Urinary phthalate and DINCH metabolite concentrations and gradations of maternal glucose intolerance

Background: Studies suggest a link between pregnancy phthalate exposures and gestational diabetes mellitus (GDM). Few studies have evaluated associations between phthalate biomarkers (individual or mixtures) with gradations of maternal glucose intolerance. Methods: In a subset of 606 women participating in LIFECODES pregnancy cohort, a combination of 50-gram 1-h non-fasting glucose load test (GLT) and 100-gram 3-h fasting oral glucose tolerance test was used to determine pregnancy glycemic status (median: 27 weeks gestation): normoglycemia (n = 136), impaired glucose tolerance (IGT) (n = 296), and GDM (n = 174). Nineteen metabolites of phthalates and their replacements were measured during each trimester. We used multivariable logistic regression models to evaluate associations between biomarkers (in quartiles) and maternal glycemic status (GDM v. normoglycemia and IGT v. normoglycemia), adjusting for potential confounders. We also used principal component analysis to evaluate associations jointly accounting for metabolites as chemical mixtures. Results: Higher 1st trimester mono-3-carboxypropyl phthalate (MCPP) was associated with decreased odds of GDM (Q4 v. Q1: 0.30; 95% CI: 0.13, 0.67) and IGT (Q4 v. Q1 OR: 0.37; 95% CI: 0.17, 0.79). Higher 2nd trimester mono-isobutyl phthalate (MiBP) was associated with increased IGT (Q4 v. Q1 OR: 2.07; 95% CI: 1.06, 4.07), and 2nd trimester mono-3-hydroxybutyl phthalate (MHBP) was non-monotonically associated with increased GDM (Q2 v. Q1 OR: 3.21; 95% CI: 1.54, 6.87). Mixture analyses showed similar associations (Q4 v. Q1 for 2nd trimester dibutyl phthalates metabotlites mixtures OR: 2.08; 95% CI: 1.04, 4.22). Conclusion: Some phthalate biomarkershad trimester-specific associations with glycemic outcomes, with long and short term health implications.