Faculty Bibliography

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. METHODS:In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). RESULTS:PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. CONCLUSIONS:Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.

Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

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:), 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.

BACKGROUND:Fetal exposure to bisphenols and phthalates may lead to alterations in the respiratory and immune system development in children, and to adverse respiratory health. AIM/OBJECTIVE:To study the associations of fetal bisphenols and phthalates exposure with lung function and asthma at age 13 years. STUDY DESIGN AND METHODS/METHODS:This study among 1020 children was embedded in a population-based prospective cohort study. We measured maternal urine bisphenol and phthalate concentrations in the first, second and third trimester of pregnancy, and lung function by spirometry and asthma by questionnaires at age 13 years. Multivariable linear and logistic regression models were applied. RESULTS:in boys and girls, and of higher first trimester bisphenol S with a decreased risk of asthma in boys and an increased risk of asthma in girls, these results did not remain significant after correction for multiple testing. Results were not modified by maternal history of asthma or atopy. CONCLUSIONS:Maternal urine bisphenol and phthalate concentrations averaged or in specific trimesters during pregnancy were not strongly associated with childhood lung function and asthma at age 13 years. BPS, as a BPA substitute, tended to be associated with impaired lung function and altered risk of asthma, partly sex-dependent, but its strength was limited by a relatively low detection rate and should be queried in contemporary cohorts.

BACKGROUND AND OBJECTIVES:Infant weight patterns predict subsequent weight outcomes. Rapid infant weight gain, defined as a >0.67 increase in weight-for-age z-score (WAZ) between two time points in infancy, increases obesity risk. Higher oxidative stress, an imbalance between antioxidants and reactive oxygen species, has been associated with low birthweight and paradoxically also with later obesity. We hypothesized that prenatal oxidative stress may also be associated with rapid infant weight gain, an early weight pattern associated with future obesity. METHODS:Within the NYU Children's Health and Environment Study prospective pregnancy cohort, we analyzed associations between prenatal lipid, protein, and DNA urinary oxidative stress biomarkers and infant weight data. Primary outcome was rapid infant weight gain (>0.67 increase in WAZ) between birth and later infancy at the 8 or 12 month visit. Secondary outcomes included: very rapid weight gain (>1.34 increase in WAZ), low (<2500 g) or high (≥4000 g) birthweight, and low (< -1 WAZ) or high (>1 WAZ) 12 month weight. RESULTS:Pregnant participants consented to the postnatal study (n = 541); 425 participants had weight data both at birth and in later infancy. In an adjusted binary model, prenatal 8-iso-PGF2α, a lipid oxidative stress biomarker, was associated with rapid infant weight gain (aOR 1.44; 95% CI: 1.16, 1.78, p = 0.001). In a multinomial model using ≤0.67 change in WAZ as a reference group, 8-iso-PGF2α was associated with rapid infant weight gain (defined as >0.67 but ≤1.34 WAZ; aOR 1.57, 95% CI: 1.19, 2.05, p = 0.001) and very rapid infant weight gain (defined as >1.34 WAZ; aOR 1.33; 95% CI: 1.02, 1.72, p < 0.05) Secondary analyses detected associations between 8-iso-PGF2α and low birthweight outcomes. CONCLUSIONS:We found an association between 8-iso-PGF2α, a lipid prenatal oxidative stress biomarker, and rapid infant weight gain, expanding our understanding of the developmental origins of obesity and cardiometabolic disease.

1,3-Diphenylguanidine (DPG), 1,3-di-o-tolylguanidine (DTG), and 1,2,3-triphenylguanidine (TPG) are rubber additives widely present in the indoor environment. Nevertheless, little is known about their human exposure. We developed a method for the quantification of DPG, DTG, and TPG in human urine, using high-performance liquid chromatography-tandem mass spectrometry. The quantitative analysis of target analytes at parts-per-trillion levels in urine was optimized using hydrophilic-lipophilic balanced solid-phase extraction and isotopic dilution. The method limits of detection and quantification were in the range of 0.002-0.02 and 0.005-0.05 ng/mL, respectively. The recoveries of all analytes in human urine fortified at 1, 5, 10, and 20 ng/mL concentrations were in the range of 75.3-111%, with standard deviations of 0.7-4%. The repeated measurement of similarly fortified human urine yielded intra-day and inter-day variations of 0.47-3.90 and 0.66-3.76%, respectively. The validated method was applied in the measurement of DPG, DTG, and TPG in real human urine samples, which revealed the occurrence of DPG in children's urine samples (n = 15) with a detection frequency of 73% and at a median concentration of 0.05 ng/mL. DPG was found in 20% of adults' urine samples (n = 20).

BACKGROUND:Epidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure. OBJECTIVE:We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. METHODS:We included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ. RESULTS: = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (β = -1.14 [95%CI:-2.00,-0.28]). SIGNIFICANCE/CONCLUSIONS:In this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.

Occurrence of volatile organic compounds (VOCs) such as benzene in personal care products is a topic of public health concern. Sunscreen products are extensively used to protect skin and hair from UV radiation from sun light. Nevertheless, little is known about exposure doses and risks of VOCs present in sunscreens. In this study, we determined the concentrations of and exposure to three VOCs, namely benzene, toluene and styrene, in 50 sunscreen products marketed in the United States. Benzene, toluene and styrene were found in 80 %, 92 % and 58 %, respectively, of the samples analyzed at mean concentrations of 45.8 ng/g (range: 0.007-862), 89.0 ng/g (range: 0.006-470) and 161 ng/g (range: 0.006-1650), respectively. The mean dermal exposure doses (DEDs) to benzene, toluene and styrene of children/teenagers were 68.3, 133 and 441 ng/kg-bw/d, respectively, whereas those of adults were 48.7, 94.6 and 171 ng/kg-bw/d, respectively. The lifetime cancer risk from benzene concentrations present in 22 sunscreen products (44 % of the samples) for children/teenagers and 19 sunscreen products (38 %) for adults, exceeded the acceptable benchmark risk level (1.0 × 10^-6). This is the first study to comprehensively assess the concentrations of and risks to benzene, toluene and styrene present in sunscreen products.

1,3-Diphenylguanidine (DPG), benzothiazole (BTH), benzotriazole (BTR), and their derivatives are high-production-volume chemicals widely used in tires, corrosion inhibitors and plastic products. Vehicular traffic is an important source of these chemicals in the environment. Despite this, little is known about the occurrence of these chemicals in roadside soils. In this study, we determined the concentrations, profiles, and distribution patterns of 3 DPGs, 5 BTHs, and 7 BTRs in 110 soil samples collected from northeastern United States. We found widespread occurrence of 12 out of the 15 analytes measured in roadside soils, at detection frequencies ≥71 % and median concentrations in the range of 0.38-380 ng/g (dry weight). DPGs were the predominant chemicals accounting for 63 % of the sum concentrations of three chemical classes determined, followed by BTHs (28 %) and BTRs (9 %). The concentrations of all analytes (except for 1-, 4-, and 5-OH-BTRs) exhibited significant positive correlations (r: 0.1-0.9, p < 0.01), suggestive of their common sources and/or similar environmental fates. Higher concentrations of DPGs, BTHs and BTRs were found in soils from highways, rubberized playgrounds, and indoor parking lots than those from gardens, parks, and residential areas. Our findings suggest the release of DPGs, BTHs and BTRs from rubber products, especially automobile tires. Further studies are needed to investigate the environmental fate and toxicities of these chemicals to humans and wildlife.