Grantee Research Project Results
2018 Progress Report: The Columbia Center for Childrens Environmental Health
EPA Grant Number: R836154Center: Southern California Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: The Columbia Center for Childrens Environmental Health
Investigators: Perera, Frederica P.
Current Investigators: Perera, Frederica P. , Rauh, Virginia , Rundle, Andrew , Peterson, Bradley S , Shepard, Peggy , Hernandez, Diana
Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2020)
Project Period Covered by this Report: September 1, 2017 through August 31,2018
Project Amount: $2,552,707
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Endocrine Disruptors , Human Health , Children's Health
Objective:
Project 1: Evaluate the Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
Aim 1: We will assess the effects of prenatal PAH exposure on neuropsychological performance at 15-17 years of age in a cohort of 350 adolescents who have been followed since the prenatal period.
Aim 2: We will assess the effects of prenatal PAH exposure on clinical outcomes at 15-17 years of age in the same adolescents.
Aim 3: We will examine the maturational trajectories of neuropsychological and clinical (cognitive, behavioral and emotional) development over time as a function of early PAH exposure.
Aim 4 (integrative): All 3 projects in this P50 share a common cohort in which we will explore how prenatal PAH exposure dysregulates neurodevelopment (project 1) and physical growth (project 2) via its mediational effects on the brain (project 3).
Project 2: Evaluate the Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue Mass in Adolescence: Linkages to Disrupted Self-Regulatory Processes
Aim 1: We will follow-up 350 CCCEH cohort children to ages 15 to 17 years old and measure abdominal subcutaneous adipose and visceral adipose tissue mass using MRI and fat mass index (FMI) using bio-impedance and anthropometric outcomes of height, weight, and waist circumference.
Aim 2: We will characterize growth and adiposity trajectories from childhood into adolescence.
Aim 3: We will apply cluster analysis to the anthropometric, eating behavior, physical activity and neurodevelopment and behavioral outcomes data collected at ages 15 to 17.
Aim 4 (integrative): All 3 projects in this P50 share a common cohort in which we will explore how prenatal PAH exposure dysregulates neurodevelopment (project 1) and physical growth (project_2) via its mediational effects on the brain (project 3).
Project 3: An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
Aim 1: We will assess the effects of prenatal and early childhood postnatal exposure to PAH (hereafter, ''early PAH exposure'') on the structure, function, and metabolism of self-regulatory systems (frontal, parietal, and mesial temporal cortices, and subcortical nuclei) in the brains of 350 cohort children who have undergone MRI scanning at 9-12 years of age.
Aim 2: We will assess whether PAH-related brain disturbances at 9-12 years of age (identified in Aim 1) mediate the association between prenatal PAH exposure and adverse Cognitive, Emotional, Behavioral, and Adiposity (hereafter, ''CEBA'') outcomes at 15-17 years.
Aim 3: We will acquire anatomical MRI scans at 15-17 years in 350 children with previous imaging at 9-12 years to assess how prenatal and early childhood exposures to PAH alter the trajectory of brain development throughout adolescence, and whether such alterations predict CEBA problems.
Aim 4 (integrative): All 3 projects in this P50 share a common cohort in which we will explore how prenatal PAH exposure dysregulates neurodevelopment (project 1) and physical growth (project 2) via its mediational effects on the brain (project 3).
Progress Summary:
Project 1: Evaluate the Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
In Year 3, we continued recruitment, scheduling, and assessment activities related to neuropsychological and clinical functioning in the adolescent subjects and their mothers. We continued to work closely with the Data Management Core (DMC) on methods for direct data entry, data security, and distributing data to study investigators. We monitored the protocol, using a checklist. We employed the decision rules from the protocol for detection of high-risk scores on psychosocial domains for: (1) immediate action or (2) mental health referral. Thus far, this procedure has been working smoothly. These objectives are consistent with Specific Aim 1, where we will assess the effects of prenatal PAH exposure on neuropsychological performance at 15- 17 years of age, and Specific Aim 2, where we will assess the effects of prenatal PAH exposure on clinical outcomes at 15-17 years of age in the same adolescents. In total, we have now completed 168 neuropsychological batteries and 179 MRI scans. No data final analyses or conclusions are available at this time.
In relation to Specific Aim 3, Dr. Amy Margolis, a co-investigator on this grant and our former Career Development Investigator (CDI), is exploring three research areas: 1) PAH exposure and academic achievement; 2) PAH exposure and Deficient Emotional Self-Regulation (DESR); and 3) ETS (+ PAH exposure) and DESR. It is important to note, however, that the DESR variable may not be the most robust construct. It was created using three Child Behaviour Check List (CBCL) scales for the assessment of self-regulation (attention, anxiety, and aggression). We are now considering use of other summary measures of dysregulation that can be derived from the data. Another manuscript on the attributable fraction of ADHD due to PAH is in preparation (by Drs. Perera and Herbstman).
Furthermore, the current CDI, Dr. David Pagliaccio, has been working with Drs. Rauh and Margolis to develop hypotheses for analyses and publication. David is interested in pursuing questions regarding anxiety, depression, allostatic load, and stressful experiences. His prior work has examined associations between internalizing pathology and brain function as well as effects of early life stress. Through these discussions, he has been interested in exploring how environmental exposures may moderate effects of early life adversity on emotional development and brain connectivity. He is currently finalizing a data request with Dr. Rauh, which specifies the hypothesis of his analysis, data required, and analytic plan.
For Specific Aim 4, extensive ongoing discussions and biostatistical consultations have been occurring among key study co-investigators in relation to the inclusion/exclusion of outliers and for the covariates to be used with the neuropsychological and imaging data analyses. This included assessment of the effects of PAH exposure outliers and confounders on the regression models linking prenatal PAH exposure to brain structure.
Project 2: Evaluate the Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue Mass in Adolescence: Linkages to Disrupted Self-Regulatory Processes
In our third year, we have been working to recruit and enroll study subjects who are aged 15 to 18 years. We have been beginning with participants who are the oldest and most likely to be entering college, the military or the workforce and then moving through the cohort to enroll the younger participants. We have been collecting data on physical activity, hedonic eating, food insecurity, height, weight, waist circumference, percent body fat, and blood pressure from the teens and their mothers. We have also been collecting data on weight cycling, weight loss practices and weight loss surgery from the mothers, as well as resting heart rate and heart rate recovery after a step test from the teens. Furthermore, the teens have been completing abdominal MRI scans, which measure visceral abdominal fat. These objectives are consistent with Specific Aims 1- 3.
For Specific Aim 1, we have begun preliminary analyses of the visceral and sub-cutaneous adipose tissue data derived from the MRI scans. Since we have only completed ~50% of the anticipated abdominal MRI scans for the project, these analyses are primarily aimed at understanding the distribution of the data, deciding whether transformations will need to be applied, concretizing the analysis strategy, identifying potential confounders, and establishing the analytical statistical code that will be employed in final analysis runs.
We have completed QC/QA assessments on all anthropometric data collected between ages 5 and 12 under prior funding. The prior NIEHS/EPA funded Children's Center projects collected anthropometric data from the children at ages 5, 7, 9, and 11, and also between ages 8.5 and 12; these have previously been treated as the canonical follow-up ages used in Center analyses. In total, height, weight, BMI, BMI z-score and BMI percentile data points were reviewed from 3,506 anthropometric measurements, 2,233 from the canonical follow-ups, and 1,273 from the sub-studies and pilot study databases that were merged into our main data set. This extensive review of all CCCEH datasets has allowed us to add 558 measures of height and weight to the trajectory analyses we plan for the P50 project, which is consistent with Specific Aim 2. To date, we have too few participants assessed at ages 15-18 years to conduct BMI z-score and FMI trajectory analysis of data from ages 5 to 18 years, but anticipating that in the next grant year, we will be poised to begin this analysis.
For Specific Aim 3, we have been processing the FELS Physical Activity Questionnaire data collected at ages 8.5 to 12 years, particularly identifying Metabolic Equivalent (MET) values for the variety of activities respondents reported on the FELS. The SAS code and MET values will support the processing of the FELS data being collected at ages 15-18 years. Also, we have been conducting preliminary analyses of trajectories of DESR scores derived from the Child Behavioral Check List (CBCL) using Group Based Latent Class analyses. Analyses of DESR score trajectory classes and dietary intake are nearing completion and thus far, we have not found any associations between DESR classes and dietary intake of protein, carbohydrates, total fats, sugar sweetened beverages, fruits or vegetables.
For Specific Aim 4, we collaborated with Drs. Peterson, Rauh, Perera and Goldsmith in developing and troubleshooting the statistical analysis strategy for analyzing associations between prenatal PAH exposures and brain structure at age 9-11. This included assessment of the effects of exposure outliers and confounders on the regression models linking prenatal PAH exposure to brain structure.
Project 3: An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
In Year 3, we focused on 4 main objectives: (1) Finalizing all processing of Magnetic Resonance Imaging (MRI) data for ages 9-12 years in our cohort (Specific Aims 1 and 2); (2) Integrating with the MRI dataset all of the demographic, behavioral, and cognitive data acquired at ages 9-12 years; (3) conducting statistical analyses for Specific Aims 1 and 2; (4) Processing anatomical brain imaging data as soon as possible after they are collected (Specific Aim 3). Consistent with Specific Aims 1 and 2, we have completed processing all of the MRI data for ages 9-12 years. This includes processing of anatomical MRI, task-based functional MRI (fMRI), Arterial Spin Labeling (ASL) perfusion, DRI, and Magnetic Resonance Spectroscopy (MRS) data. Integration with demographic, behavioral, and cognitive data with MRI measures is complete. Statistical analyses are well underway.
We have assessed the age and sex correlates of Diffusion Tensor Imaging (DTI) and MRS measures to identify the maturational changes in frontostriatal circuits in the peripubertal years, from ages 9-12 years. These circuits subserve the self-regulatory capacities that we are studying in this P50 grant. Identifying the normative maturation of these systems is necessary before studying the PAH-related alterations in that normal maturational trajectory.
For anatomical correlates of prenatal PAH exposure at ages 9-12 years, statistical analyses are underway for all the usable anatomical data collected at ages 9-12 years (N=316). We have worked intensively with our biostatistical colleagues (Drs. Goldsmith and Bowman) to develop the most rigorous multivariate statistical models possible for our anatomical measures. We have determined, for example, that our models are more stable when airborne PAH is log- transformed rather than untransformed, although the findings are very similar when using either of these forms of the variable. We have also assessed in detail the effects of various covariates (such as age, sex, maternal IQ, material hardship, ethnicity, and environmental stress) on the stability of our findings, concluding that our findings are extremely stable when including them or not. For DTI correlates of prenatal PAH exposure at ages 9-12 years, we correlated the total airborne prenatal PAH levels with FA (fractional anisotropy) and ADC (average diffusion coefficient, or mean diffusivity) values across the brain in 252 of our participants at ages 9-12. For MRS correlates of prenatal PAH exposure at ages 9-12 years, PAH correlates were similar for N-acetylaspartate (NAA), choline, and creatine.
In relation to Specific Aim 3, the quality of anatomical brain images acquired under the auspices of the P50 thus far is superb, both from the perspective of scanner performance and the presence of minimal motion artifact. Processing of the anatomical images is keeping pace with the rate of scan acquisition.
Future Activities:
Project 1: Evaluate the Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
In the next reporting period, we will continue to follow-up members of our cohort for intensive data collection as they reach ages 15-18 years. Study visits take place on weekdays and weekends, where participants will come to the Center's clinical offices to complete the neuropsychological testing and undergo anthropometric and fitness assessments, as well as have MRI scans completed at the Columbia University Neurological Institute. The recruitment and data collection procedures will continue to follow protocols that we originally stipulated in our grant application. The Data Management Core (DMC) has further established protocols for data acquisition, cleaning, storage and distribution to study investigators that will also ensure scientific rigor. We plan to continue to use DMC protocols. Also, Dr. Rauh and co-investigators will continue to work with the statistician, Dr. Bowman, on data analyses involving the integration of PAH exposure, behavioral, neuro-psychological and clinical data with MRI modalities.
Project 2: Evaluate the Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue Mass in Adolescence: Linkages to Disrupted Self-Regulatory Processes
In the next reporting period, we will continue to follow-up members of our cohort for intensive data collection as they reach ages 15-18 years. We expect study visits to take place on weekdays and weekends, when participants will come to the Center's clinical offices to complete the neuropsychological testing and undergo anthropometric and fitness assessments, as well as have MRI scans completed at the Columbia University Neurological Institute. The recruitment and data collection procedures will continue to follow the protocols that we originally stipulated in our grant application. The Data Management Core (DMC) has further established protocols for data acquisition, cleaning, storage and distribution to study investigators that will also ensure scientific rigor. Also, Dr. Rundle and co-investigators will continue to work with the statistician, Dr. Goldsmith, on all data analyses involving the integration of PAH exposure and child anthropometric variables with MRI brain imaging data collected at ages 9-11 years.
Project 3: An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
In the next reporting period, we will complete follow-up of the cohort members as they reach ages 15-18 years. Recruitment and data collection will follow the approaches described in our grant application. We will continue to process anatomical MRI data from each participant as they are collected. All anatomical data will be co-registered in a single template space and statistical analyses as described in the grant application for Specific Aims 3 and 4 will begin.
We also will complete mediation analysis for anatomical, DTI, MRS, and perfusion data. Findings will be interpreted and, based on those interpretations, manuscripts will be prepared and submitted for publication. Based on our findings thus far, we anticipate these findings to lead to publication in major scientific journals.
Journal Articles: 9 Displayed | Download in RIS Format
Other center views: | All 12 publications | 9 publications in selected types | All 9 journal articles |
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Conrad L, Rauh V, Hopener L, Acosta L, Perera F, Rundle A, Arteaga-Solis E, Miller R, Perzanowski M. Report of prenatal maternal demoralization and material hardship and infant rhinorrhea and watery eyes. Annals of Allergy Asthma & Immunology 2020;125(4):399. |
R836154 (2019) R832144 (Final) |
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Durham T, Guo J, Cowell W, Riley K, Wang S, Tang D, Perera F, Herbstman J. Prenatal PM2.5 Exposure in Relation to Maternal and Newborn Telomere Length at Delivery. Toxics 23;10(1):13. |
R836154 (Final) R827027 (2002) R832141 (Final) R834509 (Final) |
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Hoepner LA, Whyatt RM, Widen EM, Hassoun A, Oberfield SE, Mueller NT, Diaz D, Calafat AM, Perera FP, Rundle AG. Bisphenol A and adiposity in an inner-city birth cohort. Environmental Health Perspectives 2016;124(10):1644-1650. |
R836154 (2017) R834509 (Final) |
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Hopson MB, Margolis A, Rauh V, Herbstman JB. Impact of the home environment on the relationship between prenatal exposure to environmental tobacco smoke and child behavior. International Journal of Child Health and Human Development 2016;9(4):453-464. |
R836154 (2017) |
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Maresca MM, Hoepner LA, Hassoun A, Oberfield SE, Mooney SJ, Calafat AM, Ramirez J, Freyer G, Perera FP, Whyatt RM, Rundle AG. Prenatal exposure to phthalates and childhood body size in an urban cohort. Environmental Health Perspectives 2015 June 12 [Epub ahead of print], doi:10.1289/ehp.1408750. |
R836154 (2017) R834509 (2013) R834509C001 (Final) |
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Margolis AE, Herbstman JB, Davis KS, Thomas VK, Tang D, Wang Y, Wang S, Perera FP, Peterson BS, Rauh VA. Longitudinal effects of prenatal exposure to air pollutants on self-regulatory capacities and social competence. Journal of Child Psychology and Psychiatry 2016;57(7):851-860. |
R836154 (2017) R834509 (Final) |
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Perera FP, Wheelock K, Wang Y, Tang D, Margolis AE, Badia G, Cowell W, Miller RL, Rauh V, Wang S, Herbstman JB. Combined effects of prenatal exposure to polycyclic aromatic hydrocarbons and material hardship on child ADHD behavior problems. Environmental Research 2018;160:506-513. |
R836154 (2017) R836154 (2018) |
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Perera F, Nolte ELR, Wang Y, Margolis AE, Calafat AM, Wang S, Garcia W, Hoepner LA, Peterson BS, Rauh V, Herbstman J. Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10-12 years of age. Environmental Research 2016;151:195-202. |
R836154 (2017) |
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Widen EM, Whyatt RM, Hoepner LA, Mueller NT, Ramirez‐Carvey J, Oberfield SE, Hassoun A, Perera FP, Gallagher D, Rundle AG. Gestational weight gain and obesity, adiposity and body size in African-American and Dominican children in the Bronx and Northern Manhattan. Maternal & Child Nutrition 2016;12(4):918-928. |
R836154 (2017) R834509C001 (Final) |
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Supplemental Keywords:
Neurodevelopment, PAH, MRI, prenatal exposure, obesity, growth model, brain, adolescent outcomesRelevant Websites:
Columbia Center for Children's Environmental Health Exit
Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836154C001 The Impact of PAH Exposure on Adolescent Neurodevelopment: Disruption of Self-Regulatory Processes
R836154C002 The Impact of PAH Exposure on Childhood Growth Trajectories and Visceral Adipose Tissue
R836154C003 An MRI Study of the Effects of Prenatal and Early Childhood PAH Exposure on Brain Maturation and Its Mediating Influences on Adverse Adolescent Outcomes
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.