Associations of maternal per- and polyfluoroalkyl substance plasma concentrations during pregnancy with offspring polycystic ovary syndrome and related characteristics in project viva

Zifan Wang; Abby Fleisch; Sheryl L Rifas-Shiman; Antonia M Calafat; Tamarra James-Todd; Brent A Coull; Jorge E Chavarro; Marie-France Hivert; Rachel C Whooten; Wei Perng; Emily Oken; Shruthi Mahalingaiah

doi:10.1016/j.envres.2025.120786

Associations of maternal per- and polyfluoroalkyl substance plasma concentrations during pregnancy with offspring polycystic ovary syndrome and related characteristics in project viva

Environ Res. 2025 Jan 9:268:120786. doi: 10.1016/j.envres.2025.120786. Online ahead of print.

Authors

Affiliations

¹ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: [email protected].
² Center for Interdisciplinary Population and Health Research, MaineHealth Institute for Research, Westbrook, ME, USA; Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA.
³ Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
⁴ Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁵ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸ Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, USA.
¹⁰ Department of Epidemiology and the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹¹ Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹² Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.

PMID: 39798662
DOI: 10.1016/j.envres.2025.120786

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring.

Methods: We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002. We examined associations of maternal prenatal (median: 9.6 weeks gestation) plasma concentrations of six PFAS (log2 transformed) with PCOS and related characteristics among daughters during mid-to-late adolescence. We estimated the associations of single PFAS and PFAS as a mixture with each outcome, using logistic regression and quantile g-computation, respectively, adjusting for parity, and maternal sociodemographic and other lifestyle/health factors.

Results: Among the 322 mother-daughter pairs, the majority of mothers identified as non-Hispanic White and had a college degree, and 13% of daughters had either self-reported PCOS or probable PCOS based on irregular menstrual cycles and clinical or biochemical markers of hyperandrogenism. Among all daughters, there were 27% with irregular menstrual cycles, 34% with hirsutism, and 6% with moderate-to-severe acne. When fully adjusted for confounders, per doubling of maternal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) concentration was associated with higher odds of self-reported PCOS [OR (95% CI) = 2.66 (1.18, 5.99)], and per doubling of maternal perfluorononanoate (PFNA) concentration was associated with higher odds of moderate-to-severe acne [OR (95% CI) = 2.33 (1.09, 4.99)] in daughters with or without irregular menstrual cycles. We found no associations of the mixture of six PFAS with PCOS or related traits.

Conclusion: Our findings suggest a positive association between maternal concentrations of EtFOSAA and PCOS in their daughters during mid-to-late adolescence, although future studies with larger sample size and extended follow-up across the reproductive life-course are needed.

Keywords: Androgen excess; Endocrine disrupting chemicals; Menstrual cycle; Ovulatory dysfunction; PFAS; Polycystic ovary syndrome.