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 (∑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 ∑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 ∑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 ∑DEHP metabolite concentrations during pregnancy were associated with an increased risk of
preterm birth, particularly during late gestation.