Associations of gestational exposure to organophosphate esters with gestational age and neonatal anthropometric measures: The HOME study

Abstract

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

Keywords: Gestational age; Organophosphate esters; Pregnancy outcomes; Preterm birth.

Figure 1.

Adjusted window-specific regression estimates (β and its 95% CI) between tertiles of maternal specific gravity standardized urinary OPE metabolites (μg/L) and gestational age (weeks) at birth. A. Overall associations: models adjusted for maternal age at delivery, race, household income, education, marital status, infant sex, parity, pre-pregnancy BMI, maternal serum cotinine concentrations at 16 weeks of gestation, and maternal blood lead levels at 16 weeks of gestation. P for trend tests the linear trend by assigning the median of each tertile of each OPE metabolite concentration. B (male) & C (female). Infant sex-specific associations: models adjusted for maternal age at delivery, race, household income, education, marital status, parity, pre-pregnancy BMI, maternal serum cotinine concentrations at 16 weeks of gestation, and maternal blood lead levels at 16 weeks of gestation. Cut-off points of the tertiles at 16 weeks were: 0.40 and 0.88 μg/L for BCEP, 0.51 and 1.13 μg/L for BDCIPP, 0.18 and 0.32 μg/L for DNBP, and 1.13 and 2.36 μg/L for DPHP; Cut-off points of the tertiles at 26 weeks were: 0.28 and 0.77 μg/L for BCEP, 0.34 and 0.82 μg/L for BDCIPP, 0.14 and 0.26 μg/L for DNBP, and 0.86 and 1.67 μg/L for DPHP. Abbreviations: Bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), and diphenyl phosphate (DPHP).

Figure 2.

Adjusted window-specific relative risks (RRs) and 95% confidence intervals for preterm birth across tertiles of maternal specific gravity standardized urinary OPE metabolite concentrations (μg/L). Models adjusted for maternal age at delivery, race, household income, education, marital status, infant sex, parity, pre-pregnancy BMI, maternal serum cotinine concentrations at 16 weeks of gestation, and maternal blood lead levels at 16 weeks of gestation. Cut-off points of the tertiles at 16 weeks were: 0.40 and 0.88 μg/L for BCEP, 0.51 and 1.13 μg/L for BDCIPP, 0.18 and 0.32 μg/L for DNBP, and 1.13 and 2.36 μg/L for DPHP; Cut-off points of the tertiles at 26 weeks were: 0.28 and 0.77 μg/L for BCEP, 0.34 and 0.82 μg/L for BDCIPP, 0.14 and 0.26 μg/L for DNBP, and 0.86 and 1.67 μg/L for DPHP. Abbreviations: Bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), and diphenyl phosphate (DPHP).