Maternal organophosphate esters and sex steroid hormones in mid-pregnancy

Organophosphate esters (OPEs) are synthetic chemicals used in consumer products as flame retardants and plasticizers. OPEs are potential endocrine disruptors, but little is known regarding gestational OPE exposure and maternal sex steroid hormones in human pregnancy.

Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort participants (n=265) provided biospecimens and completed questionnaires in each trimester. In second trimester samples, we measured urinary OPE metabolite concentrations using HPLC-MS/MS. In second and third trimester serum samples, we measured sex steroids (total testosterone [TT], free testosterone, estrone [E1], estradiol [E2], and estriol [E3]) using LC-MS/MS. We fitted linear regression and linear mixed models examining each log-transformed, specific gravity-adjusted OPE metabolite in relation to sex steroid concentrations, adjusting for covariates. Three OPEs with >70% detection were considered continuously; six less prevalent metabolites were dichotomized (above vs below lower limit of detection). Secondary models were fit for male and female fetuses, separately. Results are shown as % difference in hormone levels.

Percent detection of OPEs ranged from 26% to 100%. Diphenyl phosphate (DPHP) had the highest concentration (median 0.9 ng/mL). Across trimesters 2 and 3, a log-unit increase in dibutyl phosphate/di-isobutyl phosphate (DBUP/DIBP) was associated with lower TT (%Δ = -6.6, 95%CI: 11.5, -1.5), E1 (%Δ = -5.6, 95%CI: 10.8, -0.1), and E2 (%Δ = -5.3, 95%CI: 8.2, -2.3). Compared to those with non-detectable levels, participants with detectable bis(methylphenyl) phosphate (BMPP) had lower E3 (%Δ = -45.9, 95%CI: 67.9, -8.9) and participants with detectable bis(2-chloroethyl) phosphate (BCETP) had lower E2 (%Δ = -1.4, 95%CI: 2.4, -0.4). Numerous associations were observed in trimesters 2 and 3, individually. We observed several differences by fetal sex that varied in magnitude and direction.

OPEs may act as endocrine disruptors by altering maternal sex steroid hormones during pregnancy, with some differences by fetal sex. Further research is needed to understand implications for maternal and child health.