A big data approach to phthalates, hormones, and ADHD

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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.