title: Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis.
abstract: BACKGROUND
  Increasing 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.
  
  
  METHODS
  Preliminary 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  In 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.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Johns
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Ferguson
authors.forename: Offie P
authors.initials: OP
authors.lastname: Soldin
authors.forename: David E
authors.initials: DE
authors.lastname: Cantonwine
authors.forename: Luis O
authors.initials: LO
authors.lastname: Rivera-González
authors.forename: Liza V Anzalota
authors.initials: LV
authors.lastname: Del Toro
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ye
authors.forename: Akram N
authors.initials: AN
authors.lastname: Alshawabkeh
authors.forename: José F
authors.initials: JF
authors.lastname: Cordero
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA. meekerj@umich.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D009035:Mothers; D010795:Phthalic Acids / Q000378:metabolism / Q000652:urine*; D010865:Pilot Projects; D011247:Pregnancy / Q000097:blood* / Q000652:urine*; D011647:Puerto Rico; D013963:Thyroid Hormones / Q000097:blood*; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D010795:Phthalic Acids; D013963:Thyroid Hormones; C032279:phthalic acid