The associations of phthalate biomarkers during pregnancy with later glycemia and lipid profiles

Background: Pregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy.

Objectives: To examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health.

Design: We quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4-5 and 6-8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models.

Results: As a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: -0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: -0.08 SD, 95%CrI: -0.16, -0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL.

Conclusions: Phthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed.