Exposure to Synthetic Endocrine-Disrupting Chemicals in Relation to Maternal and Fetal Sex Steroid Hormones: A Scoping Review.

PURPOSE OF REVIEW: Many synthetic endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment and highly detected among pregnant people. These chemicals may disrupt maternal and/or fetal sex steroid hormones, which are critical to pregnancy maintenance and fetal development. Here, we review the epidemiological literature examining prenatal exposure to common synthetic EDCs in relation to maternal and fetal sex steroid hormones. RECENT FINDINGS: We performed a literature search using PubMed, SCOPUS, and Embase, ultimately identifying 29 articles for full review. Phenols, parabens, and persistent organic pollutants generally showed inverse associations with androgens, estrogens, and progesterone. Phthalates and per-and polyfluoroalkyl substances tended to be inversely associated with progesterone, while evidence regarding androgens and estrogens was mixed. Inconsistent, but noteworthy, differences by fetal sex and timing of exposure/outcome were observed. Overall, the literature suggests EDCs may disrupt maternal and fetal sex steroid activity, though findings are mixed. Given the pervasive, high-volume production of these synthetic chemicals and the critical functions sex steroid hormones play during gestation, additional research is warranted.

Advancing Understanding of Chemical Exposures and Maternal-child Health Through the U.S. Environmental Influences on Child Health Outcomes (ECHO) Program: A Scoping Review.

PURPOSE OF REVIEW: Environmental chemical exposures may disrupt child development, with long-lasting health impacts. To date, U.S. studies of early environmental exposures have been limited in size and diversity, hindering power and generalizability. With harmonized data from over 60,000 participants representing 69 pregnancy cohorts, the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program is the largest study of U.S. children's health. Here, we: (1) review ECHO-wide studies of chemical exposures and maternal-child health; and (2) outline opportunities for future research using ECHO data. RECENT FINDINGS: As of early 2024, in addition to over 200 single-cohort (or award) papers on chemical exposures supported by ECHO, ten collaborative multi-cohort papers have been made possible by ECHO data harmonization and new data collection. Multi-cohort papers have examined prenatal exposure to per- and polyfluoroalkyl substances (PFAS), phthalates, phenols and parabens, organophosphate esters (OPEs), metals, melamine and aromatic amines, and emerging contaminants. They have primarily focused on describing patterns of maternal exposure or examining associations with maternal and infant outcomes; fewer studies have examined later child outcomes (e.g., autism) although follow up of enrolled ECHO children continues. The NICHD's Data and Specimen Hub (DASH) database houses extensive ECHO data including over 470,000 chemical assay results and complementary data on priority outcome areas (pre, peri-, and postnatal, airway, obesity, neurodevelopment, and positive health), making it a rich resource for future analyses. ECHO's extensive data repository, including biomarkers of chemical exposures, can be used to advance our understanding of environmental influences on children's health. Although few published studies have capitalized on these unique harmonized data to date, many analyses are underway with data now widely available.

Associations between mycoestrogen exposure and sex steroid hormone concentrations in maternal serum and cord blood in the UPSIDE pregnancy cohort.

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17ß-estradiol (E2), they interact with estrogen receptors α/ß earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.

The role of prenatal maternal sex steroid hormones in weight and adiposity at birth and growth trajectories during infancy.

Objective: Intrauterine factors can impact fetal and child growth and may underlie the developmental origins of childhood obesity. Sex steroid hormone exposure during pregnancy is a plausible target because of the impact on placental vascularization, nutrient transportation, bone growth, adipogenesis, and epigenetic modifications. In this study we assessed maternal sex steroid hormones in each trimester in relation to birthweight, neonatal adiposity, and infant growth trajectories, and evaluate sensitive windows of development. Methods: Participants from a prospective pregnancy cohort who delivered at term were included in the analysis (n=252). Estrone, estradiol, and estriol, as well as total and free testosterone throughout gestation were assessed using high-performance liquid chromatography and tandem mass spectrometry. Path analyses were used to assess the direct associations of sex steroid hormones in each trimester with birth outcomes and infant growth trajectories (birth to 12 months) adjusting for covariates and considering moderation by sex. Results: The associations between prenatal sex steroid hormones and fetal/infant growth varied by sex and hormone assessment timing. First trimester estrone were associated with higher birthweight z-scores (ß=0.37, 95%CI: 0.02, 0.73) and truncal skinfold thickness (TST) at birth (ß=0.94, 95%CI: 0.34, 1.54) in female infants. Third trimester total testosterone was associated with higher TST at birth (ß=0.61, 95%CI: 0.02, 1.21) in male infants. First trimester estrone/estradiol and first and third trimesters testosterone were associated with lower probabilities of high stable weight trajectory compared to low stable weight trajectory (Estrone: ß=-3.87, 95%CI: -6.59, -1.16; First trimester testosterone: ß=-3.53, 95%CI: -6.63, -0.43; Third trimester testosterone: ß=-3.67, 95%CI: -6.66, -0.69) during infancy in male infants. Conclusions: We observed associations between prenatal sex steroid hormone exposure and birthweight, neonatal adiposity and infant growth that were sex and gestational timing dependent. Our findings suggest further investigation on additional mechanisms linking prenatal sex steroid exposure and fetal/postnatal growth is needed.

PFAS alters placental arterial vasculature in term human placentae: A prospective pregnancy cohort study.

INTRODUCTION: Perfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. OBJECTIVES: The objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. METHODS: Using data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. RESULTS: In both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (ß = -0.23, 95% CI: -0.41, -0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (ß = -0.19, 95% CI: -0.34, -0.051). There were no reliable differences in effect by fetal sex. DISCUSSION: The findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.

Risks of obstructive genitourinary birth defects in relation to trihalomethane and haloacetic acid exposures: expanding disinfection byproduct mixtures analyses using relative potency factors.

BACKGROUND: Some disinfection byproducts (DBPs) are teratogens based on toxicological evidence. Conventional use of predominant DBPs as proxies for complex mixtures may result in decreased ability to detect associations in epidemiological studies. OBJECTIVE: We assessed risks of obstructive genitourinary birth defects (OGDs) in relation to 12 DBP mixtures and 13 individual component DBPs. METHODS: We designed a nested registry-based case-control study (210 OGD cases; 2100 controls) in Massachusetts towns with complete quarterly 1999-2004 data on four trihalomethanes (THMs) and five haloacetic acids (HAAs). We estimated temporally-weighted average DBP exposures for the first trimester of pregnancy. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for OGD in relation to individual DBPs, unweighted mixtures, and weighted mixtures based on THM/HAA relative potency factors (RPF) from animal toxicology data for full-litter resorption, eye defects, and neural tube defects. RESULTS: We detected elevated aORs for OGDs for the highest of bromodichloromethane (aOR = 1.75; 95% CI: 1.15-2.65), dibromochloromethane (aOR = 1.71; 95% CI: 1.15-2.54), bromodichloroacetic acid (aOR = 1.56; 95%CI: 0.97-2.51), chlorodibromoacetic acid (aOR = 1.97, 95% CI: 1.23-3.15), and tribromoacetic acid (aOR = 1.90; 95%CI: 1.20-3.03). Across unweighted mixture sums, the highest aORs were for the sum of three brominated THMs (aOR = 1.74; 95% CI: 1.15-2.64), the sum of six brominated HAAs (aOR = 1.43; 95% CI: 0.89-2.31), and the sum of nine brominated DBPs (aOR = 1.80; 95% CI: 1.05-3.10). Comparing eight RPF-weighted to unweighted mixtures, the largest aOR differences were for two HAA metrics, which both were higher with RPF weighting; other metrics had reduced or minimally changed ORs in RPF-weighted models.

Connect: Cultivating Academic-Community Partnerships to Address Our Communities' Complex Needs During Public Health Crises.

BACKGROUND: Black and Latino communities have been disproportionately impacted by coronavirus disease 2019 and we sought to understand perceptions and attitudes in four heavily impacted New Jersey counties to develop and evaluate engagement strategies to enhance access to testing. OBJECTIVE: To establish a successful academic/community partnership team during a public health emergency by building upon longstanding relationships and using principles from community engaged research. METHODS: We present a case study illustrating multiple levels of engagement, showing how we successfully aligned expectations, developed a commitment of cooperation, and implemented a research study, with community-based and health care organizations at the center of community engagement and recruitment. LESSONS LEARNED: This paper describes successful approaches to relationship building including information sharing and feedback to foster reciprocity, diverse dissemination strategies to enhance engagement, and intergenerational interaction to ensure sustainability. CONCLUSIONS: This model demonstrates how academic/community partnerships can work together during public health emergencies to develop sustainable relationships.

Associations between neighborhood stress and maternal sex steroid hormones in pregnancy.

BACKGROUND: Neighborhood stressors (e.g., crime and deprivation) have been associated with adverse pregnancy outcomes including preterm birth and low birth weight. A potential mechanism is disruption of maternal endocrine pathways. While stress hormones (e.g., cortisol) have received much attention, other relevant hormones, including sex steroids, have been overlooked. METHODS: Pregnant women in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaires, and medical record data (n = 262). In each trimester, maternal serum total testosterone [TT], estrone, estradiol, and estriol were measured using LC/MS-MS and serum free testosterone was measured by equilibrium dialysis. In the third trimester, participants reported on neighborhood stress over the last year through the validated City Stress Inventory. We examined two subscales: 11-item neighborhood disorder (e.g., vacant buildings, crime) and 7-item exposure to violence (personal experiences of violence). Composite scores were calculated and examined categorically (quartile (Q) for neighborhood disorder and any/none for exposure to violence). We fitted linear mixed models examining associations between neighborhood stressors and sex steroid hormones across pregnancy as well as trimester-specific linear regression models, all adjusting for confounders. Secondarily, we stratified by fetal sex. Results are presented as percentage change (∆%) and 95% confidence interval (CI) in hormones. RESULTS: Most participants (73%) reported one or more exposures to neighborhood disorder; 22% reported any exposure to violence. In adjusted models, neighborhood disorder was associated with higher TT across pregnancy (Q2: %∆= 37.3, 95%CI: 13.2, 66.5; Q3: %∆= 22.2, 95%CI: 1.2, 47.5; and Q4: %∆= 25.7, 95%CI: 1.6, 55.3), with the strongest associations observed in the third trimester (Q2: %∆= 38.0, 95%CI: 10.6, 72.1; Q3: %∆= 29.2, 95%CI: 4.4, 59.9; and Q4: %∆=33.4, 95%CI: 4.9, 69.6). In stratified models, neighborhood disorder was associated with higher TT among women carrying male fetuses (%∆ range: 48.2-84.8). Exposure to violence was not associated with any hormones. CONCLUSION: Neighborhood disorder is associated with higher maternal testosterone levels, which may have implications for maternal and child health. Additional research is needed to understand the mechanisms by which neighborhood stress impacts endocrine physiology.

Per- and polyfluoroalkyl substances, gestational weight gain, postpartum weight retention and body composition in the UPSIDE cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals found in drinking water and consumer products, resulting in ubiquitous human exposure. PFAS have been linked to endocrine disruption and altered weight gain across the lifespan. A limited and inconsistent body of research suggests PFAS may impact gestational weight gain (GWG) and postpartum body mass index (BMI), which are important predictors of overall infant and maternal health, respectively. METHODS: In the Understanding Pregnancy Signals and Infant Development (UPSIDE/UPSIDE-MOMs) study (n = 243; Rochester, NY), we examined second trimester serum PFAS (PFOS: perfluorooctanesulfonic acid, PFOA: perfluorooctanoic acid, PFNA: perfluorononanoic acid, PFHxS: perfluorohexanesulfonic acid, PFDA: perfluorodecanoic acid) in relation to GWG (kg, and weekly rate of gain) and in the postpartum, weight retention (PPWR (kg) and total body fat percentage (measured by bioelectrical impedance)). We fit multivariable linear regression models examining these outcomes in relation to log-transformed PFAS in the whole cohort as well as stratified by maternal pre-pregnancy BMI (< 25 vs. = > 25 kg/m2), adjusting for demographics and lifestyle factors. We used weighted quantile sum regression to find the combined influence of the 5 PFAS on GWG, PPWR, and body fat percentage. RESULTS: PFOA and PFHxS were inversely associated with total GWG (PFOA: ß = -1.54 kg, 95%CI: -2.79, -0.30; rate ß = -0.05 kg/week, 95%CI: -0.09, -0.01; PFHxS: ß = -1.59 kg, 95%CI: -3.39, 0.21; rate ß = -0.05 kg/week, 95%CI: -0.11, 0.01) and PPWR at 6 and 12 months (PFOA 6 months: ß = -2.39 kg, 95%CI: -4.17, -0.61; 12 months: ß = -4.02 kg, 95%CI: -6.58, -1.46; PFHxS 6 months: ß = -2.94 kg, 95%CI: -5.52, -0.35; 12 months: ß = -5.13 kg, 95%CI: -8.34, -1.93). PFOA was additionally associated with lower body fat percentage at 6 and 12 months (ß = -1.75, 95%CI: -3.17, -0.32; ß = -1.64, 95%CI: -3.43, 0.16, respectively) with stronger associations observed in participants with higher pre-pregnancy BMI. The PFAS mixture was inversely associated with weight retention at 12 months (ß = -2.030, 95%CI: -3.486, -0.573) amongst all participants. CONCLUSION: PFAS, in particular PFOA and PFHxS, in pregnancy are associated with altered patterns of GWG and postpartum adiposity with potential implications for fetal development and long-term maternal cardiometabolic health.

Optimized extraction and analysis methods using liquid chromatography-tandem mass spectrometry for zearalenone and metabolites in human placental tissue.

Zearalenone and its metabolites, a group of endocrine disrupting mycotoxins, have been linked to adverse reproductive health effects. They cross the placental barrier, potentially reaching the fetus. In this study, we adapted and optimized our protocol previously used for urine, to measure these mycotoxins in human placentas. We combined a supported liquid extraction step using Chem Elut cartridges with solid phase extraction on Discovery® DSC-NH2 tubes. The optimized extraction efficiencies were between 68 and 80% for all metabolites. Analysis was performed by UHPLC-HRMS using a Betasil™ Phenyl-Hexyl column eluted with a gradient of acetonitrile-methanol-water. The chromatography method separated all analytes in under 15 min. Validation experiments confirmed the method's sensitivity, with LODs ranging from 0.0055 to 0.011 pg/mg tissue. The method was linear over a range of 0.0025-1.5 pg/mg tissue with R2 values ≥ 0.994. Precision and accuracy calculations ranged from 4.7-7.9% and 0.6-6.7% respectively. The method was then successfully applied to a subset of placenta samples (n = 25) collected from an ongoing prospective birth cohort. Interestingly, 92% of the samples contained at least one measurable zearalenone metabolite, providing initial indication of potentially widespread exposure during pregnancy.

Assessment of personal care product use and perceptions of use in a sample of US adults affiliated with a university in the Northeast.

Evidence supports unequal burdens of chemical exposures from personal care products (PCPs) among some groups, namely femme-identifying and racial and ethnic minorities. In this study, we implemented an online questionnaire to assess PCP purchasing and usage behaviors and perceptions of use among a sample of US adults recruited at a Northeastern university. We collected PCP use across seven product categories (hair, beauty, skincare, perfumes/colognes, feminine hygiene, oral care, other), and behaviors, attitudes, and perceptions of use and safety across sociodemographic factors to evaluate relationships between sociodemographic factors and the total number of products used within the prior 24-48 h using multivariable models. We also summarized participants' perceptions and attitudes. Among 591 adults (20.0% Asian American/Pacific Islander [AAPI], 5.9% Hispanic, 9.6% non-Hispanic Black [NHB], 54.6% non-Hispanic White [NHW], and 9.9% multiracial or other), the average number of PCPs used within the prior 24-48 h was 15.6 ± 7.7. PCP use was greater among females than males (19.0 vs. 7.9, P < 0.01) and varied by race and ethnicity among females. Relative to NHWs, AAPI females used fewer hair products (2.5 vs. 3.1) and more feminine hygiene products (1.5 vs. 1.1), NHB females used more hair products (3.8 vs. 3.1), perfumes (1.0 vs. 0.6), oral care (2.3 vs. 1.9), and feminine hygiene products (1.8 vs. 1.1), and multiracial or other females used more oral care (2.2 vs. 1.9) and feminine hygiene products (1.5 vs. 1.1) (P-values <0.05). Generally, study participants reported moderate concern about exposures and health effects from using PCPs, with few differences by gender, race, and ethnicity. These findings add to the extant literature on PCP use across sociodemographic characteristics. Improving the understanding of patterns of use for specific products and their chemical ingredients is critical for developing interventions to reduce these exposures, especially in vulnerable groups with an unequal burden of exposure.

A comparison of four liquid chromatography-mass spectrometry platforms for the analysis of zeranols in urine.

Targeted biomonitoring studies quantifying the concentration of zeranols in biological matrices have focused on liquid chromatography interfaced to mass spectrometry (LC-MS). The MS platform for measurement, quadrupole, time-of-flight (ToF), ion trap, etc., is often chosen based on either sensitivity or selectivity. An instrument performance comparison of the benefits and limitations using matrix-matched standards containing 6 zeranols on 4 MS instruments, 2 low-resolution (linear ion traps), and 2 high-resolution (Orbitrap and ToF) was undertaken to identify the best measurement platform for multiple biomonitoring projects characterizing the endocrine disruptive properties of zeranols. Analytical figures of merit were calculated for each analyte to compare instrument performance across platforms. The calibration curves had correlation coefficients r = 0.989 ± 0.012 for all analytes and LODs and LOQs were ranked for sensitivity: Orbitrap > LTQ > LTQXL > G1 (V mode) > G1 (W mode). The Orbitrap had the smallest measured variation (lowest %CV), while the G1 had the highest. Instrumental selectivity was calculated using full width at half maximum (FWHM) and as expected, the low-resolution instruments had the broadest spectrometric peaks, concealing coeluting peaks under the same mass window as the analyte. Multiple peaks from concomitant ions, unresolved at low resolution (within a unit mass window), were present but did not match the exact mass predicted for the analyte. For example, the high-resolution platforms were able to differentiate between a concomitant peak at 319.1915 from the analyte at 319.1551, included in low-resolution quantitative analyses demonstrating the need to consider coeluting interfering ions in biomonitoring studies. Finally, a validated method using the Orbitrap was applied to human urine samples from a pilot cohort study.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Prenatal Cadmium Exposure and Maternal Sex Steroid Hormone Concentrations across Pregnancy.

Cadmium exposure has been associated with adverse perinatal outcomes. One possible mechanism is endocrine disruption. Studies of non-pregnant adults suggest that cadmium impacts androgen production; here, we examined these associations during pregnancy. Participants in the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort provided biospecimens and questionnaire data in each trimester (n = 272). We quantified urinary cadmium, serum total testosterone (TT), estrone, estradiol, and estriol and serum free testosterone (fT). In adjusted longitudinal models, we examined sex steroid concentrations across pregnancy in relation to specific gravity-adjusted, ln-transformed cadmium concentrations. Additionally, we examined trimester-specific associations and stratified models by fetal sex. Results are presented as percent change (%∆) in hormone concentrations. In longitudinal models, higher cadmium concentrations were associated with lower fT across pregnancy (%∆ = -5.19, 95%CI: -8.33, -1.93), with no differences in other hormones observed. In trimester-specific models, higher cadmium concentrations were associated with lower TT in trimester 2 (%∆ = -15.26, 95%CI: -25.15, -4.06) and lower fT in trimester 3 (%∆ = -14.35, 95%CI: -19.75, -8.59). Associations with TT were stronger in pregnancies carrying female fetuses. Maternal cadmium exposure may be associated with reduced testosterone in pregnancy. Additional work is necessary to understand how alterations in gestational testosterone activity may impact pregnancy and child health.

Protective role of the placental efflux transporter BCRP/ABCG2 in the relationship between prenatal cadmium exposure, placenta weight, and size at birth.

BACKGROUND AND AIM: Placental efflux transporter proteins, such as BCRP, reduce the placental and fetal toxicity of environmental contaminants but have received little attention in perinatal environmental epidemiology. Here, we evaluate the potential protective role of BCRP following prenatal exposure to cadmium, a metal that preferentially accumulates in the placenta and adversely impacts fetal growth. We hypothesized that individuals with a reduced function polymorphism in ABCG2, the gene encoding BCRP, would be most vulnerable to the adverse impacts of prenatal cadmium exposure, notably, smaller placental and fetal size. METHODS: We measured cadmium in maternal urine samples at each trimester and in term placentas from UPSIDE-ECHO study participants (NY, USA; n = 269). We fit adjusted multivariable linear regression and generalized estimating equation models to examine log-transformed urinary and placental cadmium concentrations in relation to birthweight, birth length, placental weight, and fetoplacental weight ratio (FPR) and stratified models by ABCG2 Q141K (C421A) genotype. RESULTS: Overall 17% of participants expressed the reduced-function ABCG2 C421A variant (AA or AC). Placental cadmium concentrations were inversely associated with placental weight (ß = -19.55; 95%CI: -37.06, -2.04) and trended towards higher FPR (ß = 0.25; 95%CI: -0.01, 0.52) with stronger associations in 421A variant infants. Notably, higher placental cadmium concentrations in 421A variant infants were associated with reduced placental weight (ß = -49.42; 95%CI: 98.87, 0.03), and higher FPR (ß = 0.85, 95%CI: 0.18, 1.52), while higher urinary cadmium concentration was associated with longer birth length (ß = 0.98; 95%CI: 0.37, 1.59), lower ponderal index (ß = -0.09; 95%CI: 0.15, -0.03), and higher FPR (ß = 0.42; 95%CI: 0.14, 0.71). CONCLUSIONS: Infants with reduced function ABCG2 polymorphisms may be particularly vulnerable to the developmental toxicity of cadmium as well as other xenobiotics that are BCRP substrates. Additional work examining the influence of placental transporters in environmental epidemiology cohorts is warranted.

Prenatal perfluoroalkyl substances exposure and maternal sex steroid hormones across pregnancy.

BACKGROUND: Poly- and perfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants that may act as endocrine disruptors in utero, but the specific endocrine pathways are unknown. OBJECTIVE: We examined associations between maternal serum PFAS and sex steroid hormones at three time points during pregnancy. METHODS: Pregnant women participating in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaire, and medical record data in each trimester (n = 285). PFAS (including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA)) were analyzed in second-trimester serum samples by high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Total testosterone [TT], free testosterone [fT], estrone [E1], estradiol [E2], and estriol [E3]) were measured by LC-MS/MS in serum samples from each trimester. Linear mixed models with random intercepts were used to examine associations between log-transformed PFAS concentrations and hormone levels, adjusting for covariates, and stratifying by fetal sex. Results are presented as the mean percentage difference (Δ%) in hormone levels per ln-unit increase in PFAS concentration. RESULTS: In adjusted models, PFHxS was associated with higher TT (%Δ = 20.0, 95%CI: 1.7, 41.6), particularly among women carrying male fetuses (%Δ = 15.3, 95%CI: 1.2, 30.7); this association strengthened as the pregnancy progressed. PFNA (%Δ = 7.9, 95%CI: 3.4, 12.5) and PFDA (%Δ = 7.2, 95%CI: 4.9, 9.7) were associated with higher fT, with associations again observed only in women carrying male fetuses. PFHxS was associated with higher levels of E2 and E3 in women carrying female fetuses (%Δ = 13.2, 95%CI: 0.5, 29.1; %Δ = 17.9, 95%CI: 3.2, 34.8, respectively). No associations were observed for PFOS and PFOA. CONCLUSION: PFHxS, PFNA, and PFDA may disrupt androgenic and estrogenic pathways in pregnancy in a sex-dependent manner.

Community- Versus Health Care Organization-Based Approaches to Expanding At-Home COVID-19 Testing in Black and Latino Communities, New Jersey, 2021.

At-home COVID-19 testing offers convenience and safety advantages. We evaluated at-home testing in Black and Latino communities through an intervention comparing community-based organization (CBO) and health care organization (HCO) outreach. From May through December 2021, 1100 participants were recruited, 94% through CBOs. The odds of COVID-19 test requests and completions were significantly higher in the HCO arm. The results showed disparities in test requests and completions related to age, race, language, insurance, comorbidities, and pandemic-related challenges. Despite the popularity of at-home testing, barriers exist in underresourced communities. (Am J Public Health. 2022;112(S9):S918-S922. https://doi.org/10.2105/AJPH.2022.306989).

Phenols, Parabens, Phthalates and Puberty: a Systematic Review of Synthetic Chemicals Commonly Found in Personal Care Products and Girls' Pubertal Development.

PURPOSE OF REVIEW: Exposure to endocrine disrupting chemicals through personal care products (PCPs) is widespread and may disrupt hormone-sensitive endpoints, such as timing of puberty. Given the well-documented (and ongoing) decline in age at menarche in many populations, we conducted a systematic review of the epidemiological literature on exposure to chemicals commonly found in PCPs (including certain phthalates, phenols, and parabens) in relation to girls' pubertal development. RECENT FINDINGS: The preponderance of research on this topic has examined phthalate exposures with the strongest evidence indicating that prenatal monoethyl phthalate (MEP) concentrations may be associated with slightly earlier timing of puberty, including age at menarche. Findings examining peri-pubertal phthalate exposures and pubertal outcomes were less consistent as were studies of prenatal and peri-pubertal phenol exposures. Very few studies had examined parabens in relation to girls' pubertal development. Common study limitations included potential exposure misclassification related to use of spot samples and/or mistimed biomarker assessment with respect to the outcomes. The role of body size as a mediator in these relationships remains unresolved. Overall, evidence of associations between chemical exposures in PCPs and girls' pubertal development was conflicting. When associations were observed, effect sizes were small. Nevertheless, given the many environmental, social, and behavioral factors in the modern environment that may act synergistically to accelerate timing of puberty, even marginal changes may be cause for concern, with implications for cancer risk, mental health, and cardiometabolic disease in later life.

Phthalate Exposures and Placental Health in Animal Models and Humans: A Systematic Review.

Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied. Most recently, there has been interest in the impacts of phthalates on the placenta, a transient major endocrine organ critical to maintenance of the uterine environment and fetal development. Phthalate-induced changes in placental structure and function may have significant impacts on the course of pregnancy and ultimately, child health. Prior reviews have described the literature on phthalates and placental health; however to date, there has been no comprehensive, systematic review on this topic. Here, we review 35 papers (24 human and 11 animal studies) and summarize phthalate exposures in relation to an extensive set of placental measures. Phthalate-related alterations were reported for placental morphology, hormone production, vascularization, histopathology, and gene/protein expression. The most consistent changes were observed in vascular and morphologic endpoints, including cell composition. These changes have implications for pregnancy complications such as preterm birth and intrauterine growth restriction as well as potential ramifications for children's health. This comprehensive review of the literature, including common sources of bias, will inform the future work in this rapidly expanding field.