Case Report: High Prenatal Bisphenol A Exposure and Infant Neonatal Neurobehavior

Context: Most of the U.S. population is exposed to the high-production-volume chemical bisphenol A (BPA), but targetable sources of exposure remain to be determined. Animal studies and one human study suggest that BPA is a neurotoxicant

Response to the Letter by G. M. H. Swaen and R. Otter

Peer reviewedPostprin

Application of US EPA IRIS systematic review methods to the health effects of phthalates:Lessons learned and path forward

This special issue presents several systematic reviews of the potential human health effects associated with exposure to phthalates and addresses some of the considerations and challenges that were encountered over the course of performing these reviews. This editorial presents the views of the lead U.S. Environmental Protection Agency (EPA) researchers on the project and the Special Issue Editors with regard to lessons learned, implications of methods, and the path forward for systematic reviews to support human health assessment

Maternal exposure to childhood traumatic events, but not multi-domain psychosocial stressors, predict placental corticotrophin releasing hormone across pregnancy

Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur.publishedVersio

Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight

Human chorionic gonadotropin (hCG) is a placental hormone measured in pregnancy to predict individual level risk of fetal aneuploidy and other complications; yet may be useful in understanding placental origins of child development more generally. hCG was associated with maternal body mass index (BMI) and with birthweight. The primary aim here was to evaluate hCG as a mediator of maternal BMI effects on birthweight by causal mediation analysis. Subjects were 356 women from 3 U.S. sites (2010–2013). The 4-way decomposition method using med4way (STATA) was applied to screen for 5 types of effects of first trimester maternal BMI on birthweight: the total effect, the direct effect, mediation by hCG, additive interaction of BMI and hCG, and mediation in the presence of an additive interaction. Effect modification by fetal sex was evaluated, and a sensitivity analysis was performed to evaluate the assumption of unmeasured confounding. Additional placental-fetal biomarkers [pregnancy associated plasma protein A (PAPPA), second trimester hCG, inhibin-A, estriol, alpha fetoprotein] were analyzed for comparison. For first trimester hCG, there was a 0.20 standard deviation increase in birthweight at the 75th vs. 25th percentile of maternal BMI (95% CI 0.04, 0.36). Once stratified, the direct effect association was null in women carrying females. In women carrying males, hCG did not mediate the relationship. In women carrying females, there was a mediated effect of maternal BMI on birthweight by hCG in the reverse direction (−0.06, 95% CI: −0.12, 0.01), and a mediated interaction in the positive direction (0.06, 95% CI 0.00, 0.13). In women carrying males, the maternal BMI effect on birthweight was reverse mediated by PAPPA (−0.09, 95% CI: −0.17, 0.00). Sex-specific mediation was mostly present in the first trimester. Second trimester AFP was a positive mediator of maternal BMI effects in male infants only (0.06, 95% CI: −0.01, 0.13). Effect estimates were robust to potential bias due to unmeasured confounders. These findings motivate research to consider first trimester placental biomarkers and sex-specific mechanisms when quantifying the effects of maternal adiposity on fetal growth

Variability and Predictors of Urinary Bisphenol A Concentrations during Pregnancy

BackgroundPrenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy.ObjectiveOur goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy.MethodsWe measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models.ResultsGeometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations.ConclusionsThese results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures