype cognitive function cohort comparison group design early childhood environmental chemical externalizing behavior in utero neurobehavioral neurodevelopment offspring phthalates prenatal prenatal exposure remediation sex toxicant urinary

项目摘要

DESCRIPTION (provided by applicant): There is accumulating evidence that exposure to toxicants in utero can have long-lasting consequences on child neurodevelopment. A number of recent studies have linked maternal prenatal urinary phthalate, BPA and organophosphate biomarkers to cognitive and behavioral abnormalities in children. Although these studies have been foundational in establishing the plausibility of these relations, none have been powered to evaluate clinically-confirmed behavioral phenotypes, since attention-deficit hyperactivity disorder (ADHD) is relatively rare and the previous studies have utilized relatively small birth cohorts. To address this gap in the literature, we propose a nested case-cohort study within the Norwegian Mother and Child Cohort (MoBa), a longitudinal birth cohort consisting of over 100,000 pregnancies, in order to investigate the relation between exposure to phthalate, BPA and organophosphate pesticide biomarkers and preschool ADHD. All clinically-confirmed cases of ADHD will be selected (n = 265), and a random sample of the cohort (n = 530) will be assembled to serve as the comparison group. By using the nested case-cohort design, we can both validly estimate the relative risk of ADHD and also examine the relationship between exposure and symptom severity continuously. A plausible pathway linking phthalate and BPA exposure to neurobehavioral outcomes is maternal thyroid hormone disruption. Thus we will also be investigating the relations between these biomarkers of exposure and maternal thyroid hormone function. Additionally, modification of the organophosphate-ADHD relation by functional gene variants in a key metabolism enzyme, PON1, will be examined. Finally, we will be incorporating sophisticated Bayesian models to handle multiple correlated exposures using state-of-the-art methodology. PUBLIC HEALTH RELEVANCE: Pregnant women are passively exposed to countless environmental chemicals from the products they use and the food they eat. Some of these exposures have been found to cross the placenta; however, even without direct fetal exposure, offspring neurodevelopmental impairment could potentially be mediated by relatively minor disruptions in the maternal thyroid hormone system during pregnancy. There is an emerging literature linking certain toxicant exposures to gradients in behavioral symptoms; however, as of yet there is only weak evidence linking these exposures to a clinically-confirmed behavioral phenotype. This study will address this critical gap in the literature by elucidating the relationsip between select toxicant exposures and a well-defined behavioral endpoint, ADHD.

描述（由申请人提供）：有累积的证据表明，子宫内对毒物的暴露可能会对儿童神经发育产生长期的后果。最近的许多研究已将孕产前尿尿尿，BPA和有机磷酸盐生物标志物与儿童的认知和行为异常联系起来。尽管这些研究是建立这些关系的合理性的基础，但由于注意力缺陷多动症障碍，没有动力评估临床确认的行为表型（ADHD）相对较少，并且先前的研究使用了相对较小的出生队列。到在文献中解决了这一差距，我们提出了一项在挪威母亲和儿童队列（MOBA）中进行的嵌套病例研究研究，这是一个由超过100,000个怀孕组成的纵向出生队列，以研究暴露于邻苯二甲酸酯，BPA，BPA，BPA和有机磷酸盐的生物标志物和预设症之间的关系。将选择所有临床确认的ADHD病例（n = 265），并且将组装同类的随机样本（n = 530）作为比较组。通过使用嵌套的案例 - 霍特设计，我们既可以有效地估计多动症的相对风险，还可以连续检查暴露与症状严重程度之间的关系。孕妇甲状腺激素的破坏是将邻苯二甲酸酯和BPA暴露与神经行为结局联系起来的合理途径。因此，我们还将研究这些暴露的生物标志物与母体甲状腺激素功能之间的关系。此外，将检查通过功能基因变体对关键代谢酶PON1中功能基因变异的修饰。最后，我们将使用最先进的方法结合复杂的贝叶斯模型来处理多个相关的暴露。公共卫生相关性：孕妇从所使用的产品和所吃的食物中被动地接触到无数环境化学物质。这些暴露中的一些已被发现越过胎盘。但是，即使没有直接的胎儿暴露，怀孕期间母体甲状腺激素系统中的后代神经发育障碍也可能是通过相对较小的破坏来介导的。有新兴的文献将某些毒性暴露与行为症状的梯度联系起来。但是，到目前为止，只有较弱的证据将这些暴露与临床确认的行为表型联系起来。这项研究将通过阐明精选毒物暴露与明确定义的行为终点ADHD之间的关系来解决文献中的这一关键差距。