A Prospective Study of Per-and Polyfluoroalkyl Substance (PFAS) Mixtures and Pregnancy Outcomes in the Study of Environment, Lifestyle, and Fibroids - Per- and polyfluoroalkyl substances (PFAS) are known endocrine disrupting chemicals (EDCs), and exposure to PFAS has been associated with adverse pregnancy outcomes, including spontaneous abortion (SAB), preterm birth (PTB), and small for gestational age (SGA) births. However, less is known about 1) PFAS mixtures, 2) modifiable factors (e.g., perceived stress) and 3) underlying biological pathways of PFAS perinatal toxicity. The aims of this proposal are to investigate associations of a PFAS mixture with pregnancy outcomes (SAB, gestational age, birth size), describe the modifying role of perceived stress, and identify the biological pathways underlying PFAS perinatal toxicity using untargeted metabolomics data in the Study of Environment, Lifestyle, and Fibroids (SELF). We will leverage existing data SELF, which is an extant cohort of reproductive-aged Black women from Detroit, MI. Participants were recruited between 2010 and 2012 and were 23-35 years at enrollment. PFAS concentrations were measured in baseline plasma samples; pregnancy outcomes were prospectively assessed using structured questionnaires at follow-up visits; and all covariate data were collected in questionnaires or clinic visits at baseline and each follow-up visit. In the K99 phase of the award, Dr. Samantha Schildroth (PI) proposes the following aims: 1) evaluate the association of a PFAS mixture with pregnancy outcomes (SAB, gestational age, birth size); and 1B) in a sub-aim, examine perceived stress scores as a modifier of the PFAS mixture. The R00 phase of the award will build on the K99 phase by identifying biological pathways related to PFAS toxicity. This phase of the award will address the following aims: 2) identify metabolic pathways associated with PFAS using metabolomics data; 3A) quantify the mediating pathway(s) between the PFAS mixture and pregnancy outcomes that operate through metabolites identified in Aim 2; and 3B) in a sub-aim, examine the role of perceived stress as a modifier of the mediating pathway(s) identified in Aim 3A. The research in this proposal will address critical knowledge gaps in the literature by assessing the perinatal toxicity of PFAS mixtures, which will serve to inform public health interventions aimed at reducing adverse pregnancy outcomes. In addition, this award will provide Dr. Schildroth with foundational training in perinatal epidemiology, metabolomics, environmental toxicology, and modifiable psychosocial factors under the guidance of an expert, interdisciplinary team of researchers, allowing for her successful transition into an independent researcher focused at the nexus of chemical mixtures, metabolomics, and women’s and children’s health.
