A big data approach to phthalates, hormones, and ADHD

针对邻苯二甲酸盐、激素和多动症的大数据方法

• 批准号: 9788457
• 负责人: Marc G Weisskopf
• 金额: $ 18.52万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788457
• 关键词: Adult; Age; Androgens; Attention deficit hyperactivity disorder; Big Data; Chemicals; Child; Childhood; Clinical; Comorbidity; Computerized Medical Record; Cryptorchidism; Data; Database Management Systems; Development; Diagnosis; Disease; Electronic Health Record; Endocrine; Endocrine Disruptors; Endocrine disruption; Environment; Excipients; Exposure to; First Pregnancy Trimester; Genes; Goals; Health; Health system; Heritability; High Prevalence; High Risk Woman; Hormonal; Hormones; Hypospadias; ICD-9; Individual; Intervention; Israel; Lead; Maternal Exposure; Mediating; Medical; Mental disorders; Mothers; Natural experiment; Occupational Exposure; Occupations; Parents; Pharmaceutical Preparations; Pharmacologic Substance; Play; Pregnancy; Pregnant Women; Property; Public Health; Quality of life; Reporting; Research; Risk; Risk Factors; Role; Signal Pathway; Signal Transduction; Substance abuse problem; System; Thyroid Gland; Thyroid Hormones; Underachievement; Woman; Work; aged; androgenic; boys; cost; design; fetal; hazard; high risk; in utero; male; modifiable risk; personal care products; phthalates; pill; prenatal exposure; public health intervention; reproductive tract; toxicant

Project Summary/Abstract Several lines of evidence suggest that alterations in the fetal hormonal environment may play a critical role in the development of attention deficit/hyperactivity disorder (ADHD), and it has been suggested that maternal exposure to phthalates—a class of endocrine disrupting chemicals (EDCs)—may lead to ADHD, although direct evidence for this is limited. Our goal is to examine the association between in utero endocrine disruption and risk of ADHD in the child. Specifically, we will examine maternal exposure to phthalates during pregnancy, maternal 1st trimester thyroid hormone levels, and male reproductive tract disorders in the child (which are indicative of in utero hypoandrogenicity). To do this we will take advantage of longitudinal electronic medical record data from a large Health System in Israel. The Israeli Maccabi Health System database contains the health and pharmaceutical data of over 2 million people. We have validated ICD-9 identified ADHD diagnoses in the Maccabi Health System data, in which there are approximately 64,000 ADHD cases. We have recently found that certain brands of medications contain extremely high levels of phthalates as excipients in the pill coating and can identify mothers who use phthalate containing medication during pregnancy in the Maccabi data in order to identify a highly exposed group of mothers. This offers a unique opportunity to explore the results of what is effectively a natural experiment of phthalate exposure: by also identifying mothers with the same underlying conditions, but those who use different brands of the same medication, but ones that do not have phthalates as excipients, we can determine whether any association is confounded by indication. Pregnant mothers in Maccabi are also screened for thyroid conditions, data that we can use to examine the role of maternal thyroid status during pregnancy and ADHD as well as whether these thyroid conditions account for any identified association with phthalates. We can also examine whether boys with male reproductive tract disorders—indicative of a hypoandrogenic in utero environment—are at higher risk of ADHD.

项目摘要/摘要 几条证据表明，胎儿荷尔蒙环境的改变可能会起到关键作用 在注意力不足/多动症（ADHD）的发展中的作用，已经提出 孕产妇接触邻苯二甲酸盐（一类内分泌破坏化学物质（EDC））可能导致多动症， 尽管直接证据是有限的。我们的目标是检查子宫内分泌中的关联 儿童多动症的破坏和风险。具体而言，我们将检查在邻苯二甲酸盐的材料 怀孕，母亲的第一例甲状腺激素水平和儿童的雄性生殖障碍 （在子宫内发育不良中指示）。为此，我们将利用纵向电子 来自以色列大型卫生系统的病历数据。以色列马卡比卫生系统数据库 包含超过200万人的健康和药物数据。我们已经验证了ICD-9已确定 Maccabi卫生系统数据中的ADHD诊断，其中大约有64,000例ADHD病例。 最近，我们发现某些品牌的药物含有极高的邻苯二甲酸盐 药丸涂料中的赋形剂，可以识别在邻苯二甲酸酯中使用含有药物的母亲 马卡比数据中的怀孕是为了确定一群高度暴露的母亲。这提供了独特的 探索有效自然暴露实验结果的机会： 确定母亲具有相同的潜在条件，但是那些使用不同品牌的母亲 药物，但是没有邻苯二甲酸盐作为赋形剂的药物，我们可以确定任何关联是 被指示混淆。马卡比的怀孕母亲也被筛选为甲状腺条件，我们的数据 可以用来检查怀孕期间和多动症期间母体甲状腺状况的作用 甲状腺条件解释了与邻苯二甲酸盐的任何确定关联。我们还可以检查男孩是否 与男性生殖道疾病（指属性不足环境中的疾病）处于较高的风险 多动症。