Faculty Bibliography

OBJECTIVES/OBJECTIVE:Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS:In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS:Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS:Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.

CONTEXT/BACKGROUND:Phthalates are commonly found in commercial packaging, solvents, vinyl, and personal care products, and there is concern for potential endocrine-disrupting effects in males. The commonly used di-2-ethylhexyl phthalate (DEHP) has progressively been replaced by seldom studied compounds, such as bis-2-ethylhexyl terephthalate and 1,2-cyclohexane dicarboxylic acid di-isononyl ester (DINCH). OBJECTIVE:To investigate the associations between the urinary phthalate metabolites and serum sex steroid hormone concentrations in a nationally representative sample of adult males. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION/UNASSIGNED:This was a cross-sectional analysis of data from the 2013-2016 National Health and Nutrition Examination Survey among 1420 male participants aged ≥20 years. MAIN OUTCOME MEASURES/METHODS:Serum levels of total testosterone, estradiol, sex hormone binding globulin, and derived sex hormone measurements of free testosterone, bioavailable testosterone, and free androgen index were examined as log-transformed continuous variables. RESULTS:Phthalate metabolites were not statistically significantly associated with sex hormone concentrations among all men. However, associations varied by age. High molecular weight phthalates were associated with lower total, free, and bioavailable testosterone among men age ≥60. Specifically, each doubling of ΣDEHP was associated with 7.72% lower total testosterone among older men (95% Confidence Interval: -12.76%, -2.39%). Low molecular phthalates were associated with lower total, free, and bioavailable testosterone among men age 20-39 and ΣDINCH was associated with lower total testosterone among men age ≥40. CONCLUSIONS:Our results indicate that males may be vulnerable to different phthalate metabolites in age-specific ways. These results support further investigation into the endocrine-disrupting effects of phthalates.

Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence on the association between prenatal PFAS exposure and child neurodevelopment is limited and inconsistent. This study evaluated the association between prenatal PFAS exposure and child cognitive outcomes measured at 5 different time points in a population prenatally exposed to the WTC disaster. The study population included 302 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at three hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. We evaluated the association between prenatal exposure to four PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA)) and child neurodevelopment measured using the Bayley Scales of Infant Development (BSID-II) at approximately 1, 2 and 3 years of age and using The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at approximately 4 and 6 years of age. Geometric mean (range) concentrations of PFAS were 6.03 (1.05, 33.7), 2.31 (0.18, 8.14), 0.43 (<LOQ, 10.3) and 0.67 (<LOQ, 15.8) ng/mL for PFOS, PFOA, PFNA and PFHxS, respectively. Several PFAS were associated with increases in cognitive outcomes in females and overall (males and females combined). Child sex modified the association between PFOS and the mental development index measured using BSID-II, with the observed relationship being positive for females and negative for males. Through principal component analyses, we observed a negative relationship between PFNA and the psychomotor development index measured using BSID-II and the verbal IQ measured using WPPSI. Our results suggest a sex- and compound-specific relationship between prenatal PFAS exposures and childhood neurodevelopment.

Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.

BACKGROUND:Few resources exist for prospective, longitudinal analysis of the relationships between early life environment and later obesity in large diverse samples of children in the United States (US). In 2016, the National Institutes of Health launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate influences of environmental exposures on child health and development. We describe demographics and overweight and obesity prevalence in ECHO, and ECHO's potential as a resource for understanding how early life environmental factors affect obesity risk. METHODS:In this cross-sectional study of 70 extant US and Puerto Rico cohorts, 2003-2017, we examined age, race/ethnicity, and sex in children with body mass index (BMI) data, including 28,507 full-term post-birth to <2 years and 38,332 aged 2-18 years. Main outcomes included high BMI for age <2 years, and at 2-18 years overweight (BMI 85th to <95th percentile), obesity (BMI ≥ 95th percentile), and severe obesity (BMI ≥ 120% of 95th percentile). RESULTS:The study population had diverse race/ethnicity and maternal demographics. Each outcome was more common with increasing age and varied with race/ethnicity. High BMI prevalence (95% CI) was 4.7% (3.5, 6.0) <1 year, and 10.6% (7.4, 13.7) for 1 to <2 years; overweight prevalence increased from 13.9% (12.4, 15.9) at 2-3 years to 19.9% (11.7, 28.2) at 12 to <18 years. ECHO has the statistical power to detect relative risks for 'high' BMI ranging from 1.2 to 2.2 for a wide range of exposure prevalences (1-50%) within each age group. CONCLUSIONS:ECHO is a powerful resource for understanding influences of chemical, biological, social, natural, and built environments on onset and trajectories of obesity in US children. The large sample size of ECHO cohorts adopting a standardized protocol for new data collection of varied exposures along with longitudinal assessments will allow refined analyses to identify drivers of childhood obesity.

The aims of the NYU Children's Health and Environment Study (CHES) are to evaluate influences of prenatal non-persistent chemical exposures on fetal and postnatal growth and pool our data with the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program to answer collaborative research questions on the impact of the preconceptual, prenatal, and postnatal environment on childhood obesity, neurodevelopment, pre/peri/postnatal outcomes, upper and lower airway outcomes, and positive health. Eligible women were ≥ 18 years old, < 18 weeks pregnant, had a pregnancy that is not medically threatened, and planned to deliver at NYU Langone Hospital-Manhattan, Bellevue Hospital, or NYU Langone Hospital-Brooklyn. Between March 22, 2016 and April 15, 2019, we recruited 2469 pregnant women, from whom 2193 completed an initial questionnaire and continued into NYU CHES. Of the 2193, 88 miscarried, 28 terminated, and 20 experienced stillbirth, while 57 were lost to follow up. We report here demographic and other characteristics of the 2000 live deliveries (2037 children), from whom 1624 (80%) consented to postnatal follow-up. Data collection in pregnancy was nested in clinical care, with questionnaire and specimen collection conducted during routine prenatal visits at < 18, 18-25, and > 25 weeks gestation. These have been followed by questionnaire and specimen collection at birth and regular postpartum intervals.

It is hypothesized that chronic kidney disease (CKD) induces oxidant stress which contributes to the decline in kidney function. However, few studies have incorporated longitudinal designs and no studies have investigated this association among children. Using data from the Chronic Kidney Disease in Children (CKiD) study, we examined longitudinal associations between urinary biomarkers of oxidant stress, 8-OH deoxyguanosine (8-OHdG) and F2-isoprostane, and measures of renal function and blood pressure among children with CKD. Baseline levels of 8-OHdG were positively associated with estimated glomerular filtration rate (eGFR) over time and a log-unit increase in baseline 8-OHdG predicted a 5.68 ml/min/1.73 m² increase in eGFR (95% Confidence Interval (CI): 3.75, 7.61). This association was attenuated when longitudinal measures of 8-OHdG were analyzed in relation to longitudinal eGFR (per log-unit increase in 8-OHdG, β = 0.81, 95% CI: 0.22, 1.39). Baseline 8-OHdG concentrations were also associated with decreased proteinuria over time, as measured by urinary protein:creatinine ratio. In addition, F2-isoprostane concentrations were associated with increases in eGFR, but only when baseline levels (vs. longitudinal levels) were considered in relation to longitudinal eGFR. There were no significant associations between either 8-OHdG or F2-isoprostane and blood pressure over time. Urinary measures of oxidant stress are not associated with worsening GFR over time. Our findings suggest that excretion of these biomarkers may be influenced by changes in glomerular and tubular function in varying patterns, which would limit their value in evaluating the impact of oxidant stress on CKD progression in children.

INTRODUCTION/BACKGROUND:Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence suggests PFAS may have cardiometabolic effects, including alterations in lipid profiles. This study evaluated the association between cord PFAS and lipids in a population prenatally exposed to the WTC disaster. STUDY POPULATION/METHODS:222 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. METHODS:We evaluated the association between five cord blood PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecane sulfonate (PFDS)) and cord blood lipids (total lipids, total cholesterol, triglycerides). RESULTS:Median (interquartile range (IQR)) concentrations of PFAS were 6.32 (4.58-8.57), 2.46 (1.77, 3.24), 0.38 (0.25, 0.74), 0.66 (0.48, 0.95) and 0.11 (0.09, 0.16) ng/mL for PFOS, PFOA, PFNA, PFHxS and PFDS, respectively. Median (IQR) for lipids were 59.0 (51.5, 68.5) mg/dL for total cholesterol, 196.5 (170.5, 221.2) mg/dL for total lipids and 33.1 (24.2, 43.9) mg/dL for triglycerides. In fully adjusted models, several PFAS were associated with higher lipid levels, including evidence of a strong linear trend between triglycerides and both PFOA and PFHxS. CONCLUSIONS:Findings support previous evidence of an association between PFAS exposure and altered lipid profiles and add novel information on this relationship in cord blood, as well as for an understudied PFAS, PFDS.

The clinical management of well-appearing febrile infants 7-60 days of age remains variable due in part to multiple criteria differentiating the risk of a serious bacterial infection. The purpose of this quality improvement study was to standardize risk stratification in the emergency department and length of stay in the inpatient unit by implementing an evidence-based clinical practice guideline (CPG).