Title of Project: Children’s Urinary miRNAS as Biomarkers of Early Life Metal Exposure
Principal Investigator: Alison P Sanders, PhD

Co-Investigators: Lisa Satlin, MD; Robert Wright, MD, MPH; Chris Gennings, PhD

Project Period: October 2016 – September 2017

Pilot Award Amount: $70,000

 

Abstract: Toxic metals including cadmium (Cd), mercury (Hg), and lead (Pb) are known renal toxicants in adults; however, their renal toxicity in developing children is understudied. Prenatal and early childhood are potential susceptibility windows for renal toxic metals as these life stages are associated with development and differentiation of renal transport systems. Urinary microRNAs (miRNAs) serve as early biomarkers of renal health, and may mediate metal-associated health effects. The aims of this study are to compare miRNA expression in children’s whole urine and urinary exosomes, and determine whether early life toxic metal exposure contributes to altered miRNA expression. To accomplish our goals, we will leverage an existing and established longitudinal birth cohort in Mexico City – the Programming Research in Obesity, GRowth Environment and Social Stress (PROGRESS) study – which has measured prenatal and childhood levels of metals (Cd, Hg, and Pb) longitudinally in blood and nails, and collected urine from mother-child pairs at each visit. This proposal therefore need only measure miRNA expression as well as concurrent metal and creatinine levels in urine. The research team includes expertise in pediatrics, metals toxicology, epidemiology, biostatistics, and epigenetics, including Drs. Alison Sanders, Lisa Satlin, Chris Gennings, and Robert Wright. This proposal leverages P30 Core Center expertise in children’s environmental health and biostatistics (Preventive Medicine) with specialization in renal physiology and epigenetics (Pediatrics and Pittsburgh Center for Kidney Research). This work will advance our ability to assess miRNAs as biomarkers and/or specific mechanisms that may contribute to metal-altered pathophysiology of renal health. The proposed research activities will provide substantial pilot data for future R01 applications to assess the functional impacts of early life metal exposure on miRNAs that maymediate renal/cardiovascular outcomes, and lead to future interventions designed to prevent or treat renaltoxic metal exposure.

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Title of Project: Prenatal manganese exposure, placental imprinting, and fetal growth: a pilot study

Principal Investigator: Jia Chen, ScD

Co-Investigators: R. Colin Carter, MD, MMSc; Sandra Jacobson, PhD; Joseph Jacobson, PhD; Pei Wang, PhD; Christopher Molteno, MD

Project Period: October 2016 – September 2017

Pilot Award Amount: $25,000

 

Abstract: Manganese (Mn) is both an essential nutrient and a toxicant, with environmental exposure via air, water, and soil, particularly in areas where Mn is either mined, transported, or added to gasoline as methylcyclopentadienyl manganese tricarbonyl (MMT), an anti-knocking agent. Prenatal exposure to both high and low levels of manganese has been shown to impair fetal growth and neurodevelopment. Recent evidence has implicated alterations in epigenetic programming as a potential mechanism in these effects, and alterations in the expression profiles of imprinted genes in the placenta may be of particular importance, given the critical roles of these genes in fetal growth and neurodevelopment. We hypothesize that prenatal Mn exposure modulates imprinted gene expression that leads to deficits in fetal growth. We will test this hypothesis in banked placenta samples obtained from 68 mother-infant pairs in a prospective longitudinal cohort study examining the effects of prenatal alcohol exposure on growth and development, including both drinkers and abstaining controls. Placental Mn content (mg/g dried placental tissue) will be measured using ICP-MS, and placental expression of imprinted genes will be assayed using a validated, multiplexed imprintome assay by nanoString. This cohort was recruited in Cape Town, South Africa, where Mn exposure levels are particularly high due to Mn mining and the addition of MMT to gasoline. A major strength of our approach is the measurement of Mn content directly in the target tissue, the placenta, as blood concentrations of Mn may not correlate with degree of environmental exposure. The placenta is an ideal target tissue for this study because it is fetally-derived, and imprinted genes are highly expressed in the placenta. Furthermore, prospectively obtained data regarding prenatal alcohol exposure will provide a unique opportunity to explore potential interactions between Mn and
alcohol, which have similar effects on fetal growth and neurobehavior.

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Title of Project: Air Pollution and Psychosocial stress exposure during pregnancy, telmere length and respiratory health in childhood

Principal Investigator: Maria José Rosa, DrPH

Co-Investigators:  Rosalind Wright, MD, MPH; Allan Just, PhD; Andrea Baccarelli, MD, PhD

Project Period: October 2016-September 2017

Pilot Award Amount: $25,000

 

Abstract: In utero exposure to ambient pollution and psychosocial stress may adversely affect the developing respiratory system. Despite the long history of research on these 2 issues, the underlying mechanism of their effects has not been completely elucidated. Telomeres play a critical role in cellular aging and appear to be particularly sensitive to reactive oxygen species (ROS) damage. Decreased length may represent a common underlying mechanism connecting fetal programming and subsequent adverse respiratory outcomes shared by both exposures. Newborn telomere length may be of particular importance. Our group has estimated daily predicted values of particulate matter <2.5 microns in diameter (PM2.5) during pregnancy for each of the participants enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. We have also collected prospective measures of stress during pregnancy and children’s respiratory health. In this proposal we will measure leukocyte telomere length (LTL) in cord blood DNA, as an index of cumulative ROS and cellular aging during pregnancy. We predict that children with higher exposure to prenatal PM2.5/stress will have shorter LTL, and shorter LTL will be associated with greater risk of asthma/wheeze in childhood, with LTL potentially mediating the effects between air pollution/stress and asthma/wheeze.

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Title of Project: NICU-BASED LEAD EXPOSURE AND BIOMARKERS OF IMPAIRED RENAL HEALTH

Principal Investigator: Alison P. Sanders, PhD

Co-Investigators: Lisa Satlin, MD; Annemarie Stroustrup, MD; Chris Gennings, PhD; Andrea Weintruab, MD; Robert Wright, MD, MPH;

Project Period: October 2016-September 2017

Pilot Award Amount: $25,000

 

Abstract: Emerging evidence suggests that renal disease can develop from subclinical insults in fetal life or early childhood. During these critical periods for differentiation of the renal filtration, secretion, and reabsorptive systems, environmental exposures may alter the developmental trajectory of the kidney resulting in hypertension and renal disease. Most research on Pb nephrotoxicity has been conducted in adults; Pb nephrotoxicity in developing children remains understudied. Preterm infants are particularly susceptible to renal damage, because birth occurs prior to the completion of nephron formation. We recently noted that prenatal Pb exposure among preterm infants is associated with increased blood pressure at 4 years of age. We also know that, unexpectedly, Pb exposure is common in the NICU environment. We propose to build upon these important findings by measuring prenatal and NICU-based Pb exposure and examining both clinical AND preclinical biomarkers of renal dysfunction among a susceptible population of preterm infants. We hypothesize that early life Pb exposure contributes to renal dysfunction in preterm infants. We are poised to address the impact of prenatal and early childhood Pb exposure during critical windows of renal development using the NICU Hospital Exposures and Long-Term Health cohort (NICU-HEALTH). Preterm infants born between 28 and 33 weeks gestation are enrolled in NICU-HEALTH and followed through early childhood. We will use maternal blood and neonatal urine samples to measure Pb and selected biomarkers of renal dysfunction, and will collect other renal parameters (serum creatinine and blood pressure). We will analyze associations between Pb exposure and renal outcomes individually and in combination. This work will: i) inform our understanding of biomarkers for subclinical renal toxicity, and ii) identify risk factors for early life origins of kidney disease and hypertension, potentially leading to future interventions designed to prevent or treat nephrotoxic Pb exposure in susceptible populations.

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Title of Project: Early-life exposure to inorganic arsenic exacerbates the development of fatty
liver disease

Principal Investigator: Kathryn Bambino, PhD

Co-Investigators: Christine Austin, PhD; Jaime Chu, MD; Manish Arora, BDS, MPH, PhD; Christoph Buettner, MD, PhD

Project Period: October 2016-September 2017

Pilot Award Amount: $25,000

 

Abstract:Prenatal and childhood exposure to inorganic arsenic (iAs) leads to increased risk of mortality, cancer andmetabolic disease, putting iAs at the #1 position on the American Toxic Substances and Disease Registry(ATSDR) watch list. However, despite solid epidemiological evidence demonstrating the adverse and long-termhealth effects of early life exposure to iAs, the mechanism by which iAs causes disease are relatively unknown.Surprisingly, only a few studies in animals have examined specific outcomes associated with iAs exposure. While the idea that environmental exposures modify the severity of common diseases, such as diabetes and obesity, has been widely discussed, few studies have addressed this possibility directly. Here, we will do this using zebrafish to identify the mechanistic basis of iAs toxicity in metabolic disease. Fatty liver is the hepatic manifestation of metabolic syndrome and is also caused by alcohol abuse. However, not all people who drink excessively develop fatty liver disease (FLD). A widely proposed but untested hypothesis is that additional environmental exposures synergize with ethanol to cause FLD. Our preliminary data shows that iAs is sufficient to cause FLD accompanied by activation of the unfolded protein response, a pathway that has been shown to be a common, causative mechanism to alcoholic and non-alcoholic fatty liver. We found that exposure to a low dose of iAs during early development synergistically interact with ethanol to cause steatosis, activate the UPR, and cause severe toxicity and lethality. In summary, our work promotes the idea that iAs toxicity is mediated by activation of a pathological UPR. Moreover, an exciting potential outcome of our findings is the idea that iAs synergizes with alcohol, thereby providing a basis to understand the diverse outcomes of alcohol abuse. Further studies will seek to elucidate the mechanism by which early-life exposure to iAs leads to progressive liver disease.

 

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Title of Project: Psychosocial motivations, behavioral patterns, and health effects of metal, hydroquinone, and steroid exposure associated with skin bleaching among African and Afro-Caribbean women in New York City
Principal Investigator: Bian Liu, PhD

Co-Investigators: Emma Benn, DrPH, Nihal Mohamed, PhD, Andrew Alexis, MD, MPH

Project Period: October 2016 – September 2017

Pilot Award Amount: $25,000

 

Abstract: Skin bleaching practices, such as using skin creams and soaps to achieve a lighter skin tone, are common throughout the world, and are triggered by cosmetic reasons that oftentimes have deep historical, economic, sociocultural, and psychosocial roots. Exposure to chemicals in the bleaching products, notably, mercury (Hg), hydroquinone (HQ), and steroids, has been associated with a variety of adverse health effects, such as mercury poisoning and exogenous ochronosis. In New York City (NYC), skin care product use has been identified as an important route of Hg exposure, especially among Caribbean-born blacks and Dominicans. However, surprisingly sparse information is available on the epidemiology of the health impacts of skin bleaching practices among these populations. This pilot project serves as the necessary initiation of a future research agenda to address the knowledge gaps surrounding skin bleaching practices and health outcomes among African and Afro-Caribbean women in NYC. To that end, we will identify a study population with typical clinical presentations indicative of skin bleaching through reviews of the pathology database and medical charts of patients who visited the Skin of Color Center at Mount Sinai. Detailed interviews will be conducted to explore skin practices (i.e., type and frequency of products used), self-reported health problems commonly resulting from skin bleaching, and psychosocial factors that may influence this behavior. Exposure assessment will be conducted based on laboratory measurement of metals, HQ, and steroids in skin bleaching products, and questionnaire responses. We expect a heterogeneous pattern of the skin bleaching practices; and hypothesize that chronic users are at a higher risk of having more severe symptoms. Results from this pilot study will serve as preliminary data to obtain extramural funding for an in-depth investigation of the health effects of skin bleaching practices among non-White populations, and to identify effective and culturally sensitive strategies for intervention.

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Title of Project: Exposure Characterization to Crumb Rubber used in Artificial Turf Fields: A

Principal Investigator: Homero Harari, ScD

Co-Investigators: Sarah Evans PhD, Maida Galvez MD MPH, Robert Wright MD MPH

Project Period: October 2016-September 2017

 

Abstract: Crumb rubber infill, generated by grinding recycled rubber automobile tires into small pellets, is utilized on thousands of athletic playing surfaces worldwide. Several reports showed that recycled tires contain known carcinogens, neurotoxins, and other chemicals of concern, yet comprehensive exposure and risk assessment has not been conducted. Existing studies have not characterized exposures during realistic play conditions or addressed dermal and oral routes of exposure to potentially harmful chemicals. Concerns about the health risks associated with exposures to chemicals resulting from play on crumb rubber are mounting. As a result, the Mount Sinai Children’s Environmental Health Center (CEHC) and Region 2 Pediatric Environmental Health Specialty Unit (PEHSU) receive numerous calls for consultation about the risk of artificial turf surfaces; however gaps in the scientific data make it difficult to guide communities in risk reduction. Recent media reports of young soccer goalies diagnosed with lymphomas and other cancers have prompted a federal study of the safety of crumb rubber, on the basis that existing studies are limited. The aims of this proposal are to 1) characterize chemicals of concern in crumb rubber used in turf fields, and 2) characterize exposure in real playing conditions. The project will be conducted via partnership with a community partner who regularly utilizes crumb rubber turf fields. Individual and aggregate exposure assessment findings will be reported back to participants. Based on our exposure assessment findings, we will work closely with users to develop feasible and effective risk reduction methods and associated communication strategy. This proposal will serve as a pilot for future grant applications to examine exposures on a larger number of crumb rubber fields as well as exposures in children. Future studies will examine the risks of exposure to identified chemicals of concern both individually and in aggregate. In addition, our findings will provide a framework for effective communication with communities regarding the safety of crumb rubber artificial turf.

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Title of Project: Prenatal Ambient Air Pollution Exposure And Long Noncoding Rnas In Breast Milk Extracellular Vesicles

Principal Investigator: Alison Lee, MD

Co-Investigators:

Project Period: October 2016-September 2017

 

Abstract: Air pollution is a major health concern and accounts for 3.7 million deaths annually. The developing lung is particularly susceptible to air pollution exposures. In utero exposure to ambient air pollution has been associated with childhood wheeze, asthma onset and morbidity as well as reduced lung function. Psychosocial stress, a risk factor that may co-vary with exposure to air pollutants in high-risk urban communities, can enhance air pollution effects. However, the mechanisms by which air pollution alters lung development and predisposes children to increased future risk of respiratory disease are largely unknown. Extracellular vesicles (EVs) and their cargo, specifically long noncoding RNA (lncRNA), play central roles in cell-to-cell and inflammatory signaling and have been demonstrated to both be modified by preceding air pollution exposures and predict future lung function decline. Our group has identified a number of developmentally-related EV lncRNAs in human breastmilk supporting the hypothesis that these EV lncRNAs may mediate the association between prenatal air pollution and stress exposures and future child respiratory disease risk. Using our Perinatal Environmental and Development Study (PEDS) cohort with state of the art characterization of prenatal ambient fine particulate matter mass (PM2.5) and maternal stress exposures in addition to important covariates, we are uniquely poised to address this question. We predict that prenatal ambient PM2.5 and maternal stress are independently associated with specific profiles of breast milk lncRNAs and that the association between prenatal ambient PM2.5 and breast milk lncRNAs is modified by prenatal maternal stress

The Center’s mission is to increase the Environmental Health (EH) research portfolio at Mount Sinai and to bring non-EH researchers into the field through new transdisciplinary collaborations.

Title: “Predicting Neurotoxic Perturbations of Developmental Neuroplasticity via an Integrative Bioinformatics Approach”

PI: Joel Dudley

Neurodevelopment is marked by periods of activity-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are perturbed, optimization of function (i.e. visual acuity or language) can be permanently disrupted. A major clinical and scientific gap is knowledge of environmental neurotoxicants that disrupt critical period biology. Historically, this knowledge has been limited by a lack of a comparable data shared between perturbagens and in vivo neuroplasticity and a lack of methods to systematically identify connections between the data. Here, we propose a novel integrative bioinformatics approach that leverages the exponential growth in public molecular data. Our goal is to systematically identify toxicants that suppress networks and pathways regulating critical periods of developmental neuroplasticity. In our preliminary study, we derived in vivo neuroplasticity signatures from mice with elevated plasticity in visual cortex, a well-established model of critical period plasticity. We then computationally matched these transcriptional signatures of in vivo neuroplasticity to >2500 curated toxicant gene set modules. We found overrepresentation of known (i.e. lead, toluene, arsenic, chlorpyrifos, methlymercury, PCBs) and novel neurotoxicants with neuroplasticity signatures. These results have led us to hypothesize that known (and novel) neurotoxicants will disrupt critical period neuroplasticity and result in molecular and functional consequences to neurological and cognitive development. We will test this hypothesis by first developing and applying an integrative informatics approach to identify and prioritize neurotoxicants based on transcriptional profiles (Aim1). We will then assess effect of known neurotoxicant (Pb2+) on developmental neuroplasticity using a well-characterized in vivo model of neuroplasticity (mouse visual system) (Aim2). Lastly, we will validate transcriptome-wide effect of anti-plasticity toxicants (Aim3). This work will establish the detrimental role of known neurotoxicants in developmental neuroplasticity and lay the groundwork for systematic, data-driven prediction and screening of novel neurodevelopmental toxicants.

 

Title: “Assessment of past phthalate exposure in adult rats using teeth microstructure analysis”

PI: Syam Andra

In this project we will use teeth microstructure analysis as a biomarker of past phthalate exposure in adult rats exposed in early life during critical windows for reproductive and metabolic programming. Wistar rat dams (N=12 litters/group) will be treated with vehicle control and 3 doses of either di-2(ethylhexyl) (DEHP) or di-nbutyl phthalate (DnBP) (0.018, 0.18, and 1.8 mmol/kg/day) from gestation day 13 to postnatal day 21 (weaning). Using an innovative approach based on tooth ontogeny and histological landmarks we will determine the concentrations of DEHP and DnBP metabolites in time-specific dentine layers of adult offspring rats reflecting in utero and lactational exposure. The techniques will combine fine microdissection of first mandibular rat teeth and analysis of phthalate metabolites by state-of-the-art high performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS). In addition, we will examine dose-responses for reproductive and metabolic effects in male rats, in particular disruption of androgen-dependent development and altered glucose homeostasis, and possible associations between these endpoints and internal phthalate doses assessed by teeth analysis. Overall, the transdisciplinary team of researchers involved in this project will combine unique expertise in the fields of developmental toxicology, epidemiology and analytical chemistry to establish an animal model that will validate the use of teeth as exposure biomarker that can assess longterm/late-onset effects of phthalates in relation to past exposure. The results obtained will reinforce the use of teeth as a potential biomarker of exposure in both animal and human studies, including ongoing birth cohort studies coordinated by the Department of Preventive Medicine at Mount Sinai.

 

Title: “Lead Exposure And Addictive Diseases: A Pilot Study Of The Association Between Tibia-Lead And Cocaine Addiction”

PI: Megan Horton

While researchers recognize several known risk factors for adult drug addiction (i.e., family history of addiction, physical and sexual abuse, depression and other co-morbidities), the role exposure to environmental chemicals may play in drug addiction has not been well studied. In this study, we propose to examine the association between environmental exposure to the heavy metal, lead, and cocaine addiction. The welldocumented neurotoxic cognitive and behavioral effects of environmental lead (Pb) exposure are attributed, in part, to disruption of the mesolimbic dopaminergic (DA) system. Animal studies demonstrate that low level Pb exposure results in excess synaptic DA, with consequent down-regulation of postsynaptic DA receptors. Disrupted DA function is a major player in mediating drug reward behaviors and the development of addiction to drugs of abuse, such as cocaine. Cocaine produces its immediate psychological effect by causing a build up of synaptic DA. We hypothesize that cumulative exposure to Pb is associated with increased drug seeking behaviors and a greater likelihood of cocaine addiction in humans. To test this hypothesis, we propose to pilot a case-control study of cocaine addicts and healthy controls enrolled in the ongoing Neuroimaging of Addiction and Related Conditions (NARC) Research Program. Using 109Cd-based K-shell X-Ray Fluorescence (XRF), we will measure cumulative Pb exposure in cases and controls and examine associations between Pb exposure and the neuropsychological and neuroimaging phenotypes of cocaine addiction. This study will help elucidate a novel toxicology-related mechanism of addiction, with potential applications to other disorders of self-regulation that are similarly characterized by compromised DA signaling, as well as to other environmental chemicals that act on the DA system. Results could inform insight into interventions addressing the environmental risk factors associated with vulnerability to addiction.

 

Title: “AIR QUALITY IN THE NEONATAL INTENSIVE CARE UNIT”

PI: Annemarie Stroustrup

Each year in the United States, over 300,000 neonates require admission to a neonatal intensive care unit (NICU) where they are exposed to a chemical-intensive hospital environment. Preterm infants spend a particularly vulnerable developmental period corresponding to the third trimester in the NICU. It is known that exposure to air pollutants including volatile organic compounds (VOCs) during fetal and early postnatal life can permanently alter pulmonary and neurobehavioral outcomes in children born at term. We also know that NICU graduates experience pulmonary and neurodevelopmental abnormalities at higher rates than the general population and may represent a highly vulnerable subpopulation for toxic chemical exposure. Neurodevelopmental and pulmonary disorders among NICU graduates are incompletely predicted by degree of prematurity or neonatal illness. There are no comprehensive studies of chemical exposure in the NICU. We do not understand the impact of hospital-based chemical exposure on clinical outcomes of NICU graduates. Specific source(s) and types of exposure need to be identified in order to mitigate potential adverse outcomes. We propose to leverage the NICU-Hospital Exposures And Long-Term Health (NICU-HEALTH) study to characterize inhalational chemical exposure in the NICU. The NICU-HEALTH study is an active prospective birth cohort study of moderately preterm infants in the Mount Sinai NICU. Information on exposure to medical materials and stress as well as serial biospecimens are collected from each infant throughout the NICU hospitalization. Short-term outcomes include growth and neurodevelopmental progress; long-term outcomes of neurodevelopment and pulmonary function are planned. No measures of air quality (AQ) are currently included in the NICU-HEALTH protocol. In the proposed study we will (1) evaluate both ambient AQ in the NICU and AQ inside the neonatal incubator; and (2) evaluate the association of AQ in the neonatal incubator with concurrent oxidative stress in hospitalized moderately preterm infants.

 

Title: “In utero chemical and non-chemical stressors, sex hormones, and infant neurodevelopment”

PI: Rosalind J. Wright

Despite increasing evidence that developing males and females respond differently to chemical and nonchemical stressors, few studies directly examine sex-specific effects of neurotoxicants. Moreover, the mechanisms underlying sex-specific effects of these toxicants are poorly understood. Chemicals and psychological stress both impact sex hormone physiology and differential exposure to sex steroids during prenatal development (e.g. altered testosterone, estradiol, progesterone levels) may represent a pathway to sex differences in neurodevelopment. Research in this area to date has been limited by a reliance on sex steroid assessment in single sample of saliva or amniotic fluid which can only represent sex steroid level over short periods of time. The proposed pilot analyses will take advantage of banked maternal saliva and hair samples from a subset (n=140) of mother-infant dyads participating in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study to assess both diurnal fluctuations in sex steroids (representing daily rhythms of salivary testosterone, progesterone, and estradiol) and longer-term trait-like sex steroid levels measured in mothers’ hair collected shortly following delivery (representing integrated average levels over trimesters). The joint distribution of hair and salivary sex steroids will be assessed using advanced statistical approaches; combinations of sex steroid measures that are best associated with prenatal maternal stress and/or chemical exposures (metals, endocrine disrupting chemicals) will be determined. Associations between identified composite sex steroid indices and infant temperament, an early marker of infant neurodevelopment, will also be explored. We will compare the relative effectiveness of these derived prenatal sex steroid indices with respect to early neurobehavioral outcomes compared with conventional methods (single salivary measure or hair measure alone). This is the first study to assess the combined contributions of sex steroids measured in repeated saliva samples providing diurnal variation and in hair recreating exposure over the course of pregnancy in a longitudinal study examining infant neurodevelopment.

The newly funded Mount Sinai NIEHS Core Center announced its first call for Pilot Grant proposal in December 2014. The Center’s mission is to increase the Environmental Health (EH) research portfolio at Mount Sinai and to bring non-EH researchers into the field through new transdisciplinary collaborations.

Title: Novel Tissue Elemental bio-Imaging to Study the Role of Environmental Pollutants in Type I Diabetes

PI: Dr. Manish Arora

There is a well-documented rise in the incidence of type 1 diabetes (T1D) in children from industrialized countries suggesting a role for environmental chemical exposures. Alarmingly, the increased incidence is seen mostly in children under age 5. However, research on environmental chemical exposures and T1D is very limited and there is an urgent need for research to fill this gap in our knowledge. Therefore, the goal of this proposal is to identify environmental pollutants that play a role in the increased incidence of T1D in children. Identifying the causes of the increasing incidence of T1D in children will enable us to develop prevention strategies based on the mechanisms causing the disease.

Title: Autism Spectrum Disorders and Prenatal Persistent Organic Pollutants (ASD-POP)

PI: Dr. Avi Reichenberg

There is an urgent need to understand the role of environmental factors in the risk for Autism Spectrum Disorders (ASD). Prenatal exposure to several classes of chemicals, including pharmaceuticals, has been examined in relation to ASD risk. Increased risk of ASD was recently reported for prescribed mood stabilizers (SSRIs and Valproate). However, pregnant women and fetuses are exposed to many pollutants in addition to pharmaceuticals, and for most of these the risk of ASD has scarcely been characterized. To address this, population-based investigations are required that can adequately examine the role of prenatal exposure to environmental chemicals in ASD etiology. This project will help establish the necessary preliminary work to accurately and precisely estimate the contribution of prenatal POPs exposure to the etiology of ASD.

Title: Air Pollution Exposure During Pregnancy and Respiratory Health in Childhood

PI: Dr. Rosalind Wright

In utero exposure to ambient pollution may adversely affect the developing respiratory system. Despite the long history of research on this issue, very little is known regarding which life stages are most susceptible. The identification of windows of susceptibility in pregnancy or in childhood would direct the appropriate timing of public health efforts and could direct researchers to more efficiently elucidate the mechanisms through which ambient air pollution is associated with respiratory morbidity, as the timing for assessments would be evidence based. We predict that children with higher exposure during this window will have lower lung function measures and higher levels of airway inflammation. We will also explore a potential interaction between ambient air pollution and psychosocial stressors.

Title: Neuroimaging Phenotypes of Prenatal and Early Childhood Exposure to Manganese

PI: Dr. Megan Horton

Modern neuroimaging tools such as magnetic resonance imaging have been used to characterize the development of normal brain processes and to understand the neuropathological and neurofunctional correlates of developmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder. Only recently, these neuroimaging tools have been applied to epidemiologic studies of children’s environmental health to begin to explore the neuropathological and neurofunctional mechanisms by which exposure to environmental toxicants derail normal neurodevelopment. In this study, we propose to examine the neuroimaging phenotypes associated with prenatal and childhood exposure to manganese (Mn). Several recent environmental epidemiologic studies extend these findings to children revealing inverse associations between early life exposure and childhood cognition, behavior and motor skills. To date, no studies have investigated the neural correlates of Mn-induced neurodevelopmental toxicity in children.

Title: Leveraging Big Data and Machine Learning to Assess the Effects of Multiple Air Toxics on Cognitive Outcomes in Children

PI: Dr. Gaurav Pandey

Epidemiologic studies have shown that prenatal exposures to ambient air pollutants are associated with neurodevelopment and behavior in infants and children. Although ambient air is a complex mixture of multiple pollutants, most previous research has focused on the effects of individual pollutants on children’s cognitive health. Machine learning techniques present a new opportunity to examine the joint effects of multiple air pollutants on cognitive outcomes, but there has been limited implementation of these techniques in air pollution epidemiology. Overall, this pilot will establish the feasibility of applying machine learning techniques to pediatric environmental health data, provide preliminary findings of epidemiologic risk estimates, and facilitate the development of future collaborative work strategies for our interdisciplinary research team.

Title: Hospital-Based Chemical Exposure and Neurodevelopmental Outcomes in Preterm Infants

PI: Dr. Annemarie Stroustrup

Each year in the United States, over 300,000 neonates require admission to a neonatal intensive care unit (NICU) where they are exposed to a chemical-intensive hospital environment. Preterm infants spend a particularly vulnerable developmental period corresponding to the third trimester in the NICU. It is known that chemical exposure at this point in development can permanently alter neurobehavioral outcomes in healthy fetuses, and that phthalates and phenols are common constituents of medical products used in neonatology. We also know that NICU graduates experience neurodevelopmental abnormalities at higher rates than the general population and may represent a highly vulnerable subpopulation for toxic chemical exposure. Neurodevelopmental disorders among NICU graduates are incompletely predicted by degree of prematurity or neonatal illness.