Association of urinary phthalate metabolite concentrations with inflammatory biomarker levels among pregnant women

Environ Res. 2025 Aug 15;279(Pt 2):121911. doi: 10.1016/j.envres.2025.121911. Epub 2025 May 20.

Abstract

Background: Few studies have evaluated the associations between phthalate exposures and maternal inflammation.

Objectives: To examine cross-sectional associations of urinary phthalate metabolites, individually and as a mixture, with serum inflammatory biomarkers during pregnancy.

Methods: A total of 175 pregnant women enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 were included. Concentrations of 11 urinary phthalate metabolites and two serum inflammatory biomarkers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured. Urinary concentrations of phthalate metabolites were adjusted for specific gravity (SG) before analysis. Linear regression and Bayesian Kernel Machine Regression models were used to examine the associations for individual phthalates and their mixture, respectively. Stratified analyses by pre-pregnancy body mass index (BMI) were also conducted.

Results: No association for urinary phthalate metabolites, individually or as a mixture, was observed with serum CRP overall among pregnant women. Urinary mono-3-carboxypropyl phthalate and monocarboxyisooctyl phthalate were positively associated with serum IL-6 (β [95 % CI] per 1-SD increase in log-transformed, SG-adjusted concentrations: 0.09 [0.01, 0.16] and 0.09 [0.02, 0.17], respectively). Besides, urinary mono-isobutyl phthalate was positively associated with serum IL-6 among women with a pre-pregnancy BMI ≥25 kg/m2 (β [95 % CI] per 1-SD increase: 0.15 [0.00, 0.30]), but not with lower BMI (-0.03 [-0.12, 0.07]). A suggestive positive association between phthalate mixture and serum IL-6 was observed in the high pre-pregnancy BMI group.

Conclusions: Our findings suggest that women with a higher pre-pregnancy BMI may be more vulnerable to the effects of certain phthalates on maternal inflammation reflected by IL-6.

Keywords: Inflammation; Mixture; Phthalate; Pregnancy.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Environmental Pollutants* / urine
  • Female
  • Humans
  • Inflammation* / blood
  • Interleukin-6 / blood
  • Phthalic Acids* / urine
  • Pregnancy
  • Young Adult

Substances

  • Phthalic Acids
  • Biomarkers
  • C-Reactive Protein
  • Interleukin-6
  • Environmental Pollutants
  • phthalic acid