A Cohort Study On Association Of Phthalate Exposure During The First Trimester Of Pregnancy With Clinical Pregnancy Loss

ObjectiveTo investigate phthalate exposure in pregnant women during the first trimester of pregnancy in Ma’anshan city, China. To examine phthalate exposure during the first trimester of pregnancy in relation to clinical pregnancy loss. MethodsThe Ma’anshan-Anhui Birth Cohort(MABC) enrolled eligible pregnant women between May 2013 and September 2014 from Maternal and Child Health(MCH) Center in Ma’anshan City, Anhui Province, China. During their first antenatal care visit, each women completed a face-to-face questionnaire regarding maternal and paternal demographic characteristics. Meanwhile, first morning urine samples of pregnant women were collected for analyzing for seven phthalate metabolites. Specifically, monomethyl phthalate(MMP), monoethyl phthalate(MEP), monobutyl phthalate(MBP), and monobenzyl phthalate(MBz P) were the metabolites of dimethyl phthalate(DMP), diethyl phthalate(DEP), dibutyl phthalate(DBP), and butyl benzyl phthalate(BBz P), respectively. Mono(2-ethylhexyl) phthalate(MEHP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), and mono(2-ethyl-5-hydroxylhexyl) phthalate(MEHHP) were the metabolites of di(2-ethylhexyl) phthalate(DEHP). According to the molecular weight of monoesters, the former three metabolites were categorized into low molecular weight phthalates(LMWPs, <250Da), and the later four metabolites were categorized into high molecular weight phthalates(HMWPs, >250Da). All participant cases were then prospectively followed until their delivery or other birth outcomes. Of the 3 474 women recruited in MABC, 254 were excluded for ectopic pregnancy(n = 2), stillbirth(n = 10), therapeutic abortion(n = 30), multiple gestation(n = 39), and unavailability of urine specimens(n = 173), leaving 3 220 for whom data were available. Urinary concentrations of seven phthalate metabolites were decribed as volume-based concentrations and creatinine-adjusted concentrations. Moreover, logistic regression analyses were used to examine the association between urinary volume-based and creatinine-adjusted concentrations of metabolites and the clinical pregnancy loss. Clinical pregnancy loss(conception lasting > 6 weeks) was further classified into embryonic loss(EL, 6-10 weeks of gestation) and foetal loss(FL, 11-27 weeks of gestation). Stratification analyses were used to explore the association of urinary metabolite cocnentrations with EL and FL. ResultsAll phthalate metabolites were detectable in 99.12-99.84% of the 3220 urine samples, except for MBz P, which was detectable in only 63.93% of the urine samples. The concentration of MBP was highest, followed by that of MMP and MEP, whereas that of MBz P was the lowest. The concentration of LMWPs was 10-fold higher than that of HMWPs.Univariate logistic regression analyses showed that increased volume-based concentrations of MEHHP(RR = 1.67,95%CI: 1.04-2.69) and DEHP(RR = 1.81, 95%CI: 1.11-2.95) were positively associated with a risk of pregnancy loss(P < 0.05). Increased creatinine-adjusted concentrations of MEP(RR = 1.68, 95%CI: 1.02-2.75), MBP(RR = 1.61,95%CI: 1.01-2.59), MEOHP(RR = 1.75, 95%CI: 1.09-2.81), MEHHP(RR = 2.29, 95%CI: 1.37-3.81), DEHP(RR = 1.66, 95%CI: 1.05-2.64), and HMWPs(RR = 1.79, 95%CI: 1.11-2.86) were positively associated with a risk of clinical pregnancy loss(P < 0.05). The mentioned RR values were still statistically significant(P < 0.05) after adjusting for potential confounders including maternal age, gestational age, gravity, primipara, and paternal smoking status.After adjusting for potential confounders including maternal age, gravity, primipara, and paternal smoking status, stratification analyses revealed that increased volume-based concentrations of MBz P(RR = 2.18,95%CI: 1.18-4.04), MEHHP(RR = 1.87,95%CI: 1.01-3.47), and DEHP(RR = 2.18, 95%CI: 1.14-4.15) were positively associated with a risk of EL(P < 0.05). Increased creatinine-adjusted concentrations of MEP(RR = 2.02, 95%CI: 1.05-3.89), MEOHP(RR = 2.08,95%CI: 1.09-3.98), MEHHP(RR = 2.11, 95%CI: 1.08-4.13), and HMWPs(RR = 2.10, 95%CI: 1.09-3.99) were positively associated with a risk of EL(P < 0.05). Only the creatinine-adjusted concentration of MEHHP(RR = 2.45, 95%CI: 1.12-5.38) was associated with a risk of FL(P < 0.05). ConclusionThe widespread exposure of pregnant women in Ma’anshan city of China to phthalate pollutants(DBP, DMP, DEP and DEHP), particularly LMWPs(DBP, DMP and DEP) could be suggested. Moreover, our results suggested phthalates exposure should be an independent risk factor for clinical pregnancy loss, and embryonic loss(6-10 gestational weeks) is more sensitive to these chemicals.