Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis

Abstract

BackgroundIncreasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with an elevated risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal serum thyroid (free thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin [SHBG]) hormone levels at multiple time points during pregnancy.MethodsPreliminary data (n = 106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We collected urine and serum sample at the first and third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation, respectively. To explore the longitudinal relationships between urinary phthalate metabolites and serum thyroid and sex hormone concentrations, we used linear mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal age. An interaction term was added to each LMM to test whether the effect of urinary phthalate metabolites on serum thyroid and sex hormone levels varied by study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted linear regression models by study visit.ResultsIn adjusted LMMs, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations at the third study visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit, significant inverse associations were observed between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and progesterone was consistent across study visits.ConclusionsIn this group of pregnant women, urinary phthalate metabolites may be associated with altered maternal serum thyroid and sex hormone levels, and the magnitude of these effects may depend on the timing of exposure during gestation.Electronic supplementary materialThe online version of this article (doi:10.1186/1477-7827-13-4) contains supplementary material, which is available to authorized users.

Paternal and maternal preconception urinary phthalate metabolite concentrations and child behavior

“…Furthermore, both animal and human studies show that phthalates can interfere with thyroid hormone action concentrations in pregnant women and children (Boas et al, 2012; Morgenstern et al, 2017; Yao et al, 2016). During pregnancy, higher urinary phthalate metabolite concentrations have been associated with higher gestational thyroid hormone concentrations (Johns et al, 2015). Thyroid hormone regulates early brain development processes such as the proliferation, migration and differentiation of neuronal cells (Bernal, 2005), and high-normal maternal thyroid hormone concentrations during early pregnancy are associated with lower IQ and lower gray matter volume in the child (Korevaar et al, 2016).…”

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

“…Ultrafiltration steps were conducted to separate free hormones, and then isotope dilution liquid chromatography tandem mass spectrometry was used to measure FT3 and FT4 as described previously (Johns et al, 2015; Kahric-Janicic et al, 2007; Soldin et al, 2004; Soldin and Soldin, 2011). A solid-phase immunochemiluminometric assay (DPC Immulite, Diagnostic Products Corporation) was used to measure TSH.…”

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes

“…The few studies published to date suggest conflicting results and focus on estrogen production during adult life. DEHP metabolites have been negatively associated with estradiol concentrations in adult female rodents and in ovarian granulosa cells via decreased aromatase transcription (28)(29)(30)(31)(32), but this relationship has not been observed in human studies (27,33,34). In contrast, DBP and BBzP exposures have been associated with increased estrogenicity in breast cancer cell lines and in vivo in offspring exposure in utero or in adult female rodent models (35)(36)(37).…”