1. Academic Validation
  2. Periconception bisphenol and phthalate concentrations in women and men, time to pregnancy, and risk of miscarriage

Periconception bisphenol and phthalate concentrations in women and men, time to pregnancy, and risk of miscarriage

  • Environ Res. 2025 Aug 1:278:121712. doi: 10.1016/j.envres.2025.121712.
Sophia M Blaauwendraad 1 Aline J Boxem 2 Romy Gaillard 2 Linda G Kahn 3 Mathusa Lakuleswaran 3 Amrit Kaur Sakhi 4 Eline L Bekkers 2 Zixuan Mo 5 Larry Spadacini 5 Cathrine Thomsen 4 Eric Ap Steegers 6 Annemarie Gmgj Mulders 6 Vincent Wv Jaddoe 2 Leonardo Trasande 7
Affiliations

Affiliations

  • 1 The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: [email protected].
  • 2 The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • 3 Departments of Pediatrics and Population Health, New York University School of Medicine, New York, NY, United States.
  • 4 Department of Food Safety, Norwegian Institute of Public Health, Norway.
  • 5 Departments of Pediatrics and Environmental Medicine, New York University School of Medicine, New York, NY, United States.
  • 6 Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • 7 Departments of Pediatrics and Environmental Medicine, New York University School of Medicine, New York, NY, United States; New York University Wagner School of Public Service, New York City, NY, United States.
Abstract

Background: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates might lead to adverse fertility and early pregnancy outcomes.

Methods: This study was embedded in the Generation R Next Study, a population-based cohort study from preconception onwards. Urinary phthalate and bisphenol concentrations were assessed in the preconception period (938 women), defined as the period in which couples were actively trying to conceive, and early pregnancy (1,366 women and 1,202 men, mean gestational age at sampling 8·6 weeks). Time to pregnancy and miscarriage were assessed using questionnaires and ultrasounds. Subfertility was defined as the inability to conceive within 12 months or need for assisted reproductive technologies.

Findings: Higher preconception urinary bisphenol S (BPS) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (mCOCH) concentrations in women were associated with longer time to pregnancy. Higher preconception mono-[(2-carboxymethyl)hexyl] phthalate, mono-2-ethyl-5-oxohexyl phthalate (mEOHP), mono-(7-carboxy-n-heptyl)phthalate (mCHpP), and mono benzyl phthalate (mBzBP) were associated with shorter time to pregnancy, and higher mono-2-ethyl-5-hydroxyhexyl phthalate (mEHHP), mEOHP, and mBzBP with lower odds of subfertility. In men, higher early pregnancy BPS, mCHpP, mono-4-methyl-7-hydroxyoctyl phthalate, mono-4-methyl-7-oxooctyl phthalate, and mono-ethyl phthalate were associated with shorter time to pregnancy or lower odds of subfertility. Higher preconception or early pregnancy BPS, phthalic acid, and mCHpP in women were associated with lower odds of miscarriage, whereas higher mono-carboxy-isoctyl phthalate, mCOCH, and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cxmPHxP) with higher odds of miscarriage (all p-values <0·05).

Interpretation: Preconception and early pregnancy exposure to bisphenols and phthalates may affect couple fertility. Our results should be considered as hypothesis generating and replicated in future studies, possibly including repeated chemical measurements and mixture analysis.

Keywords

Bisphenols; Miscarriage; Phthalates; Time to pregnancy.

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