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

Abstract

IntroductionPrevious 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.MethodWe 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).ResultsThree 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.ConclusionWe 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.

Urinary phthalate metabolite concentrations and maternal weight during early pregnancy

“…Of the studies that have evaluated this question, one study found positive associations with MnBP, and MBzP (Song et al 2014), while another found inverse cross-sectional associations with MEHP (Hatch et al 2008). Recent studies have investigated phthalate exposure during pregnancy as it relates with the risk of major pregnancy complications such as gestational diabetes and preterm birth (James-Todd et al 2016; Huang et al 2016; Philips et al 2016; Ferguson et al 2014; Ferguson et al 2015; Werner et al 2015). While studies have evaluated pregnancy phthalate metabolite concentrations, to our knowledge, this is among the first study to focus on maternal obesity measures as a primary outcome.…”

Effects of Prenatal Phthalate Exposure on Thyroid Hormone Concentrations Beginning at The Embryonic Stage

“…Previous animal studies showed that rats fed DEHP through the diet displayed histopathologic alterations in the thyroid indicative of hyperactivity, increased thyroglobulin turn over, and significantly decreased plasma T 4 concentrations 13,32–34 . A few epidemiological studies explored the associations of prenatal phthalates exposure with maternal thyroid function, which was assessed by metabolites concentrations in urine samples 13,16,25–28 . Three studies reported that maternal phthalates exposures (e.g., MBP, MBzP, MEHP and MEHHP) were associated with reduced concentrations of TT4 13,25,28 , which were consistent with our results.…”

“…A few epidemiological studies explored the associations of prenatal phthalates exposure with maternal thyroid function, which was assessed by metabolites concentrations in urine samples 13,16,25–28 . Three studies reported that maternal phthalates exposures (e.g., MBP, MBzP, MEHP and MEHHP) were associated with reduced concentrations of TT4 13,25,28 , which were consistent with our results. However, Johns et al .…”

“…To date, a few studies have reported the potential association of phthalate exposure with thyroid function in pregnant women 13,16,25–28 . Huang et al .…”

“…Huang et al . (2007; 2016) 13,28 found urinary monobutyl phthalate (MBP) exposure was negatively associated with serum total thyroxine (TT4) and FT4 in early pregnancy. Johns et al .…”