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

• 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
• 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

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）：越来越多的证据表明，在子宫内暴露于有毒物质可能对儿童神经发育产生长期影响。最近的一些研究表明，母亲产前尿邻苯二甲酸酯，BPA和有机磷生物标志物与儿童的认知和行为异常有关。虽然这些研究在建立这些关系的可解释性方面是基础性的，但没有一项研究能够评估临床证实的行为表型，因为注意力缺陷多动障碍 注意力缺陷多动障碍（ADHD）相对罕见，以前的研究使用了相对较小的出生队列。到 为了解决文献中的这一空白，我们提出了一项在挪威母亲和儿童队列（MoBa）中进行的巢式病例队列研究，该队列是一个由超过100，000名孕妇组成的纵向出生队列，旨在调查邻苯二甲酸酯，BPA和有机磷农药生物标志物暴露与学龄前ADHD之间的关系。将选择所有临床确诊的ADHD病例（n = 265），并将收集队列的随机样本（n = 530）作为对照组。通过使用巢式病例队列设计，我们既可以有效地估计ADHD的相对危险度，也可以连续检查暴露与症状严重程度之间的关系。邻苯二甲酸酯和BPA暴露与神经行为结果之间的一个合理途径是母体甲状腺激素紊乱。因此，我们也将研究这些暴露的生物标志物和母体甲状腺激素功能之间的关系。此外，修饰的有机磷-ADHD的关系的功能基因变异的关键代谢酶，PON 1，将进行检查。最后，我们将采用先进的贝叶斯模型来处理多个相关的风险敞口。 公共卫生相关性：孕妇被动地暴露于他们使用的产品和他们吃的食物中的无数环境化学物质。其中一些暴露已被发现穿过胎盘;然而，即使没有直接的胎儿暴露，后代神经发育障碍可能是由妊娠期间母体甲状腺激素系统相对较小的干扰介导的。有一个新兴的文献链接到某些毒物暴露梯度的行为症状，然而，到目前为止，只有薄弱的证据将这些风险与临床确认的行为表型。本研究将通过阐明选择性毒物暴露与定义明确的行为终点ADHD之间的关系来解决文献中的这一关键空白。