Faculty Bibliography

The aim was to investigate the concentrations of some per- and polyfluoroalkyl substances (PFAS) in patients with pancreatic cancer from New York, and to compare them with a group of controls from the general population of the United States. We selected 50 cases of pancreatic cancer from donors to the New York University Pancreatic Biorepository. Controls were selected from the 2017"“18 National Health and Examination Survey sample (n = 167), matched to cases on age, sex, and race and ethnicity. Six PFAS were analyzed in serum samples using high performance liquid chromatography in conjunction with mass spectrometry. PFAS concentrations were categorized into tertiles to explore non-linear associations, and odds ratios (OR) were estimated using conditional logistic regression, adjusting by BMI. Most PFAS were not associated with pancreatic cancer risk. Serum perfluorohexane sulfonic acid (PFHxS) was associated with a decreased risk (OR for upper tertile = 0.24, 95% CI: 0.09, 0.67). In contrast, participants with the highest tertile of perfluoroundecanoic acid (PFUnDA) had a higher risk (OR = 2.60, 95% CI: 1.11, 6.09). Adjusting for BMI did not materially change the results. Study limitations include: in pancreatic cancer patients, blood used to measure PFAS was collected around the time of diagnosis; cases and controls could not be sampled from the same geographic location; slightly different laboratory methods were used to analyze PFAS in cases and controls. Most PFAS studied were not significantly associated with pancreatic cancer, except for PFHxS and PFUnDA, which exhibited opposite trends. Findings and limitations of the present study warrant further investigation with improved study designs and data on complex PFAS mixtures.

BACKGROUND/UNASSIGNED:, a specialized pro-resolving mediator, is suboptimal in higher weight individuals, which may contribute to the clinical trial findings. METHODS/UNASSIGNED:To test this hypothesis, we are conducting a double-blind, placebo-controlled, randomized, mechanistic crossover trial. Healthy men and women exhibiting a wide range of body weights take 81mg aspirin and 325mg aspirin for 3 weeks each, following 3-week placebo run-in and wash-out phases. Our target sample size is 90 subjects, with a minimum of 72 completing all visits estimated to be necessary to achieve power adequate to test our primary hypothesis. RESULTS/UNASSIGNED:occurring with each dose of aspirin. Secondary endpoints include lipid mediator profiles, serum bioactive lipid profiles, and other endpoints involved in the resolution of vascular inflammation. CONCLUSIONS/UNASSIGNED:Study enrollment began in November 2021 and is ongoing. The results of this study will improve our understanding of the mechanisms underlying aspirin's role(s) in the prevention of adverse cardiovascular outcomes. They may also lead to additional studies with the potential to inform dosing strategies for patients based on body weight.

BACKGROUND:A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. METHODS:Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. RESULTS:When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated. CONCLUSIONS:Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals.

RATIONALE & OBJECTIVE/UNASSIGNED:This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). STUDY DESIGN/UNASSIGNED:This was a cross-sectional and longitudinal analysis. SETTING AND PARTICIPANTS/UNASSIGNED:Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). EXPOSURES/UNASSIGNED:Exposure at baseline and longitudinally to various organic chemical pollutants. OUTCOMES/UNASSIGNED:The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. ANALYTICAL APPROACH/UNASSIGNED:We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. RESULTS/UNASSIGNED:and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. LIMITATIONS/UNASSIGNED:Small sample size, evaluation of single rather than combined exposures. CONCLUSIONS/UNASSIGNED:Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.

PURPOSE OF REVIEW: Evidence suggests neurotoxicity of endocrine disrupting chemicals (EDCs) during sensitive periods of development. We present an overview of pediatric population neuroimaging studies that examined brain influences of EDC exposure during prenatal period and childhood. RECENT FINDINGS: We found 46 studies that used magnetic resonance imaging (MRI) to examine brain influences of EDCs. These studies showed associations of prenatal exposure to phthalates, organophosphate pesticides (OPs), polyaromatic hydrocarbons and persistent organic pollutants with global and regional brain structural alterations. Few studies suggested alteration in functional MRI associated with prenatal OP exposure. However, studies on other groups of EDCs, such as bisphenols, and those that examined childhood exposure were less conclusive. These findings underscore the potential profound and lasting effects of prenatal EDC exposure on brain development, emphasizing the need for better regulation and strategies to reduce exposure and mitigate impacts. More studies are needed to examine the influence of postnatal exposure to EDC on brain imaging.

OBJECTIVE:Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. STUDY DESIGN/METHODS:Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. RESULTS:Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. CONCLUSION/CONCLUSIONS:Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.

OBJECTIVE:Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS:We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS:Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION/CONCLUSIONS:In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.

Early infant growth trajectories have been linked to obesity risk. The aim of this study was to examine early infant feeding practices in association with anthropometric measures and risk of overweight/obesity in childhood. A total of 2492 children from Upstate KIDS, a population-based longitudinal cohort, were included for the analysis. Parents reported breastfeeding and complementary food introduction from 4 to 12 months on questionnaires. Weight and height were reported at 2-3 years of age and during later follow-up at 7-9 years of age. Age and sex z-scores were calculated. Linear mixed models were conducted, adjusting for maternal and child sociodemographic factors. Approximately 54% of infants were formula-fed at <5 months of age. Compared to those formula-fed, BMI- (adjusted B, -0.23; 95% CI: -0.42, -0.05) and weight-for-age z-scores (adjusted B, -0.16; -0.28, -0.03) were lower for those exclusively breastfed. Infants breastfed for ≥12 months had a lower risk of being overweight (aRR, 0.33; 0.18, 0.59) at 2-3 years, relative to formula-fed infants. Compared to introduction at <5 months, the introduction of fruits and vegetables between 5 and 8 months was associated with lower risk of obesity at 7-9 years (aRR, 0.45; 0.22, 0.93). The type and duration of breastfeeding and delayed introduction of certain complementary foods was associated with lower childhood BMI.

INTRODUCTION/BACKGROUND:Prenatal exposure to non-persistent chemicals, including organophosphate pesticides, phthalates, and bisphenols, is associated with altered fetal and childhood growth. Few studies have examined these associations using longitudinal growth trajectories or considering exposure to chemical mixtures. METHODS:Among 777 participants from the Generation R Study, we used growth mixture models to identify weight and body mass index (BMI) trajectories using weight and height measures collected from the prenatal period to age 13. We measured exposure biomarkers for organophosphate pesticides, phthalates, and bisphenols in maternal urine at three timepoints during pregnancy. Multinomial logistic regression was used to estimate associations between averaged exposure biomarker concentrations and growth trajectories. We used quantile g-computation to estimate joint associations with growth trajectories. RESULTS:Phthalic acid (OR: 1.4, 95% CI: 1.01, 1.9) and bisphenol A (BPA; OR: 1.5, 95% CI: 1.0, 2.2) were associated with higher odds of a growth trajectory characterized by smaller prenatal and larger childhood weight relative to a referent trajectory of larger prenatal and average childhood weight. Biomarkers of organophosphate pesticides, individually and jointly, were associated with lower odds of a growth trajectory characterized by average prenatal and lower childhood weight. CONCLUSIONS:Exposure to phthalates and BPA was positively associated with a weight trajectory characterized by lower prenatal and higher childhood weight, while exposure to organophosphate pesticides was negatively associated with a trajectory of average prenatal and lower childhood weight. This study is consistent with the hypothesis that non-persistent chemical exposures disrupt growth trajectories from the prenatal period through childhood.

BACKGROUND:Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES:We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS:We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS:Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [β -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS:Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.