Faculty Bibliography

The association between prenatal phthalate exposure and late preterm birth (LPTB) is unclear. We examined singleton pregnancies (2006"“2011) from a racially and socioeconomically diverse sample of women in the CANDLE cohort of the ECHO-PATHWAYS Consortium. Urine collected in the second and third trimester was analyzed for 14 phthalate metabolites. Multivariate logistic and linear regressions were performed for LPTB, defined as delivery 34"“37 weeks, and gestational week, respectively. Models were controlled for socio-demographics, behavioral factors, clinical measurements, medical history, and phthalates in the other trimester. Effect modification by race and pregnancy stress, indicated by intimate partner violence (IPV), was investigated. We conducted a secondary analysis in women with spontaneous preterm labor. The rate of LPTB among 1408 women (61% Black, 32% White) was 6.7%. There was no evidence of decreased gestational age (GA) in association with any phthalate metabolite. Each two-fold increase in third trimester mono-benzyl phthalate (MBzP) was associated with 0.08 weeks longer gestational age (95% CI: 0.03, 0.12). When restricting to women with spontaneous labor, second trimester mono-n-butyl phthalate (MBP) was associated with 54% higher odds (95% CI: 2%, 132%) of LPTB. Associations were not modified by maternal race or IPV exposure. In conclusion, we observed mixed evidence concerning our hypothesis that prenatal phthalate exposure increases risk of LPTB, though secondary analyses suggest increased risk of spontaneous LPTB associated with MBP, which is consistent with a recent pooled analysis of 16 cohorts.

Despite high production and usage, little is known about exposure to bisphenol diglycidyl ethers (BDGEs) and their derivatives in pregnant women and fetuses. In this study, we determined nine BDGEs in 106 paired maternal and cord serum samples collected from e-waste dismantling sites in South of China. Bisphenol A bis (2,3-dihydroxypropyl) glycidyl ether (BADGE·2H₂O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H₂O), and bisphenol F diglycidyl ether (BFDGE) were the major BDGEs, with median concentrations of 0.57, 4.07, and 1.60 ng/mL, respectively, in maternal serum, and of 3.58, 5.61, and 0.61 ng/mL, respectively, in cord serum. The transplacental transfer efficiencies (TTEs) were estimated for BDGEs found in samples, and median values were in the range of 0.98 (BFDGE) to 5.91 (BADGE·2H₂O). Our results suggested that passive diffusion plays a role in the placental transfer of BADGE·HCl·H₂O and BFDGE, whereas several mechanisms contribute to the high accumulation of BADGE·2H₂O in cord serum. Multiple linear regression analysis indicated significant associations between maternal serum concentrations of BDGEs and blood clinical biomarkers, especially those related to liver injuries, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and adenosine deaminase (ADA) (P < 0.05). To our knowledge, this is the first study to report the occurrence of BDGEs in paired maternal-fetal serum samples and provide new insights into prenatal and fetal exposures. The newly discovered TTEs in maternal-fetal pairs contribute to a fuller inventory of the transmission activity of pollutants in the human body, ultimately adding to a more significant comprehensive risk evaluation.

This paper describes a methodology for simultaneous determination of 19 steroid hormones, viz. estrone, estradiol, estriol, testosterone, 5α-dihydrotestosterone, androstenedione, androstenediol, dehydroepiandrosterone, progesterone, pregnenolone, 17α-OH-progesterone, 17α-OH-pregnenolone, cortisone, cortisol, 11-deoxycortisol, 11-deoxycorticosterone, 11-dehydrocorticosterone, aldosterone, and corticosterone, in 500-µL of urine or serum/plasma. The method was optimized using isotopically labeled internal standards and liquid-liquid extraction followed by detection using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS). Dansylation of estrogens significantly improved their sensitivities (~11- to 23-fold) and chromatographic separation. The respective limit of detection (LOD) and limit of quantification (LOQ) of all analytes were 0.04-0.28 and 0.14-0.92 ng/mL in human urine, and 0.11-0.35 and 0.38-1.18 ng/mL in human serum/plasma. Recoveries of all analytes (except for progesterone) fortified at 10, 20, and 200 ng/mL in urine and serum were 80-120%, with standard deviations ranging from 0 to 17.3%. Repeated analysis of similarly fortified urine and serum samples yielded intra-day and inter-day variations of 0-21.7% and 0.16-11.5%, respectively. All analytes except cortisone exhibited weak matrix effects in urine and serum (-13.9-18.2%). The method was further validated through the analysis of the National Institute of Standards and Technology (NIST) plasma Standard Reference Material (SRM1950) with certified concentrations for cortisol, progesterone, and testosterone (coefficient of variation: 3-11%). The developed method was applied in the analysis of urine samples from 20 volunteers, which revealed the occurrence of 16 analytes with detection frequencies (DFs) &gt; 80%. Furthermore, 15 analytes were found in plasma SRM1950, indicating the feasibility of our method in the analysis of steroid hormones in urine and serum/plasma. This method will facilitate analysis of steroid hormones in population-based biomonitoring studies.

BACKGROUND:Epidemiological study findings are inconsistent regarding associations between prenatal polycyclic aromatic hydrocarbon (PAH) exposures and childhood behavior. This study examined associations of prenatal PAH exposure with behavior at age 4-6 years in a large, diverse, multi-region prospective cohort. Secondary aims included examination of PAH mixtures and effect modification by child sex, breastfeeding, and child neighborhood opportunity. METHODS:The ECHO PATHWAYS Consortium pooled 1118 mother-child dyads from three prospective pregnancy cohorts in six U.S. cities. Seven PAH metabolites were measured in prenatal urine. Child behavior was assessed at age 4-6 using the Total Problems score from the Child Behavior Checklist (CBCL). Neighborhood opportunity was assessed using the socioeconomic and educational scales of the Child Opportunity Index. Multivariable linear regression was used to estimate associations per 2-fold increase in each PAH metabolite, adjusted for demographic, prenatal, and maternal factors and using interaction terms for effect modifiers. Associations with PAH mixtures were estimated using Weighted Quantile Sum Regression (WQSR). RESULTS:The sample was racially and sociodemographically diverse (38% Black, 49% White, 7% Other; household-adjusted income range $2651-$221,102). In fully adjusted models, each 2-fold increase in 2-hydroxynaphthalene was associated with a lower Total Problems score, contrary to hypotheses (b = -0.80, 95% CI = -1.51, -0.08). Associations were notable in boys (b = -1.10, 95% CI = -2.11, -0.08) and among children breastfed 6+ months (b = -1.31, 95% CI = -2.25, -0.37), although there was no statistically significant evidence for interaction by child sex, breastfeeding, or neighborhood child opportunity. Associations were null for other PAH metabolites; there was no evidence of associations with PAH mixtures from WQSR. CONCLUSION/CONCLUSIONS:In this large, well-characterized, prospective study of mother-child pairs, prenatal PAH exposure was not associated with adverse child behavior scores. Future studies characterizing the magnitude of prenatal PAH exposure and studies in older childhood are needed.

Volatile organic compounds (VOCs) are ubiquitous environmental pollutants, exposure to which is associated with birth defects, neurocognitive and reproductive impairments, and cancer. Little is known, however, about VOC exposure in pet dogs and cats, which represent sentinels for human exposure as well as having value as companion animals. In this study, we determined 38 VOC metabolites (VOCMs) in urine samples collected from 47 dogs and 42 cats from the Albany area of New York State. Seventeen (in cats) to twenty (in dogs) VOCMs were found at detection frequencies (DFs) above 60%. The creatinine-adjusted geometric mean (GM) concentrations of individual VOCMs ranged from 5.43 (EMA) to 761 μg/g (3HPMA) in dog urine and 0.824 (SBMA) to 278 μg/g (ATCA) in cat urine. The ∑20 VOCM concentration in dog urine was 2280 μg/g (geometric mean) and the ∑17 VOCM concentration in cat urine was 847 μg/g. Eight individual VOCMs were significantly more abundant in dog than in cat urine, and the urinary concentrations of several VOCMs in dogs were comparable to those reported for human tobacco smokers. Metabolites of acrolein accounted for 43% of ∑20 VOCM concentration in dogs, whereas those of cyanide and benzene accounted for 60% of ∑17 VOCM concentration in cats. Based on acrylamide exposure doses, calculated hazard quotients were above 1 in 77% of dogs and 50% of cats studied, and cancer risk values (using a benchmark of 10^-6) from exposure to acrylamide exceeded 1 for all dogs and cats. This is the first study to report VOCM concentrations in urine collected from pet dogs and cats and highlights the need to identify sources and health implications of VOCs exposure in these animals.

BACKGROUND:Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. OBJECTIVES/OBJECTIVE:We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. METHODS:We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. RESULTS:Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability. DISCUSSION/CONCLUSIONS:Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

Legacy [e.g., brominated- (BFRs)] and alternative [e.g., organophosphate- (OPFRs) and nitrogenous- (NFRs)] flame retardants have a propensity to migrate out of consumer products, and thus are dispersed in indoor microenvironments. In this study, simultaneous presence of 11 BFRs, 18 OPFRs and 11 NFRs were measured in house dust collected from Tianjin, China. OPFRs were found at the highest concentrations, with a median value of 3200 ng/g, followed by NFRs (2600) and BFRs (1600). Tris(2-butoxyethyl) phosphate (median: 1800 ng/g), melamine (1100), and BDE-209 (870) were the top three most abundant chemicals in the respective groups. Location-specific patterns of flame retardant concentrations were found with 30%, 20% and 10% of samples were predominated by OPFRs, NFRs and BFRs, respectively, and the remaining samples contained by two or more of the chemical groups occurring concurrently. Network and cluster analysis results indicated the existence of multiple sources of flame retardants in the indoor microenvironment. Estimated human daily intakes via indoor dust ingestion were approximately several tens of ng/kg bw/day and were below their respective reference dose values. Our results indicate widespread occurrence of multiple flame retardant families in indoor dust and suggest need for continued monitoring and efforts to reduce exposures through dust ingestion.

BACKGROUND:African Americans (AAs) experience high rates of adverse pregnancy outcomes relative to Whites. Differential in utero exposure to environmental chemicals and psychosocial stressors may explain some of the observed health disparities, as exposures to per- and polyfluoroalkyl substances (PFAS) and experiences of discrimination have been linked to adverse birth outcomes. Few studies have examined chemicals and non-chemical stressors together as an exposure mixture, which may better reflect real-life exposure patterns. Here, we adapted methods designed for the analysis of exposure mixtures to examine joint effects of PFAS and psychosocial stress on birth outcomes among AAs. METHODS:348 participants from the Atlanta African American Maternal-Child cohort were included in this study. Four PFAS were measured in first trimester serum samples. Self-report questionnaires were administered during the first trimester and were used to assess psychosocial stress (perceived stress, depression, anxiety, gendered racial stress). Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to estimate the joint effects between PFAS and psychosocial stressors on gestational age at delivery and birthweight for gestational age z-scores. All models were adjusted for maternal education, maternal age, parity, and any alcohol, tobacco and marijuana use. RESULTS:Our analytic sample included a socioeconomically diverse group of pregnant women, with 79 % receiving public health insurance. In quantile g-computation models, a simultaneous one-quartile increase in all PFAS, perceived stress, depression, anxiety, and gendered racial stress was associated with a reduction in birthweight z-scores (mean %change per quartile increase = -0.24, 95 % confidence interval = -0.43, -0.06). BKMR similarly showed that increasing all exposures in the mixture was associated with a modest decrease in birthweight z-scores, but not a reduced length of gestation. DISCUSSION/CONCLUSIONS:Using methods designed for analyzing exposure mixtures, we found that a simultaneous increase in in utero PFAS and psychosocial stressors was associated with reduced birthweight for gestational age z-scores.

Importance/UNASSIGNED:Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. Objective/UNASSIGNED:To evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption. Design, Setting, and Participants/UNASSIGNED:The Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022. Exposures/UNASSIGNED:Concentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP. Main Outcomes and Measures/UNASSIGNED:Child z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated. Results/UNASSIGNED:In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (β = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (β = -0.27; 95% CI, -0.47 to -0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (β = -0.16 [95% CI, -0.31 to -0.01] at 4 years; β = -0.37 [95% CI, -0.57 to -0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (β = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Conclusions and Relevance/UNASSIGNED:Intrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

BACKGROUND/UNASSIGNED:fetal growth trajectories and assessed whether maternal stress modified these associations. METHODS/UNASSIGNED:= 833 scans, GA range 10-42 weeks, mean 2.4 scans/participant). Adjusted linear mixed models with a GA quadratic growth curve were used for each PFAS exposure and growth outcome. PFOS and PFHxS were modeled continuously (100% sample detection), while PFOA, PFNA, and PFDA were modeled categorically (57-70% sample detection). Scores on the Perceived Stress Scale (PSS) measured in pregnancy were dichotomized at the median (<13 vs. ≥ 13) in stratified models. RESULTS/UNASSIGNED:= -0.8, 95% CI -1.6, -1.1). CONCLUSIONS/UNASSIGNED:Prenatal PFOA exposure adversely impacted fetal head biometric parameters in participants experiencing higher stress during pregnancy.