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Urinary Concentrations of Phthalate Metabolites and Pregnancy Loss Among Women Conceiving with Medically Assisted Reproduction

Messerlian, Carmen; Wylie, Blair J.; Mínguez-Alarcón, Lidia; Williams, Paige L.; Ford, Jennifer B.; Souter, Irene C.; Calafat, Antonia M.; Hauser, Russ; for the Earth Study Team

doi: 10.1097/EDE.0000000000000525
Perinatal Epidemiology

Background: Animal studies demonstrate that several phthalates are embryofetotoxic and are associated with increased pregnancy loss and malformations. Results from human studies on phthalates and pregnancy loss are inconsistent.

Methods: We examined pregnancy loss prospectively in relation to urinary phthalate metabolite concentrations among women undergoing medically assisted reproduction. We used data from 256 women conceiving 303 pregnancies recruited between 2004 and 2012 from the Massachusetts General Hospital Fertility Center. We quantified 11 phthalate metabolite concentrations and calculated the molar sum of four di(2-ethylhexyl) phthalate (DEHP) metabolites (ΣDEHP). We estimated risk ratios (RRs) and 95% confidence intervals for biochemical loss and total pregnancy loss (<20 weeks’ gestation) across quartiles using repeated measures log-binomial models, adjusted for age, body mass index, smoking and infertility diagnosis.

Results: Of the 303 pregnancies, 83 (27%) ended in loss less than 20 weeks’ gestation and among these, 31 (10%) ended in biochemical loss. Although imprecise, the RRs for biochemical loss increased across quartiles of ΣDEHP and three individual DEHP metabolites. For ΣDEHP, the RRs (confidence intervals) were 2.3 (0.63, 8.5), 2.0 (0.58, 7.2), and 3.4 (0.97, 11.7) for quartiles two, three, and four, compared with one, respectively (P trend = 0.04). RRs for total pregnancy loss were elevated in the highest quartiles of ΣDEHP and three DEHP metabolites. The remaining seven phthalate metabolite concentrations evaluated were not associated with either outcome.

Conclusions: We found a suggestive pattern of association between conception cycle-specific urinary concentrations of DEHP metabolites and biochemical and total pregnancy loss among women undergoing medically assisted reproduction.

From the aDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA; bDivision of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; cDepartment of Biostatistics, dDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; eMassachusetts General Hospital Fertility Center, Department of Obstetrics and Gynecology, Harvard Medical School, Boston, MA; fNational Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA; and gVincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Submitted 13 October 2015; accepted 6 June 2016.

This work is supported by Grants ES009718, ES022955, and ES000002, T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS). BJW was supported by the National Institute of Environmental Health Sciences (NIH K23 ES021471). CM was supported by a post-doctoral fellowship award from the Canadian Institutes of Health Research.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). The use of trade names and commercial sources is for identification only and does not constitute endorsement by the US Department of Health and Human Services or CDC.

The authors report no conflicts of interest.

Correspondence: Carmen Messerlian, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, FXB 102A, Boston, MA 02115. E-mail: cmesser@hsph.harvard.edu.

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