Phthalates and Phthalate Alternatives and Early Human Cardiometabolic Development

/ABSTRACT Phthalates are ubiquitous environmental endocrine-disrupting chemicals with a wide range of potential adverse health effects. Laboratory studies have identified developmental effects of phthalates on cardiovascular and adipose formation and growth, contributing to adverse cardiometabolic outcomes across the lifecourse. Human studies have only recently been able to noninvasively assess fetal cardiovascular and adipose development, and few studies have prospectively evaluated cardiometabolic outcomes following prenatal phthalate exposure. In the HPP-3D Study, 90% of pregnancies were exposed to phthalates and new chemicals used to replace phthalates (alternatives), highlighting the critical need for human studies to better understand the impact of these chemicals on cardiometabolic health. The overarching objective of this proposal is to investigate associations between prenatal phthalates and phthalate alternatives and fetal (Aims 1 and 2) and pediatric (Aim 3) cardiometabolic outcomes in the HPP-3D Study. With up to eight exposure assessment timepoints, this study has one of the most comprehensive characterizations of prenatal nonpersistent environmental chemical exposures to date. Utilizing innovative tools to repeatedly assess fetal cardiovascular outcomes and body composition, I will provide novel insight into associations between these well-characterized exposures and longitudinal fetal cardiometabolic development in the K99 phase. Building on this rich resource, I will employ a two-pronged approach to conduct follow-up of HPP-3D Study children in the R00 phase using electronic medial records (Aim 3a) and advanced cardiometabolic assessments during an in-person clinic visit on a subset of 40 children (Aim 3b). The proposal will incorporate innovative environmental mixture methods and will examine periods of susceptibility across pregnancy to appropriately quantify the human exposure experience, identify biological mechanisms, and improve targeting of future exposure investigations and interventions. With the majority of American youth having at least one cardiometabolic abnormality, there is a critical need to identify intervenable risk factors for adverse cardiometabolic development. This research will therefore provide crucial insights into the effect of endocrine-disrupting phthalates and phthalate alternatives on human cardiometabolic development, which will have implications for the etiology and prevention of cardiometabolic dysfunction. To be successful in the proposed work and launch my independent research career, I will build on my strong prior epidemiologic training with experiential and didactic professional development trainings in environmental and cardiovascular assessments and the conduct of clinical research. This training will take place within the interdisciplinary environment of the Intramural Research Program at the National Institute of Environmental Health Sciences with the support and mentoring of highly accomplished epidemiologists and physician-scientists. This career development award will launch my independent research career investigating the impact of environmental exposures on early cardiometabolic health. Project Number: 4R00ES035107-02 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Danielle Stevens | Institution: UNIV OF NORTH CAROLINA CHAPEL HILL, CHAPEL HILL, NC | Award Amount: $249,000 | Activity Code: R00 | Study Section: NSS View on NIH RePORTER: https://reporter.nih.gov/project-details/11398007