High maternal glucose exacerbates the association between prenatal per- and polyfluoroalkyl substance exposure and reduced birth weight

Background: Per- and polyfluoroalkyl substances (PFAS) exposure has been associated with reduced birth weight. However, the association may be complicated by glucose status due to PFAS impact on fetal growth and placental transport. Objectives: To examine whether maternal glucose status modifies the association between prenatal PFAS exposure and birth weight z-score. Methods: We analyzed data of 1405 mother-child pairs from the prospective Shanghai Birth Cohort. Plasma concentrations of six PFAS were quantified in the first trimester. Fasting plasma glucose (FPG) was collected at 24-28 gestation weeks. A range of FPG cutoffs (4.9-5.4 mmol/L) covering current recommendations for gestational diabetes mellitus were used to define high and low FPG groups. Association between PFAS concentration and birth weight z-score was evaluated using multivariate linear regression in two FPG groups respectively, and the dose-response relationship was estimated with cutoffs ranging from low to high. We then used propensity score to counterbalance the effects of different PFAS concentrations between the high and low FPG groups, and run the regression again. Results: A doubling increase in concentrations of several PFAS was inversely associated with birth weight z-score. The association was more evident in high FPG groups and the magnitudes intensified when FPG cutoff increased. The strongest association was observed for PFOA, with the magnitude increased from -0.34 (95 % CI: -0.66, -0.03) for 5.0 mmol/L cutoff, to -0.41 (95 % CI: -0.77, -0.05) for 5.1 mmol/L cutoff, and further to -0.51 (95 % CI: -0.98, -0.03) for 5.3 mmol/L. Propensity score matching yielded similar results. Conclusions: High maternal glucose level may increase the risk of reduced birth weight z-score related to prenatal PFAS exposure. Moreover, exploring the effects with different FPG cutoffs may contribute to providing intervention strategies for pregnant women with high PFAS exposure.