Endocrine Abstracts

JOINT1322

Background: Aldosterone is an independent predictor of higher placenta weight and birth weight. Accordingly, mice studies demonstrated aldosterone to have essential trophic effects on fetoplacental growth. Perfluoroalkyl substances (PFAS) are synthetic endocrine disrupting chemicals of high persistency. PFAS have been suggested as an inducer of aldosterone secretion in adrenocortical cells. However, there is no available in vivo data on PFAS exposure and 24-hour (h) urine (U-) aldosterone levels.

Objective: To investigate associations between first trimester PFAS concentrations and levels of 24-h U-aldosterone in third trimester.

Methods: In Odense Child Cohort (OCC), serum (S-) concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were assessed in 1, 611 eligible women at median gestational week (GW) 12 (25^th, 75^th percentile: 10, 15). Among these, 24-h U-aldosterone was available in 469 women at median GW 29 (25^th, 75^th percentile: 28, 29). Multiple linear regression models were performed to estimate associations between S-PFAS concentrations (both as continuous and categorized data) and 24h U-aldosterone levels in pregnancy.

Results: Included women had a mean age of 30. 1 (± 4. 5 SD) years, were predominantly nulliparous (58. 5%) with a median pre-pregnancy BMI of 24. 9 (5^th, 95^th percentiles: 19. 6, 36. 1) kg/m². In adjusted analyses, a doubling in S-concentrations of PFOS, PFOA, and PFNA were associated with a decrease in 24h U-aldosterone levels by -4. 8 % (95% CI: -8. 4%, -1. 0%), -5. 9% (95% CI: -9. 1%, -2. 7%), and -6. 2% (95% CI: -9. 9%, -2. 4%), respectively. Compared to the first tertile, exposure of PFOS and PFOA in third tertile, and PFNA in the second and third tertile statistically significantly decreased concentrations of 24-h U-aldosterone. A statistically significant dose-response relationship was observed across exposure tertiles for PFOS, PFOA, and PFNA (P-value for linear trend<0. 01) in the association with 24-h U-aldosterone.

Conclusion and Perspectives: Higher exposure concentrations of PFOS, PFOA, and PFNA in first trimester were associated with lower concentrations of 24-h U-aldosterone in third trimester. Aldosterone is an essential trophic factor for fetoplacental development. PFAS concentrations during pregnancy have been associated with negative pregnancy outcomes, including pregnancy loss and low birth weight. Hence, our observed inverse association between PFAS and aldosterone may be an important mechanistic link for the potential implications of PFAS on fetal growth.