Abstract
BackgroundSubfertile women are at increased risk of glucose intolerance in pregnancy. Based on epidemiologic studies, exposure to certain phthalates is associated with diabetes, elevated glucose, and increased insulin resistance.ObjectivesTo evaluate the association between urinary phthalate metabolites and pregnancy glucose levels in women seeking medically assisted reproduction.MethodsWe evaluated 245 women participating in a prospective cohort study based at a large fertility clinic who delivered live births and had data on pregnancy urinary phthalate metabolite concentrations and blood glucose levels. Urinary phthalate metabolite concentrations were from single spot urine samples collected in 1st and 2nd trimesters. Blood glucose data was abstracted from medical records for non-fasting 50-g glucose challenge tests at 24–28 weeks gestation. Multivariable linear regression models were used to evaluate associations between 7 urinary phthalate metabolites in quartiles and mean glucose adjusted for potential confounders.ResultsEighteen percent of women had glucose levels ≥ 140 mg/dL. Second trimester monoethyl phthalate (MEP) concentrations were positively associated with glucose levels, with adjusted mean (95%CI) glucose levels of 121 mg/dl (114, 128) vs. 109 mg/dL (103, 116) for women in highest and lowest quartiles, respectively. Women in the highest quartile of second trimester mono-isobutyl phthalate (MiBP) concentrations had a mean glucose level 14 mg/dL lower compared to women in the lowest quartile. No other urinary phthalate metabolites were associated with glucose levels.ConclusionsMEP and MiBP—metabolites of diethyl phthalate and dibutyl phthalate, respectively—were associated with higher pregnancy glucose in subfertile women—a population at high risk of glucose intolerance in pregnancy.
Highlights
Subfertile women are at increased risk of glucose intolerance in pregnancy
We excluded 85 women with only one urine sample collected. In this subset of 159 women with prospectively collected urine samples with urinary phthalate metabolite concentrations measured at both 1st and 2nd trimesters, we evaluated the associations between trimester-specific urinary phthalate metabolites and glucose levels from the glucose challenge test (GCT)
A total of 245 women, representing ~ 60% of the overall Environment and Reproductive Health (EARTH) Study population, had data on urinary phthalate metabolites in the first or second trimester, as well as glucose information from the 50-g GCT conducted as a part of the Gestational diabetes mellitus (GDM) screening test
Summary
Subfertile women are at increased risk of glucose intolerance in pregnancy. Exposure to certain phthalates is associated with diabetes, elevated glucose, and increased insulin resistance. A growing body of literature suggests that any form of pregnancy hyperglycemia could lead to adverse outcomes, even without overt GDM [7, 8]. Women with elevated glucose levels, even without meeting the clinical criteria for GDM, are at increased risk of a variety of. While lifestyle factors are considered important determinants of pregnancy hyperglycemia [10], some studies suggest that environmental factors such as endocrine disrupting chemicals (EDCs) might be involved in hyperglycemia and diabetes [11,12,13,14,15]. Phthalates are ubiquitous with over 90% of the U.S, European, and Canadian populations having detectable urinary concentrations of phthalate biomarkers [18,19,20,21,22]
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