Associations of individual and cumulative urinary phthalate and replacement biomarkers with gestational weight gain through late pregnancy

Diana C. Pacyga, Marisa A. Patti, George D. Papandonatos, Diana K. Haggerty, Antonia M. Calafat, Joseph C. Gardiner, Joseph M. Braun, Susan L. Schantz, Rita S. Strakovsky

Research output: Contribution to journalArticlepeer-review


Background/aims: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) – a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. Methods: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. Results: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (ƩDEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (ƩDiNCH), and di(2-ethylhexyl) terephthalate (ƩDEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified ƩDEHP, ƩDEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (ƩDiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (β: −0.29; 95% CI: −0.70, 0.12). In women carrying females, ƩDEHP contributed to the marginal inverse joint association (β: −0.54; 95% CI: −1.09, 0.03). However, there was no overall association in women carrying males (β: 0.00; 95% CI: −0.60, 0.59), which was explained by approximately equal negative (driven by ƩDEHTP) and positive (driven by ƩDiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. Conclusions: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because ƩDEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.

Original languageEnglish (US)
Article number158788
JournalScience of the Total Environment
StatePublished - Jan 10 2023


  • DiNCH
  • Fetal sex
  • Gestational weight gain
  • Phthalates
  • Pregnancy

ASJC Scopus subject areas

  • Pollution
  • Waste Management and Disposal
  • Environmental Engineering
  • Environmental Chemistry


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