Session: OR42-Pregnancy-Related Reproductive Endocrinology
Room 11 (San Diego Convention Center)
Outstanding Abstract Award
Methods. Subjects were enrolled in multicenter prospective pregnancy cohort. Phthalates and hCG were measured in urine and serum samples, respectively, collected in the first trimester (N=362). Neonatal exams were performed by trained study staff. Multivariate linear regression was used to estimate sex-specific associations of the placental hormones with AGD (males: AS: anus to scrotum, AP: anus to penis; females AF: anus to fourchette; AC: anus to clitoris), birthweight for gestational age z-score, and 5 urinary phthalate concentrations including MnBP, mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), monoethylhexyl phthalate (MEHP), and monoethyl phthalate (MEP). To combine data across centers, we generated z-scores of the analyte values. We applied causal inference methods to estimate the total effect of phthalates and hCG on AGD, and compared it to the controlled direct effect (CDE) of the phthalates after removing the hCG effect.
Results. Higher hCG was associated with lower AGD-AS in males (-0.64 mm per 1 unit increase in the hCG z-score, standard error (SE) 0.31) but not females (interaction of hCG by fetal sex p=0.03). Higher MnBP and MBzP were associated with higher hCG expression in female fetuses and lower expression in males (interaction p-value=0.01). AGD-AP and AGD-AC were not correlated with first trimester placental hormones. In Aim 2, for every log unit increase in urinary MEHP and MnBP, male AGD decreased by 1.2 mm. If we administered a hypothetical substance that completely blocked the effect of hCG, then MEHP and MnBP would induce only a 0.87 mm and 0.99 mm decrease in AGD respectively.
Conclusion. The early placenta is a site of endocrine disruption, and a contributor to the development of the fetal genitalia. hCG may partially mediate the effects of phthalates on fetal genitalia. By monitoring of first trimester hCG, normalized by fetal sex, we may have the opportunity to identify abnormal development, intervene and improve the health of the child.
Nothing to Disclose: JJA, MKL, NIA, EB, RN, SS, MPT, SJJ, LB, JBR, SHS
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