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Health Outcomes and Measures of the Environment (HOME) Study

Principal Investigator:
Lanphear, Bruce; Yolton, Kimberly; Cecil, Kim; Braun, Joseph; Chen, Aimin
Institution:
Cincinnati Children’s Hospital Medical Center
Location:
Cincinnati, Ohio
Number of Participants::
468 Mothers and 479 children
Brief Description::
This is a pregnancy and birth cohort study in Cincinnati to evaluate the impact of low-level fetal and childhood chemical exposures on health, developmental, and neurobehavioral outcomes. The study recruited over 400 pregnant women between 2003 to 2006. Offspring have been followed to age 12 years.
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Adulthood (mother); Youth (1-18 years)
Exposures:
Air Pollutants: Tobacco smoke
Brominated Compounds: Polybrominated diphenyl ethers (PBDEs)
Chlorinated Compounds: Polychlorinated biphenyls (PCBs)
Flame Retardants:
Fluorinated Compounds: Perfluoroalkyl substances (PFASs); Perfluorinated compounds (PFCs)
Metals: Lead; Mercury/methylmercury
Non-Chemical Stress: Built environment
Nutrition/Diet/Supplements: Vitamin D; Other Nutrition/Diet/Supplement
Personal Care/Consumer Products: Bisphenol A (BPA); Phthalates; Triclosan, Triclocarban
Pesticides: Not specified; Organophosphates; Pyrethroids
Health Outcomes:
Growth:
Immune Outcomes: Infection
Metabolic Outcomes: Obesity/body weight; Thyroid dysfunction
Musculoskeletal Outcomes: Bone density
Neurological/Cognitive Outcomes: Attention deficit hyperactivity disorder (ADHD); Neurobehavioral outcomes; Neurodevelopmental outcomes
Other Health Outcomes:
Respiratory Outcomes: Asthma
Biological Sample:
Blood; Breast milk; Cord blood; Hair; Saliva/buccal cells; Serum; Urine; Other Biological Sample

Related NIEHS-Funded Study Projects

Developmental Neurotoxicity of Organophosphate and Novel Brominated Flame Retardants in Children

Principal Investigator:
Chen, Aimin
Institution:
University of Cincinnati
Most Recent Award Year:
2019
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years, specifically at 1-12 years of age); Adulthood (mother, specifically 16 and 26 weeks of gestation and delivery)
Assessment: Youth (1-18 years, specifically at 12 years of age); Adulthood (mother)
Exposures:
Flame Retardants: Organophosphate flame retardants (OPFRs)
Novel brominated flame retardants:
Health Outcomes:
Metabolic Outcomes: Thyroid dysfunction
Neurological/Cognitive Outcomes: Attention deficit hyperactivity disorder (ADHD); Neurobehavioral outcomes; Neurodevelopmental outcomes
Biological Sample:
Cord blood; Serum (mother, child); Urine (mother, child)
Other Participant Data:
Repeated measures of child cognitive function, language skills, and memory function; child externalizing and internalizing behaviors, executive function including symptoms of ADHD; neuroimaging for brain anatomical structure, neurochemistry, organization of white matter tracts, and neural network connectivity; thyroid hormone levels from mother and child
Abstract:
Toxicological and epidemiologic studies have shown developmental neurotoxicity of polybrominated diphenyl ethers (PBDEs), a group of flame retardants (FRs) widely used in the U.S. and elsewhere. With the phase-out of PBDEs from the market since 2004, replacement FRs, including organophosphate flame retardants (OPFRs) and novel brominated flame retardants (NBFRs), are increasingly added to consumer products to meet flammability requirement. Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and Firemaster® 550 (FM 550) are the most commonly used replacement FRs. TDCPP, also referred to as ?chlorinated tris?, is an OPFR once added to children?s sleepwear in the 1970s but later removed because of toxicity concerns. Triphenylphosphate (TPP) and various TPP analogs are OPFR components in FM 550, while 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (TBB) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) are NBFR components in FM 550. TDCPP, TPP and FM 550 have been reported to alter thyroid hormone levels, reduce neuronal viability and replication, alter neuronal differentiation, cause abnormal embryogenesis and development, affect neurobehavior, and change gene expression levels and DNA methylation in experimental studies. Compared with experimental study evidence of OPFRs and NBFRs, there are significant gaps in our understanding of their developmental neurotoxicity in humans. We propose to examine developmental neurotoxicity of OPFRs and NBFRs using the Cincinnati-based Health Outcomes and Measures of the Environment (HOME) Study, an existing birth cohort of 410 children from prenatal to 12 years of age, with prenatal and postnatal exposure assessment, thyroid hormones, cognitive and behavioral tests, and neuroimaging data. We hypothesize that prenatal and postnatal exposures to OPFRs and NBFRs are associated with: 1) altered thyroid hormone levels in maternal, cord, and childhood serum samples; 2) decreased child cognitive function; 3) poorer child neurobehavioral functioning; and 4) adverse impact on brain structure, organization, and function identified by neuroimaging at age 12 years. The proposed research will be the first to comprehensively study developmental neurotoxicity of both OPFRs and NBFRs in children. Addressing neuroendocrinological, neurobehavioral, and neuroimaging aspects of brain development is highly innovative for this investigation. The findings will be of critical value to scientific community and policy makers evaluating potential impact of current-use replacement FRs on developing brain. The research is highly relevant to the National Institutes of Health mission to identify potential chemical exposures that disrupt brain development and provide critical data to inform prevention strategies.
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Early Life Phthalate and Perfluoroalkyl Substance Exposures and Childhood Bone Health

Principal Investigator:
Buckley, Jessie P
Institution:
Johns Hopkins University
Most Recent Award Year:
2019
Lifestage of Participants:
Exposure: Prenatal; Youth (1-18 years, specifically early childhood, mid childhood, early adolescence); Adulthood (mother)
Assessment: Infant (0-1 years, specifically at birth); Youth (1-18 years, specifically at 8 and 12 years of age)
Exposures:
Fluorinated Compounds: Perfluoroalkyl substances (PFASs)
Nutrition/Diet/Supplements: Vitamin D; Calcium
Personal Care/Consumer Products: Phthalates
Health Outcomes:
Growth: Skeletal growth
Musculoskeletal Outcomes: Bone density; Bone strength
Biological Sample:
Serum; Urine
Other Participant Data:
Skeletal development using growth curve modeling; bone density using dual-energy X-ray absorptiometry (in related study); height; vitamin D biomarker concentrations to asses vitamin D metabolism, calcium intake
Abstract:
Phthalates and perfluoroalkyl substances (PFAS) are synthetic chemicals with widespread human exposures that lower bone density in animals. Our preliminary data and limited epidemiologic studies report associations of these chemicals with shorter stature in children as well as lower bone density and altered vitamin D metabolism in adults. Low peak bone mass in adolescence is a strong modifiable risk factor for osteoporosis, a bone disease impacting millions of older Americans. Although early life is a critical period of skeletal growth and bone mass accrual, there are currently no longitudinal studies of phthalate or PFAS exposures in relation to childhood bone density. Therefore, our goal is to test the novel hypothesis that early life phthalate and PFAS exposures adversely impact skeletal growth, bone strength, and vitamin D metabolism in children. Our highly efficient proposal leverages the Health Outcomes and Measures of the Environment (HOME) Study, a prospective, racially-diverse pregnancy cohort study enrolled in Cincinnati, Ohio with existing exposure biomarker, confounder, and height measures from gestation through 8 years of age. Dual-energy X-ray absorptiometry measurements of bone density are currently being collected at an ongoing 12-year follow-up visit. We will additionally measure validated vitamin D and phthalate exposure biomarkers to investigate whether phthalate or PFAS exposures are associated with height trajectories from birth to age 12 years (Aim 1), bone density at age 12 years (Aim 2), and vitamin D biomarker concentrations at ages 8 and 12 years (Aim 3). Further, we will explore the role of chemical and nutritional co-exposures by examining whether height or bone density associations are modified or mediated by vitamin D biomarker concentrations or calcium intake (Aim 4). Using rich longitudinal data and a sophisticated Bayesian modeling approach, we will investigate potential windows of susceptibility (prenatal, early childhood, mid childhood, and early adolescence) as well as effects of cumulative exposures and exposure mixtures. This research will constitute the first systematic assessment of the role of phthalates and PFAS in altering bone health, a significant but understudied component of child well-being with critical importance for life-long risk of fractures and osteoporosis. In addition, this NIEHS ONES Award will support an exceptional Early Stage Investigator to establish an innovative research program specializing in children's environmental health. Finally, our findings will catalyze future research examining environmental impacts on bone health in later adolescence, elucidating biological mechanisms, investigating other environmental bone toxicants, and developing chemical or nutritional interventions with the goal of setting children on a path to healthier, stronger bones throughout life.
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Reproducibility and Robustness of Dimensionality Reduction

Principal Investigator:
Herring, Amy H
Institution:
Duke University
Most Recent Award Year:
2017
Exposures:
Health Outcomes:
Abstract:
In modern biomedical studies it has become commonplace to collect high-dimensional data, and hence dimensionality reduction tools are of critical importance and are routinely used. Some of the most common include clustering and factor analysis. The basic tenet behind dimensionality reduction is that we can replace a high dimensional set of variables by some low-dimensional summary. This is certainly necessary to make sense of complex data and also overcome problems with high-dimensional, low sample size data. However, a critical issue that has not been adequately studied is reproducibility. Standard approaches for dimension reduction can be very sensitive to choice of tuning parameters and arbitrary choices (e.g., choice of kernel or distance measure). This leads to a lack of robustness, with potentially very different results being produced when data are slightly perturbed. This lack of robustness tends to be compounded as the size of the data increases - both in terms of the sample size and number of variables collected. Also, a critical issue is lack of generalizability. In particular, dimensionality reduction for a particular group of individuals may fundamentally lack generalizability to other groups of individuals. This creates major problems in interpretation of results. Motivated in particular by environmental epidemiology studies collecting exposome data and by nutritional epidemiology, this project proposes to develop fundamentally new methods for improving robustness and reproducibility of dimensionality reduction through the following specific aims. (1) Develop robust methods of factor analysis designed to limit sensitivity to arbitrary assumptions and size of the data. (2) Develop robust methods of model-based clustering designed to limit sensitivity to arbitrary assumptions and size of the data. (3) Develop novel methods for robust clustering from multivariate and grouped data designed to avoid typical pitfalls of mixture models with increasing p. (4) Develop robust consensus methods that estimate low dimensional summaries that best reflect structure across subpopulations. (5) Apply the proposed methods to data from key epidemiologic cohorts that have measured a wide variety of environmental, behavioral, and biological exposures and provide a general use software package for implementation. This package is designed to be easily used and accommodate a broad variety of data types, further aiding reproducibility and transparency.
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Early Life Perfluoroalkyl Substance Exposure & Obesity: Mechanisms & Phenotyping

Principal Investigator:
Braun, Joseph M
Institution:
Brown University
Most Recent Award Year:
2016
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Fluorinated Compounds: Perfluoroalkyl substances (PFASs)
Health Outcomes:
Metabolic Outcomes: Obesity/body weight; DNA methylation
Biological Sample:
Blood; Cord blood; Hair; Urine
Other Participant Data:
Questionnaires; Cardiometabolic Risk Factors; Adipocytokines
Epigenetic Mechanisms Studied:
Peripheral blood leukocyte DNA methylation in cord blood and blood collected at 12 years of age
Abstract:
Childhood obesity is a major public health problem in the United States where nearly 17% of children are obese and another 15% are overweight. Emerging evidence suggests that early life exposure to chemical obesogens may increase the risk of obesity by affecting hormonal systems involved in adipogenesis, weight homeostasis, or metabolism. Perfluoroalkyl substances (PFAS) are a class of man-made chemicals used in stain/water repellant textiles, nonstick coatings, and food packaging. Growing evidence from animal, human, and experimental studies shows that these chemicals may be obesogens and affect cardio-metabolic endpoints as well. Despite this, there are few prospective human studies characterizing the obesogenic effects of PFAS, and even fewer investigating the molecular mechanisms of PFAS action. We will use the HOME Study, a prospective birth cohort of 375 women and their children from Cincinnati, OH to address these gaps and determine if PFAS exposures during three distinct periods of development are associated with body composition, cardio-metabolic risk markers, and relevant biological intermediates. Women in our study have serum PFOA concentrations two-times higher than US pregnant women due to their proximity to a fluoropolymer manufacturing plant, thus allowing us to examine the impact of high exposure to this chemical. We have measured serum concentrations of four PFAS (PFOA, PFOS, PFNA, and PFHxS) in pregnant women during the 2nd trimester and their children at 3 years of age. Concentrations will also be measured at 12 years of age. We will determine if higher exposures to these PFAS at these times in development are associated with: 1) Growth from birth to 12 years of age and state-of-the-art measures of body composition at 12 years of age; 2) Cardiometabolic risk factors, including central adiposity, blood pressure, and fasting lipid, glucose, and insulin levels at 12 years of age; 3) Cortisol concentrations in infant meconium and adiponectin or leptin levels in serum collected from neonates and 12 year olds; and 4), Changes in leukocyte DNA methylation at >485,000 loci in child blood samples collected at delivery and 12 years. These aims scale from the child to molecular level, allowing us to test the hypothesis that prenatal PFAS exposures adversely affect clinical endpoints in children across the first 12 years of life and related molecular pathways. By identifying potentially modifiable obesity risk factors using these data, we will provide critical data to scientists and policy makers about the health effects of PFAS exposures at three distinct life stages. These data may serve as a model for other potential chemical obesogens that have similar structures or act via comparable mechanisms. : Obesity is a growing threat to the health and well-being of children, and there is concern that early life environmental chemical exposures may cause obesity and related diseases. This project will use a study of pregnant women and their children to determine if pre- or postnatal perfluoroalkyl substance exposures are associated with child obesity, adverse cardio-metabolic markers, and changes in gene regulation. These results will help identify novel and modifiable obesity risk factors for childhood obesity.
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Internalizing Behaviors and Neuroimaging Outcomes: Impact of PBDE and PFC Exposures

Principal Investigator:
Yolton, Kimberly; Cecil, Kim
Institution:
Cincinnati Children's Hospital Medical Center
Most Recent Award Year:
2016
Lifestage of Participants:
Exposure: Prenatal; Youth (1-18 years, specifically at 3-5, 8, and 11-12 years of age); Adulthood (mother)
Assessment: Youth (1-18 years, specifically at 11-12 years of age)
Exposures:
Brominated Compounds: Polybrominated diphenyl ethers (PBDEs)
Fluorinated Compounds: Perfluorinated compounds (PFCs)
Health Outcomes:
Anxiety:
Mental Health Outcomes: Depression
Neurological/Cognitive Outcomes: Neurobehavioral outcomes; Neurodevelopmental outcomes
Biological Sample:
Serum; Urine
Other Participant Data:
Childhood symptoms of anxiety, depression, and social impairment; Neuroimaging to assess changes in anatomical structure, neurochemistry, organization of white matter tracts, and neural network connectivity
Abstract:
Human exposure to environmental contaminants is ubiquitous, and there is growing concern that exposure to some may be linked with the rise in neurobehavioral problems in children. Given the lack of conclusive evidence for many environmental toxicants, there is a critical need for well-designed longitudinal studies of prenatal and postnatal exposure with long-term follow-up to address focused questions about the impact of these chemicals, especially on neurobehavioral endpoints. We will study two chemical classes to which nearly all of the US population are exposed, polybrominated diphenyl ethers (PBDEs) and perfluorinated chemicals (PFCs), that have been used as flame retardants and surfactants, respectively. Among an established cohort of typically developing pre-adolescent children within the Health Outcomes and Measures of the Environment (HOME) Study, we will determine associations between prenatal and childhood exposure to these persistent pollutants and internalizing behaviors including anxiety, depression and social impairment. We will also obtain neuroimaging outcomes to examine associations with exposure. The HOME Study enrolled women during pregnancy and has thus far followed offspring until age 8y. We will extend follow-up to include a study visit at 11-12y to study associations in the pre-adolescent period. Prenatal exposures were measured using maternal pregnancy and newborn specimens with multiple childhood samples currently being analyzed. Over 97% of participating women had detectable levels of PBDEs and PFCs during pregnancy; comparable with nationally reported levels. We hypothesize that exposures to these chemicals subtly alter the brain to produce neurobehavioral deficits that will be evident in increased internalizing symptoms and adverse changes in anatomical structure, neurochemistry, organization of white matter tracts, and connectivity of neural networks. Aim 1: To determine the impact of prenatal and childhood exposures to PBDEs and PFCs on internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 2: To determine the impact of prenatal and childhood exposures to PBDEs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Exploratory aim (EA): To determine the impact of prenatal and childhood exposures to PFCs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Aim 3: To determine the potential mediational impact of brain structure, organization and function in the relationship between prenatal and childhood exposures to PBDEs and internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 4: To identify appropriate statistical methodologies to determine the association of single and multiple PBDE and PFC exposures with neurodevelopment across multiple developmental stages.
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Endocrine Disrupting Chemicals, Thyroid Hormones, and Child Neurobehavior

Principal Investigator:
Braun, Joseph M
Institution:
Brown University
Most Recent Award Year:
2015
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Personal Care/Consumer Products: Bisphenol A (BPA); Phthalates
Health Outcomes:
Metabolic Outcomes: Thyroid dysfunction
Neurological/Cognitive Outcomes: Attention deficit hyperactivity disorder (ADHD); Neurobehavioral outcomes; Neurodevelopmental outcomes
Biological Sample:
Blood (mother, child); Cord blood; Urine (mother, child); Meconium
Other Participant Data:
Behavioral/Cognitive tests
Genes or Other DNA Products Studied:
Thyroid stimulating hormone (TSH), T4, and triiodothyronine (T3)
Abstract:
Neurodevelopment is dependent on the action of thyroid hormones, and disruption of this hormonal axis during sensitive periods of development could increase the risk of clinical disorders like attention- deficit/hyperactivity disorder or learning disabilities. Phthalate, Triclosan, and bisphenol A (BPA) exposures are nearly universal in pregnant women and children, and could adversely affect thyroid hormones and brain development. No studies have prospectively linked these exposures to both thyroid hormones and neurodevelopment to determine if and when the developing fetal or child brain is more sensitive to these early life exposures. We will address this gap using an existing prospective cohort of 356 mother-child pairs who have been followed from the 2nd trimester of pregnancy until their child is ~8 years old. We will comprehensively assess pre- and postnatal phthalate, triclosan, and BPA exposure using infant meconium samples, two pregnancy urine samples, and up to six urine samples from infancy/childhood. Child cognitive abilities and behavior have been repeatedly assessed from 1-8 years of age and thyroid hormone levels will be measured during pregnancy, at birth, and 1, 3, 5, and ~8 years of age. These data will be systematically investigated to: 1) determine if and when early life phthalate, triclosan, and BPA exposures have an adverse effect on children's cognitive abilities and behavior between 1-8 years of age and 2) investigate the association between early life phthalate, triclosan, and BPA exposure and maternal/child thyroid hormone concentrations to determine if thyroid hormones mediate the associations between chemical exposures and neurobehavioral outcomes. Innovative features of this project include detailed prospective exposure assessment using meconium biomarkers to directly assess fetal exposure and up to 8 urine samples during gestation and childhood, repeated neurobehavioral assessments, hormonal intermediates that are essential for neurodevelopment and potentially sensitive to these chemical exposures, and sophisticated statistical methods to pinpoint the period of maximum sensitivity to these chemicals. These data will inform public health agencies about the toxicity of highly prevalent and potentially modifiable environmental chemical exposures and help target effective public health interventions aimed at reducing exposure during the most sensitive periods of brain development.
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Prenatal Sex Steroids, Bisphenol A, Phthalates, and Sexually Dimorphic Behaviors

Principal Investigator:
Braun, Joseph M
Institution:
Harvard University
Most Recent Award Year:
2013
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Personal Care/Consumer Products: Bisphenol A (BPA); Phthalates; Triclosan, Triclocarban
Health Outcomes:
Neurological/Cognitive Outcomes: Neurobehavioral outcomes
Biological Sample:
Urine (mother); Meconium
Other Participant Data:
Behavioral/Cognitive tests to assess childhood learning ability, spatial memory, working memory, and reference memory
Genes or Other DNA Products Studied:
Androgens and estrogens
Abstract:
The fetal brain is uniquely sensitive and environmental chemical exposures and dysregulation of the endocrine system may increase the risk of adverse neurobehavioral outcomes like autism, attention-deficit/hyperactivity disorder, or depression. Under the mentorship of Drs. Bellinger and Hauser, this training and research plan will build upon Dr. Braun's expertise as an environmental epidemiologist and prepare him for a career studying endocrine disrupting compounds (EDC) and their impact on hormonal systems and childhood neurodevelopment. Dr. Braun has never received formal training in these areas and few researchers possess this unique cross-disciplinary expertise. During the K99-phase of this award Dr. Braun will use tutorials, seminars/conferences, and didactic instruction to gain additional training in: 1) endocrinology concepts and the impact of environmental chemicals on the endocrine system; 2) psychometric test selection, administration, validation, and interpretation; and 3) childhood neurodevelopment. This training will be applied in an original research project where Dr. Braun will administer computerized tests of visuospatial ability to 25 children from Dr. Hauser's Environment and Reproductive Health (EARTH) study under the guidance of both Drs. Hauser and Bellinger. These computerized tests are analogues of the Morris Water Maze and Radial Arm Maze, which are used in animal studies of neurotoxicity. Using these new skills and the prospective Health Outcomes and Measures of the Environment (HOME) birth cohort, Dr. Braun will address two specific aims during the R00- phase of this award: 1) determine if gestational BPA/phthalate exposure is associated with visuospatial ability in 300 children and if sex modifies these associations and 2) determine if gestational BPA/phthalate exposure is associated with meconium sex steroid concentrations in 330 infants. Dr. Braun is well suited to carry out this research because of his prior training and the unique resources offered by his mentors, advisors, and institution. This proposed training and research will enable him to study the impact of EDCs on other hormonal systems and whether they increase the risk of adverse childhood behavioral outcomes. The examination of sex steroids will advance our knowledge of potential biological mechanisms of EDC action and the use of neurobehavioral tests with animal analogues will improve comparisons between epidemiological and animal studies. Public Health Relevance: Neurobehavioral disorders place an enormous burden on educational and medical resources; thus, priority is to understand factors associated with these disorders. The proposed studies could inform public health interventions by addressing important research gaps in our knowledge of BPA and phthalate neurotoxicity and its impact on human neurobehavior. Public Health Relevance: The fetus may be susceptible to endocrine disrupting compounds like bisphenol A (BPA) and phthalates. Exposure to these compounds may be detrimental to childhood neurodevelopment by disrupting gestational sex steroid metabolism. This application will use an integrated training plan in endocrine disruption and childhood neurodevelopment to prepare Dr. Joe M. Braun to produce high-quality research studying the impact of gestational BPA/phthalate exposures on fetal sex steroids and childhood visuospatial ability.
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Longitudinal Study of Exposure to PBDEs and PFCs and Child Neurobehavior

Principal Investigator:
Chen, Aimin (Contact); Lanphear, Bruce P; Yolton, Kimberly
Institution:
University of Cincinnati
Most Recent Award Year:
2011
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Brominated Compounds: Polybrominated diphenyl ethers (PBDEs)
Fluorinated Compounds: Perfluorinated compounds (PFCs); Perfluorooctanoic acid (PFOA); Perfluorooctanesulfonic acid (PFOS)
Health Outcomes:
Neurological/Cognitive Outcomes: Neurobehavioral outcomes; Neurodevelopmental outcomes
Biological Sample:
Blood; Breast milk; Serum
Environmental Sample:
House dust sample
Other Participant Data:
Thyroid hormones; Behavioral/Cognitive tests to assess cognition, learning and memory, motor skills, attention and executive function, and behavior
Abstract:
Polybrominated diphenyl ethers (PBDE) and perfluoroalkyl chemicals (PFCs, including perfluorooctane sulfonic acid [PFOS] and perfluorooctanoic acid [PFOA]) are persistent organic chemicals that were introduced several decades ago. Animal studies and limited human studies of PBDEs and PFCs have found evidence for developmental neurotoxicity in children, including thyroid hormone disruption, hyperactivity, delay in neuromotor maturation, and impaired cognition. Although these chemicals are being phased out, humans will still be exposed to PBDEs and PFCs in the environment for decades because these compounds were widely used as flame retardants and surfactants in consumer products. To address the potential adverse health risks of PBDEs and PFCs on fetal, infant, and child neurobehavioral development, the investigators will systematically examine their associations with thyroid function, cognition, learning and memory, motor skills, attention and executive function, and behavior from age 1 to 8 years. The long-term goal is to quantify the roles of PBDE and PFC exposures on child neurobehavior and to inform future prevention efforts. The three specific aims are to: 1) investigate the associations between prenatal and postnatal exposures to PBDEs and thyroid hormones and child neurobehavior; 2) examine the associations between prenatal and postnatal exposures to PFCs and thyroid hormones and child neurobehavior; and 3) assess the environmental exposure to PBDEs through transplacental and lactational routes and indoor dust in children. The investigators will test these associations in the Health Outcomes and Measures of the Environment (HOME) Study, an ongoing NIEHS-funded longitudinal birth cohort of 398 women and their children with current follow-up to 5 years. The investigators will extend the cohort to include an age 8 follow-up clinical visit with comprehensive neurobehavior assessments. The investigators will examine the PBDE and PFC exposures at different developmental stages (in utero at 16 weeks of gestation, ages 3, 5, and 8 years) and child neurobehavior measured at 1, 2, 3, 4, 5, and 8 years using stored serum samples. This longitudinal study will allow the investigators to determine the dose response, windows of susceptibility, and persistence of the association. We will also examine the contribution of PBDE exposures from house dust in a subset of children who have complete sample collection of maternal serum and child serum at 1, 2, and 3 years, along with extensive measures of mouthing behaviors. This research is closely related to the NIH mission to investigate prevalent environmental toxicants and children's neurodevelopment.
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Neurobehavioral Effects of Insecticides Exposure in Pregnancy and Early Childhood

Principal Investigator:
Yolton, Kimberly
Institution:
Cincinnati Children's Hospital Medical Center
Most Recent Award Year:
2009
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Pesticides: Organophosphates; Pyrethroids
Health Outcomes:
Neurological/Cognitive Outcomes: Attention deficit hyperactivity disorder (ADHD); Neurobehavioral outcomes
Biological Sample:
Blood; Cord blood; Urine (mother, child)
Other Participant Data:
Behavioral/Cognitive tests; Questionnaire
Genes or Other DNA Products Studied:
Maternal and child DNA
Epigenetic Mechanisms Studied:
Impact of PON1 on associations between pesticide exposure and health and neurobehavioral outcomes
Abstract:
The objective of this study is to examine the effects of exposure to prevalent insecticides on neurobehavioral outcomes in a cohort of 399 children. We will include an evaluation of prenatal exposure effects observed during the newborn period, as well as postnatal exposure effects through age six. Children are currently enrolled in cohort study investigating the health, developmental, and behavioral consequences of exposure to a variety of environmental toxicants and with planned follow-up to age two. Original funding was through NIEHS/EPA. Biological samples will be used to assess exposure to insecticides prenatally (maternal urine, infant meconium) and postnatally (child urine). We will examine newborn neurobehavioral outcomes within the first 36 hours of life and during a home visit at 4 weeks, using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS), to assess the earliest effects of prenatal exposure to prevalent insecticides. The study will extend follow-up of this cohort to include assessments or development, cognition, motor skills, and behaviors at ages 4, 5, and 6 in an effort to examine the effects of postnatal exposure to insecticides. Analyses will employ multivariate and causal modeling techniques. Potential covariates will include maternal drug and alcohol use during pregnancy, pregnancy outcomes and infant characteristics, maternal characteristics and qualities of the home environment, socioeconomic status variables, lead and tobacco exposure, and other variables as appropriate. Data from biological samples and neurobehavioral testing collected at earlier visits will also be available. We propose the following aims: AIM 1 To characterize the association of prenatal exposure to prevalent insecticides, as determined by biomarkers collected in maternal urine during pregnancy and in meconium shortly after birth, with neurobehavior during the newborn period measured with the NNNS. Aim 2 To characterize the association of postnatal exposure to prevalent insecticides, as determined by measures of insecticides in child urine with neurobehavior at ages four to six years. We will carefully examine the effects of prenatal and postnatal exposure to prevalent insecticides using multiple biological markers of exposure at numerous time points and sensitive neurobehavioral assessment tools from the newborn period through age five years. This study offers a unique opportunity to examine the early effects of prenatal and postnatal exposure to insecticides on neurobehavioral outcomes in a trajectory from the newborn period through age six years, while utilizing the research infrastructure of an established cohort study.
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Prenatal Low Level Tobacco & Phthalate Exposure & Childhood Respiratory Health

Principal Investigator:
Spanier, Adam J
Institution:
Pennsylvania State University
Most Recent Award Year:
2008
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Air Pollutants: Tobacco smoke
Personal Care/Consumer Products: Phthalates
Health Outcomes:
Respiratory Outcomes: Pulmonary inflammation; Asthma; Risk of wheeze; Respiratory infection
Biological Sample:
Cord blood; Hair; Serum; Urine; Meconium; Exhaled nitric oxide
Other Participant Data:
Questionnaire
Abstract:
Asthma and respiratory infection pose major burdens to child health. Prenatal tobacco exposure is a key risk factor for wheeze in young children, but there is little data about the relationship of prenatal low level exposures to tobacco (e.g. passive exposure of nonsmoking pregnant women) with risk of childhood wheeze or respiratory infection. There is emerging, yet limited evidence for novel environmental risk factors for wheeze such as phthalates. Advances in biomarkers offer an ability to quantify indicators of internal dose directly, reduce exposure misclassification, and enhance our ability to link exposures with disease. The primary objective for this K23 proposal is to rigorously characterize the relationship of common environmental exposures with risk of wheeze and respiratory infection in early childhood using serial biomarkers of exposure. The specific aims are to: 1) Test which measure of prenatal tobacco smoke exposure (different biomarkers, parent-report) is most strongly associated with risk of wheeze, respiratory infection, and pulmonary inflammation (fraction of exhaled nitric oxide, FeNO) in the first three years of life; 2) Investigate the association of low levels of maternal passive tobacco smoke exposure during pregnancy with risk of wheeze, respiratory infection, and pulmonary inflammation (FeNO) in children of nonsmoking mothers in the first three years of life; and 3) Investigate the association of prenatal phthalate exposure with risk of wheeze, respiratory infection, and pulmonary inflammation in the first three years of life. This proposal is novel because it uses serial biomarkers to measure individual exposure burden and low levels of exposure objectively throughout pregnancy and early childhood. Additionally, we will be the first to explore the role of prenatal phthalate exposure with the risk of childhood wheeze, respiratory infection, and pulmonary inflammation using biomarkers. Through this K23, the applicant will develop expertise in pediatric environmental epidemiology to position him to help broaden the model of environmental toxicology and respiratory epidemiology in children. It will also provide the background and training needed to develop an independent research career in clinical pediatrics and enhance our understanding of how environmental risk factors affect the development and exacerbation of pediatric asthma and respiratory disease and integrate this knowledge into prevention and treatment efforts.
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A Community-Based Trial to Prevent Lead Poisoning and Injuries

Principal Investigator:
Lanphear, Bruce; Yolton, Kimberly
Institution:
Cincinnati Children's Hospital Medical Center
Most Recent Award Year:
2007
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Metals: Lead
Non-Chemical Stress: Built environment
Health Outcomes:
Growth:
Neurological/Cognitive Outcomes: Attention deficit hyperactivity disorder (ADHD); Neurobehavioral outcomes; Neurodevelopmental outcomes
Other: Physical injury
Biological Sample:
Blood (mother, child); Breast milk; Cord blood; Hair; Saliva/buccal cells; Urine; Meconium; Vernix
Environmental Sample:
House dust sample; Drinking water sample; Soil sample
Other Participant Data:
Behavioral/Cognitive tests; Questionnaire
Abstract:
The contribution of residential hazards to children's health is poorly defined, but it is clear that some of the most prevalent disease and disabilities among U.S. children - including injuries and lead poisoning - would decline if such hazards were eliminated. Residential hazards also contribute to social disparities in children's health. This revised community-based participatory research application - a partnership of the Cincinnati Children's Hospital and the National Center for Healthy Housing - would extend the follow-up of an ongoing 402-person birth cohort (n=358 in the randomized trial) designed to test the efficacy of interventions to control residential hazards in children, from 2 years of age through 5 years. This extension is critical to fully evaluate the efficacy of reducing lead and injury hazards on children's intellectual abilities, behavioral problems and injuries during the peak vulnerability of early childhood. The central hypothesis of this application is that housing interventions will reduce the prevalence of lead toxicity and residential injuries in a racially diverse sample of children. The aims and hypotheses of this application are: 1.0 Determine the efficacy of lead hazard controls on children's blood lead levels and their risk for learning and behavioral problems. 1.1 Levels of lead in dust, soil and water will be significantly lower for housing units in the lead treatment arm compared with the injury control arm at 36, 48 and 60 month home visits. 1.2 Children who are assigned to the lead treatment arm will have lifetime blood lead levels that are >20% lower than children assigned to the injury treatment arm at 5 years. 1.3 Children in the lead treatment arm will have higher IQ scores at 5 years than children in the injury treatment arm. 1.4 Children in the lead treatment arm will have fewer behavioral problems at 5 years, especially measures related to ADHD, than children in the injury treatment arm. 1.5 Higher lead exposure, measured during pregnancy and early childhood using maternal blood, cord blood, meconium and children's blood, is inversely associated with IQ scores and directly associated with behavioral problems at 5 years in children with postnatal maximal blood lead levels < 5 /kg/dL 2.0 Determine the efficacy of comprehensive housing modifications on children's risk for injuries. 2.1 Children who are assigned to a multifactorial, housing intervention to prevent injuries will have 30% fewer unscheduled medical visits for housing injuries compared with children in the lead treatment arm. This is the first trial to test the efficacy of a multifactorial intervention for the primary prevention of two of the most prevalent causes of disease and disability in US children - lead toxicity and residential injuries. If efficacious, policy could be developed to reduce disease and disability linked with these hazards. It would also help resolve the ongoing controversy about the adverse consequences of low-level lead toxicity at blood lead levels previously thought to be safe. Our partnership with the National Center for Healthy Housing will enhance our ability to translate and disseminate the research results to affected communities locally and nationally.
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Study of Prevalent Neurotoxicants in Children

Principal Investigator:
Lanphear, Bruce
Institution:
Cincinnati Children's Hospital Medical Center
Most Recent Award Year:
2001
Lifestage of Participants:
Exposure: Prenatal; Infant (0-1 year); Youth (1-18 years); Adulthood (mother)
Assessment: Infant (0-1 year); Youth (1-18 years)
Exposures:
Air Pollutants: Tobacco smoke
Metals: Lead; Mercury/methylmercury
Pesticides: Not specified
Health Outcomes:
Growth:
Neurological/Cognitive Outcomes: Neurobehavioral outcomes
Other: Physical injury
Respiratory Outcomes: Asthma
Biological Sample:
Blood (mother, child); Breast milk; Cord blood; Hair; Saliva/buccal cells; Urine (mother, child); Meconium; Vernix
Environmental Sample:
House dust sample; Drinking water sample; Soil sample
Other Participant Data:
Behavioral/Cognitive tests; Surveys to assess environmental tobacco smoke exposure
Abstract:
Exposure to numerous environmental agents, including lead, mercury, PCBs, and environmental tobacco smoke, has been linked with adverse neurobehavioral effects. Still, the ideal biomarker for measuring in utero exposure to specific toxicants has not been established and the adverse effects of many potential neurotoxicants have not been rigorously tested. Fetal exposure is typically measured with self-reported surveys, maternal blood and urine, or cord blood. In contrast, meconium as a biomarker is a non-invasive method to simultaneously test for cumulative exposures to numerous toxicants. But it is unclear whether conventional biomarkers or meconium levels are more predictive of the adverse effects linked with specific toxicants. For lead exposure, emerging data indicate that our efforts should emphasize primary prevention, but the efficacy of lead hazard controls are uncertain, especially for children with low blood lead concentrations. The investigators propose to conduct a cohort study of 400 children, followed from less than 16 weeks gestation to 36 months of age, to examine the effect of low-level exposures to prevalent neurotoxicants. Endpoints include behavioral problems, such as conduct disorder and features consistent with ADHD, cognitive deficits, and hearing loss. The investigators will also conduct a nested, randomized controlled trial to test the efficacy of lead hazard controls on the development of adverse neurobehavioral effects. They will test the following hypotheses: 1) Children in the Lead Reduction Group will have blood lead levels that are 2.7 ug/dL (30%) or lower, significantly higher cognitive scores, less hearing loss, and fewer behavioral problems than one Control group at 36 months of age. 2) Fetal and postnatal exposures to pesticides, ETS and lead (at blood levels below 10 ug/dL) are associated with adverse neurobehavioral effects, growth delay and hearing loss in early childhood. 3) Fetal exposures, as measured by survey (ETS), maternal and cord blood (lead, methyl mercury, pesticides and ETS), and urine (pesticides), are less predictive of the adverse effects of toxicants on cognition, behavioral problems and hearing, compared with the same toxicants in meconium. This project, in combination with the research described in Project 2, will test the efficacy of an intervention for the primary prevention of lead toxicity, as measured by lead concentration and neurobehavioral functioning at 36 months of age, serve as a model to evaluate the adverse effects of exposures to multiple prevalent toxicants among fetuses and children test meconium levels as a biomarker of fetal exposure to numerous toxicants, and provide exposure and risk assessment data for residential pesticides.
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