Childhood obesity, cardiometabolic abnormalities, and neurodevelopmental disorders are prevalent, impact the health and well-being of children and their families, and have substantial financial costs. Research demonstrates that early life environmental exposures increase the risk of these disorders. While there has been justifiable emphasis on studying environmental exposures during gestation and early childhood, there is limited epidemiologic data on the impact of maternal preconception exposures on children?s health and even less research on the effect of paternal preconception exposures. Experimental studies in animals provide compelling data showing that maternal and paternal preconception exposures to stress and altered diet affect offspring phenotypes through heritable epigenetic modifications encoded in gametes. Despite support for the scientific premise that preconception environmental exposures have the potential to affect children?s health, there is an almost complete lack of human studies. Endocrine disrupting chemicals are of particular concern because they disrupt hormonal signaling and alter epigenetic programming of gametes and embryos, which in turn may adversely affect child health. One class of chemicals of high concern is phthalates, multifunctional chemicals used in many consumer products and for which there is ubiquitous general population exposure. Our multidisciplinary team of investigators proposes a new study of children who were born to couples who participated in our ongoing prospective preconception cohort study. We previously analyzed multiple urine samples for phthalate metabolites from mothers and fathers before conception and from women during pregnancy. In this proposal, we will conduct in-person visits on 381 eligible children (7-10 years of age) and collect detailed measures of child neurobehavior, anthropometry, and cardiometabolic function. We have collected or will collect extensive maternal, paternal, and child-level covariate data, including diet, SES, medical history, caregiving environment, and physical/sedentary activity.
Our specific aims are to determine the extent to which maternal and paternal preconception phthalate exposures are individually and/or jointly associated with: 1) increased behavior problems, poorer executive function, and reduced cognitive abilities, 2) increased adiposity and reduced satiety, 3) impaired glucose and insulin homeostasis, increased blood pressure, and altered serum lipids. Our innovative proposed study represents a unique opportunity to determine if maternal and paternal pre-conception phthalate exposure affects children?s health, while also controlling for prenatal and childhood phthalate exposure. Other innovations include the availability of multiple maternal and paternal preconception urine samples to assess phthalate exposure, state of the art assessment of child health outcomes, and use of novel statistical approaches to study phthalate mixtures and windows of vulnerability. Our proposed study will provide critical data on the effect of maternal and paternal preconception phthalate exposure on child health, and thus identify modifiable risk factors for prevalent childhood diseases.

Public Health Relevance

The preconception period represents a unique and unstudied period of vulnerability to environmental chemical exposures. This project will determine if maternal and paternal preconception phthalate exposures are associated with child neurodevelopment, obesity, and cardiometabolic function in a prospective cohort of mother-father-child triads. These results will help determine if maternal and paternal preconception environmental chemical exposures play a role in children?s health and well-being.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
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Gray, Kimberly A
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Harvard University
Public Health & Prev Medicine
Schools of Public Health
United States
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Braun, Joseph M (2018) Pre-conception susceptibility to endocrine disruptors. Nat Rev Endocrinol 14:505-506