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Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

ABSTRACT: Limited evidence revealed conflicting results on relationship between phthalate exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort study in Chinese pregnant women (n?=?3220) was conducted to investigate the association between urinary phthalate metabolites and clinical pregnancy loss (gestational weeks 6 to 27; n?=?109). Morning urine samples during gestational weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The concentrations of low- and high-molecular weight phthalate metabolites (?LMWP <250?Da and ?HMWP >250?Da) were calculated. Adjusted logistic regression models showed increased risks of clinical pregnancy loss in women with higher creatinine- normalized concentrations of MEP, MBP, MEOHP, MEHHP, ?LMWP and ?HMWP. Stratified analysis by gestational weeks (10 weeks) of miscarriage indicated positive associations of MEP, MEOHP, MEHHP and ?HMWP with embryonic loss (during gestational weeks 6 to 10). The only association of foetal loss (during gestational weeks 11 to 27) was observed with MEHHP. Our findings suggested that Chinese women who were exposed to phthalates during early pregnancy had an increased risk of clinical pregnancy loss, especially embryonic loss.

SUBMITTER: Gao H

PROVIDER: S-EPMC5533765 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

Gao Hui H Zhang Yun-Wei YW Huang Kun K Yan Shuang-Qin SQ Mao Lei-Jing LJ Ge Xing X Xu Ye-Qing YQ Xu Yuan-Yuan YY Sheng Jie J Jin Zhong-Xiu ZX Zhu Peng P Tao Xu-Guang XG Hao Jia-Hu JH Tao Fang-Biao FB

Scientific reports 20170728 1

Limited evidence revealed conflicting results on relationship between phthalate exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort study in Chinese pregnant women (n = 3220) was conducted to investigate the association between urinary phthalate metabolites and clinical pregnancy loss (gestational weeks 6 to 27; n = 109). Morning urine samples during gestational weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP), monoethyl phthalate (MEP ...[more]

PMID: 28754983

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Project description:BACKGROUND:Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development. OBJECTIVE:To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception. METHODS:We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG. RESULTS:Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6-8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) =?2.8 (1.2, 6.7) and OR (CI) =?2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10-12 days vs. 9 days); OR (CI) =?1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p?=?0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (?DEHP) (p?=?0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) =?2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) =?1.6 (0.9, 2.8); no rise vs. early rise). CONCLUSIONS:The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted.

Project description:BackgroundEnvironmental exposure to phthalates and bisphenol A (BPA) may have endocrine disrupting effects that alter length of gestation. We assessed the association between the urinary concentrations of 11 phthalate metabolites and BPA with length of gestation in a cohort of women followed from before conception with daily 1st-morning urinary hormone measures that identified day of implantation.MethodsPre-implantation and post-implantation urinary phthalate metabolites and BPA concentrations were measured in pooled urine samples designed to limit single-measure variability due to the likely episodic nature of these exposures and the short half-life of these compounds. We estimated associations between these exposure biomarkers early in pregnancy with length of gestation from implantation to spontaneous birth. Cox proportional hazards models were used to estimate the hazard of birth among 125 naturally-conceived, singleton live births with censoring for medical interventions that artificially shortened pregnancy.ResultsHigher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (a metabolite of di (2-ethylhexyl) phthalate (DEHP)) during the pre-implantation window were associated with reduced probability of birth, i.e., longer gestations (hazard ratio (HR): 0.55, 95% CI: 0.35, 0.86; p = 0.01). The HR for the molar sum of the four DEHP metabolites measured showed a similar association (HR: 0.67, 95% CI: 0.43, 1.05). Higher concentrations of mono (3-carboxypropyl) phthalate (MCPP), a non-specific metabolite of several high molecular-weight phthalates, measured post-implantation were associated with increased risk of earlier birth, i.e. shorter length of gestation, HR: 1.59, CI: 1.02, 2.49.ConclusionsEarly gestational exposure to DEHP and possibly other high-molecular weight phthalates, (as reflected by urinary MCPP concentrations) may influence the length of pregnancy. Such effects could have consequences for neonatal and maternal health.

Project description:BackgroundPreeclampsia represents a major cause of maternal mortality and morbidity worldwide. Although it is known that the placenta plays a central role in development of preeclampsia, investigation into the contribution of environmental toxicants to the risk of preeclampsia has been sparse.ObjectivesIn the present study we examined the relationship between longitudinally measured urinary BPA and phthalate metabolite concentrations during gestation and preeclampsia.MethodsA nested case-control study of preterm birth was performed in 2011 from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston. There were 50 cases of preeclampsia as part of this study. Urine samples were analyzed for concentrations of BPA and nine phthalate metabolites several times during pregnancy. Adjusted Cox proportional hazard models were used to calculate hazard ratios of preeclampsia in association with an interquartile range increase in BPA and phthalate concentrations and were weighted to reflect results generalizable to the base population.ResultsAdjusted hazard ratios indicated that an interquartile range increase of urinary concentrations of BPA (1.53; 95% CI: 1.04, 2.25) and MEP (monoethyl phthalate) (1.72; 95% CI: 1.28, 2.30) at 10 weeks gestation was associated with onset of preeclampsia, whereas significantly elevated hazard ratios were found across gestation for all DEHP [di(2-ethylhexyl) phthalate] metabolites. These relationships differed based on infant sex.ConclusionsUrinary concentrations of BPA and several phthalate metabolites were significantly associated with increased risk of preeclampsia. If validated, these results indicate an environmental contribution of endocrine-disrupting chemicals to preeclampsia and suggest a modifiable means to reduce the mortality and morbidity associated with this condition.CitationCantonwine DE, Meeker JD, Ferguson KK, Mukherjee B, Hauser R, McElrath TF. 2016. Urinary concentrations of bisphenol A and phthalate metabolites measured during pregnancy and risk of preeclampsia. Environ Health Perspect 124:1651-1655;?http://dx.doi.org/10.1289/EHP188.

Dataset Information

Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

Publications

Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

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