Environmental Exposure to Perfluoroalkyl Substances in Early Pregnancy, Maternal Glucose Homeostasis and the Risk of Gestational Diabetes: A Prospective Cohort Study

Abstract

Background: Humans are widely exposed to environmental perfluoroalkyl substances ( PFAS ), which may alter glucose homeostasis . However, research linking PFAS exposure to glucose tolerance during pregnancy is limited and the results were inconsistent. We aimed to investigate the association between PFAS exposure and glucose homeostasis in pregnancy in a large prospective cohort. Methods: A total of 2747 pregnant women who participated in the Shanghai Birth Cohort, had blood samples in early pregnancy and completed a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks were included. 10 PFAS were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples in early pregnancy. Logistic regression was used to explore the associations between PFAS concentrations and gestational diabetes mellitus (GDM), while multiple linear regression was used to model the associations between PFAS and OGTT fasting, 1-h and 2-h glucose levels. Potential confounders were adjusted. Bayesian kernel machine regression (BKMR) and a quantile-based g-computation approach were employed to explore the joint and independent effects of PFAS on glucose homeostasis. Findings: The incidence of GDM was 11·8%. One log-unit increment in plasma concentrations in early pregnancy was associated with an increased risk of GDM for perfluorobutane sulfonate (PFBS) [adjusted odd ratio (aOR)=1·23, 95% confidence interval (95% CI): 1·05,1·44] and perfluoroheptanoic acid (PFHpA) (aOR=1·25, 95% CI: 1·07,1·46). Perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonate (PFHxS) and PFHpA were positively correlated with 1-h and 2-h glucose levels. Results of the mixed exposure model showed that the joint effects of PFAS were significantly associated with abnormal glucose homeostasis; PFOS, PFNA and PFHpA may be the main contributors. The above associations were more prominent among women with a normal prepregnant BMI. Interpretation: Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women. Funding Statement: This study was funded by the National Nature Science Foundation of China (41991314 and 81530086) and the Collaborative Innovation Program of the Shanghai Municipal Health Commission (2020CXJQ01), the Ministry of Science and Technology of China (2019YFA0802501), and supported in part by the National Human Genetic Resources Sharing Service Platform (2005DKA21300). Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: This project was approved by the Research Ethics Committees of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine.