Phthalate and DINCH urinary concentrations across pregnancy and risk of preterm birth

Preconception and prenatal exposure to phthalates has been associated with an increased risk of preterm birth. However, it is unclear whether there are periods of heightened susceptibility during pregnancy. This prospective cohort study included 386 women undergoing fertility treatment who gave birth to a singleton infant during 2005 through 2018. Eleven phthalate metabolites were measured in spot urine samples collected at each trimester. In approximately 50% of participants, two metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), a phthalate substitute, were also measured. The molar sum of four di(2-ethylhexyl) phthalate metabolites ( n-ary sumation DEHP) was calculated. We evaluated the associations of mean maternal biomarker concentrations with risk of preterm birth using modified log-binomial models and utilized multiple informant models to compare trimester-specific associations. We examined the relative biomarker concentration across gestation comparing women with preterm birth to women with term delivery using quadratic mixed model. The risk ratio for preterm birth associated with a one-unit increase in the natural log-transformed urinary concentrations of n-ary sumation DEHP (mean during pregnancy) was 1.21 (95% confidence interval (CI): 0.84, 1.72). In multiple informant models, these associations were strongest in the third trimester (RR = 1.51; 95% CI: 1.17, 1.95). Estimated mean n-ary sumation DEHP concentrations were higher among women with preterm than term delivery, especially late in gestation. Associations with preterm birth were also observed for each of the four individual DEHP metabolites. Detection of cyclohexane-1,2-dicarboxylic acid monocarboxyisooctyl ester (MCOCH), a metabolite of DINCH, appeared to be positively related to preterm birth. In this prospective cohort of subfertile couples, maternal n-ary sumation DEHP metabolite concentrations during pregnancy were associated with an increased risk of preterm birth, particularly during late gestation.

Automated summary

This study found that preconception and prenatal exposure to phthalates may increase the risk of preterm birth, particularly in late pregnancy, especially the DEHP metabolites. This suggests that these chemicals may have adverse effects on women's health and fetal development.