The Relationship of Preconception Urinary Phthalate Levels with Fecundability and Pregnancy Loss

Abstract

Background/Aim: Phthalates are endocrine disrupting chemicals widely used as plasticizers and in personal care products. In utero exposure has been linked to pregnancy complications, childhood developmental delay and male reproductive dysfunction; however, studies of impact on establishing pregnancy are limited.Methods: The EAGeR trial enrolled 1,228 women attempting pregnancy with 1-2 prior pregnancy losses and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. Pregnancy was assessed in each cycle using hCG testing and pregnancy loss determined when a positive hCG was followed by an observed loss. Twenty phthalate metabolites, including mono-(2-ethylhexyl) phthalate (mEHP), monobutyl phthalate (mBP) and monobenzyl phthalate (mBzP), were measured in a pooled sample of three consecutive daily spot urines from the beginning of the first menstrual cycle of follow-up to reduce exposure misclassification. Discrete-time survival and log-binomial models evaluated fecundability and pregnancy loss adjusting for creatinine and participant characteristics.Results: Phthalate concentrations were similar to other U.S. cohorts (e.g. median 6.6, interquartile range 4.1-12.4 ng/mL for mEHP). Overall, mEHP, mBP and mBzP were associated with lower fecundability (fecundability odds ratio [FOR] 0.90, 95% confidence interval [CI] 0.82-0.98 per log[mEHP]). Effect modification was observed by C-reactive protein (CRP) and body mass index (BMI), with mEHP, mEHP metabolites, mBP and mBzP associated with lower fecundability among those with higher CRP (FOR 0.77, 95% CI 0.65-0.90 for CRP≥1.95 mg/L and FOR 0.98, 95% CI 0.88-1.09 for CRP<1.95 mg/L per log[mEHP]) and higher BMI (FOR 0.69, 95% CI 0.56-0.85 for BMI≥30 kg/m2 and FOR 0.99, 95% CI 0.88-1.11 for BMI<25 kg/m2 per log[mEHP]). No relationship was observed between phthalates and pregnancy loss.Conclusions: Higher exposure to certain phthalates was associated with lower fecundability. Associations were strongest among women with higher BMI and inflammation, who may represent a key target group for screening and intervention.