Exposure to elevated per- and polyfluoroalkyl substances in early pregnancy is related to increased risk of gestational diabetes mellitus: A nested case-control study in Shanghai, China

Background: Long-chain per- and polyfluoroalkyl substances (PFASs) and their short-chain alternatives have been produced and used extensively in China. However, it is unclear whether these compounds contribute to the risk of gestational diabetes mellitus (GDM) in women residing in contaminated areas. Objective: The study was performed to explore the association between PFASs varying in chain length and the risk of developing GDM. Method: A nested case-control study was conducted in a prospective cohort of 2,460 pregnant women between July 1, 2017, and January 31, 2019 in Shanghai, China. Twelve PFASs of interest were measured using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) in the sera of pregnant women at 16-20 weeks. GDM was diagnosed by an oral glucose tolerance test administered over 24-28 gestational weeks. The cases and controls were matched by maternal age. The relationship between maternal serum PFAS level and GDM risk was determined by conditional logistic and linear regression analyses. Results: A total of 165 GDM cases and 330 controls were enrolled in the study cohort. The frequencies of detection of PFHpA, PFDS, and PFOSA were all <= 80%. Hence, they were excluded from any further risk analysis. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected at relatively high serum levels (medians 6.57 ng/mL and 8.07 ng/mL, respectively). The serum levels of perfluorobutanesulfonic acid (PFBS) and perfluorododecanoic acid (PFDoA) were significantly higher in the GDM group than they were in the control group (P = 0.02 and P < 0.01, respectively) according to a nonparametric Wilcoxon rank sum test. A quartile analysis showed that the odds ratio of GDM would significantly increase at the highest PFBS and PFDoA levels. In the core model, the adjusted ORs were 2.02 (95% CI = 1.04-3.79) and 13.00 (95% CI = 4.74-24.59), respectively, after adjusting for maternal age, sampling time, parity and body mass index [BMI]). Conclusion: Elevated maternal serum PFBS and PFDoA levels in early pregnancy may be associated with a substantially higher GDM risk.