Maternal Urinary Organophosphate Esters and Alterations in Maternal and Neonatal Thyroid Hormones

Abstract

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed.

Keywords: cohort studies; flame retardants; pregnancy; thyroid hormones.

Figure 1

Line plot of multiple informant model results with 3 time points of creatinine standardized and ln-transformed, maternal urinary organophosphate metabolite measurements in association with newborn cord blood thyroid hormone concentrations in the Health Outcomes and Measures of the Environment (HOME) study, 2003–2006. Models were adjusted for mother’s age at delivery, mother’s education, race, year of birth, and infant sex. Levels of A) bis-2-chloroethyl phosphate (BCEP) and free triiodothyronine (T3; pg/mL); B) BCEP and free thyroxine (T4; ng/dL); C) BCEP and total T3 (ng/dL); D) BCEP and total T4 (μg/dL); E) BCEP and log of thyroid-stimulating hormone (TSH; μIU/mL); F) bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and free T3 (pg/mL); G) BDCIPP and free T4 (ng/dL); H) BDCIPP and total T3 (ng/dL); I) BDCIPP and total T4 (μg/dL); J) BDCIPP and log-TSH (μIU/mL); K) diphenyl phosphate (DPHP) and free T3 (pg/mL); L) DPHP and free T4 (ng/dL); M) DPHP and total T3 (ng/dL); N) DPHP and total T4 (μg/dL); O) DPHP and log-TSH (μIU/mL); P) DNBP and free T3 (pg/mL); Q) DNBP and free T4 (ng/dL); R) DNBP and total T3 (ng/dL); S) DNBP and total T4 (μg/dL); and T) DNBP and log-TSH (μIU/mL).