Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones

PLoS One. 2016 Jul 25;11(7):e0159398. doi: 10.1371/journal.pone.0159398. eCollection 2016.


Introduction: Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy.

Method: We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethylhexyl) phthalate (MEHP), mono-butyl phthalate (MnBP), of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG).

Results: Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates) of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction.

Conclusion: We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

MeSH terms

  • Adult
  • Amniotic Fluid / metabolism
  • Biomarkers
  • Creatinine / blood
  • Endocrine Disruptors*
  • Environmental Exposure*
  • Female
  • Gestational Age
  • Humans
  • Maternal Exposure*
  • Menarche
  • Metabolomics
  • Phthalic Acids* / adverse effects
  • Pregnancy
  • Public Health Surveillance
  • Thyroid Hormones / blood*


  • Biomarkers
  • Endocrine Disruptors
  • Phthalic Acids
  • Thyroid Hormones
  • phthalic acid
  • Creatinine

Grant support

This study was supported by National Health Research Institutes grant, EH-102-PP-01, EH-103-PP-02, EH-104-PP05. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.