SAT445 Exposure To Perfluoroalkyl Substances At Preconception In Association With Metabolic Phenotype In Women From Singapore

Disclosure: N.J. Cohen: None. M. Yao: None. V. Midya: None. S. India-Aldana: None. S.S. Andra: None. S. Narasimhan: None. A.K. Meher: None. M. Arora: None. J.K. Chan: None. S.Y. Chan: None. Y. Kway: None. N. Michael: None. S.A. Sadanathan: None. J.G. Eriksson: None. S.S. Velan: None. T.K. Hian: None. Y. Oulhote: None. J. Huang: None. D. Valvi: None. Background and Aim: Exposure to perfluoroalkyl substances (PFAS) may result in adverse metabolic health outcomes, but few studies have focused on preconception PFAS exposures and metabolic dysregulation which could impact pregnancy. We assessed cross-sectional and prospective associations between preconception PFAS concentrations and glucose regulation, insulin sensitivity, and magnetic resonance imaging (MRI) based adiposity measures in a Singaporean cohort of women who were actively attempting to conceive. Methods: Our analyses included 384 participants from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), from which 126 underwent abdominal MRI at preconception. 15 different PFAS in preconception plasma samples were measured, and metabolic measures were cross-sectionally assessed at preconception (waist-to-height ratio [WHtR], 2-hour oral glucose tolerance test [OGTT] indices, and MRI-based measures of abdominal adiposity and liver fat), and prospectively at 24-28 weeks of gestation (2-hour OGTT indices). We used linear regression models to assess associations between individual PFAS and metabolic phenotype at preconception and pregnancy. In addition, we used Bayesian weighted quantile sum (BWQS) regression to assess the joint associations of the PFAS mixture with study outcomes. Results: We observed negative associations between perfluorononanoic acid (PFNA) concentrations and visceral adipose tissue (VAT; log(2)-transformed) volume (β per doubling of PFNA=-0.12 cm(3), 95% CI -0.24, 0.00) and log(2)-transformed liver fat percentage (β=-0.28%, 95% CI -0.52, -0.04). Inverse associations were observed between the individual PFAS and most mid-pregnancy OGTT indices and insulin resistance, but were not statistically significant. Associations were not statistically significant for all preconception OGTT indices. Conclusions: We did not find strong evidence for an association between preconception PFAS concentrations and prenatal metabolic outcomes in young women in Singapore. Cross-sectional analyses indicated reduced adiposity in VAT volume and liver fat percentage with increasing PFAS concentration, which requires further investigation in prospective, more diverse, and larger studies. Presentation: Saturday, June 17, 2023