Faculty Bibliography

Fetal exposure to environmental chemicals has been associated with adverse health outcomes in children and later into adulthood. While several studies have examined correlations and variability of non-persistent chemical exposures throughout pregnancy, many do not capture more recent exposures, particularly in New York City. Our goal was to characterize exposure to phthalates, bisphenols, polycyclic aromatic hydrocarbons, and organophosphate pesticides among pregnant women residing in New York City who enrolled in the New York University Children's Health and Environment Study (NYU CHES) between 2016 and 2018. We measured urinary chemical metabolite concentrations in 671 women at early, mid, and late pregnancy (median 10.8, 20.8, and 29.3 weeks, respectively). We calculated Spearman correlation coefficients among chemical concentrations at each measurement time point. We compared changes in population-level urinary metabolites at each stage using paired Wilcoxon signed-rank tests and calculated intraclass correlation coefficients (ICCs) to quantify intra-individual variability of metabolites across pregnancy. Geometric means and ICCs were compared to nine other pregnancy cohorts that recruited women in 2011 or later as well as nationally reported levels from women of child-bearing age. Compared with existing cohorts, women in NYU CHES had higher geometric means of organophosphate pesticides (Σdiethylphosphates = 28.7 nmol/g cr, Σdimethylphosphates = 57.3 nmol/g cr, Σdialkyl phosphates = 95.9 nmol/g cr), bisphenol S (0.56 μg/g cr), and 2-naphthalene (8.98 μg/g cr). Five PAH metabolites and two phthalate metabolites increased between early to mid and early to late pregnancy at the population level. Spearman correlation coefficients for chemical metabolites were generally below 0.50. Intra-individual exposures varied over time, as indicated by low ICCs (0.22-0.88, median = 0.38). However, these ICCs were often higher than those observed in other pregnancy cohorts. These results provide a general overview of the chemical metabolites measured in NYU CHES in comparison to other contemporary pregnancy cohorts and highlight directions for future studies.

Background/UNASSIGNED:Air pollution, which results in the formation of polycyclic aromatic hydrocarbons (PAHs), has been identified as a cause of renal function decline and a contributor to CKD. However, the results of cross-sectional studies investigating personal, integrated biomarkers of PAHs have been mixed. Longitudinal studies may be better suited to evaluate environmental drivers of kidney decline. The purpose of this study was to examine associations of serially measured urinary PAH metabolites with clinical and subclinical measures of kidney function over time among children with CKD. Methods/UNASSIGNED:-isoprostane) were assayed in urine samples. Results/UNASSIGNED:Children were followed over an average (SD) of 3.0 (1.6) years and 2469 study visits (mean±SD, 4.0±1.6). Hydroxynaphthalene (NAP) or hydroxyphenanthrene (PHEN) metabolites were detected in >99% of samples and NAP concentrations were greater than PHEN concentrations. PHEN metabolites, driven by 3-PHEN, were associated with increased eGFR and reduced proteinuria, diastolic BP z-score, and NGAL concentrations over time. However, PAH metabolites were consistently associated with increased KIM-1 and 8-OHdG concentrations. Conclusions/UNASSIGNED:Among children with CKD, these findings provoke the potential explanation of reverse causation, where renal function affects measured biomarker concentrations, even in the setting of a longitudinal study. Additional work is needed to determine if elevated KIM-1 and 8-OHdG excretion reflects site-specific injury to the proximal tubule mediated by low-grade oxidant stress.

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

Infants born with low or high ("at-risk") birthweights are at greater risk of adverse health outcomes across the life course. Our objective was to examine whether geographic hotspots of low and high birthweight prevalence in New York City had different patterns of neighborhood risk factors. We performed census tract-level geospatial clustering analyses using (1) birthweight prevalence and maternal residential address from an all-payer claims database and (2) domains of neighborhood risk factors (socioeconomic and food environment) from national and local datasets. We then used logistic regression analysis to identify specific neighborhood risk factors associated with low and high birthweight hotspots. This study examined 2088 census tracts representing 419,025 infants. We found almost no overlap (1.5%) between low and high birthweight hotspots. The majority of low birthweight hotspots (87.2%) overlapped with a socioeconomic risk factor and 95.7% overlapped with a food environment risk factor. Half of high birthweight hotspots (50.0%) overlapped with a socioeconomic risk factor and 48.8% overlapped with a food environment risk factor. Low birthweight hotspots were associated with high prevalence of excessive housing cost, unemployment, and poor food environment. High birthweight hotspots were associated with high prevalence of uninsured persons and convenience stores. Programs and policies that aim to prevent disparities in infant birthweight should examine the broader context by which hotspots of at-risk birthweight overlap with neighborhood risk factors. Multi-level strategies that include the neighborhood context are needed to address prenatal pathways leading to low and high birthweight outcomes.

Exposure to endocrine-disrupting chemicals (EDCs) contributes to substantial disease burden worldwide. We aim to quantify the disease burden and costs of EDC exposure in Canada and to compare these results with previously published findings in the European Union (EU) and United States (US). EDC biomonitoring data from the Canadian Health Measures Survey (2007-2011) was applied to 15 exposure-response relationships, and population and cost estimates were based on the 2010 general Canadian population. EDC exposure in Canada (CAD 24.6 billion) resulted in substantially lower costs than the US (USD 340 billion) and EU (USD 217 billion). Nonetheless, our findings suggest that EDC exposure contributes to substantial and costly disease burden in Canada, amounting to 1.25% of the annual Canadian gross domestic product. As in the US, exposure to polybrominated diphenyl ethers was the greatest contributor of costs (8.8 billion for 374,395 lost IQ points and 2.6 billion for 1610 cases of intellectual disability). In the EU, organophosphate pesticides were the largest contributor to costs (USD 121 billion). While the burden of EDC exposure is greater in the US and EU, there remains a similar need for stronger EDC regulatory action in Canada beyond the current framework of the Canadian Environmental Protection Act of 1999.

BACKGROUND:Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. OBJECTIVE:We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age). METHODS: RESULTS: DISCUSSION:We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3-4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077.