Maternal urinary phthalate metabolites in relation to gestational diabetes and glucose intolerance during pregnancy

Background: Phthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes (GDM). Objective: We evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest. Study design: We used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) ("T1T3avg") phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing. Results: In our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 +/- 27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM ([OR (95% CI) per IQR increase] T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n=35). Conclusion: In alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT.