2015 Progress Report: Children's Environmental Health & Disease Prevention Research Center at Dartmouth

EPA Grant Number: R835442
Center: Children's Environmental Health and Disease Prevention Center - Dartmouth College 2013
Center Director: Karagas, Margaret Rita
Title: Children's Environmental Health & Disease Prevention Research Center at Dartmouth
Investigators: Karagas, Margaret Rita , Enelow, Richard I. , Madan, Juliette , Nadeau, Kari
Current Investigators: Karagas, Margaret Rita
Institution: Dartmouth College , Stanford University
Current Institution: Dartmouth College
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: July 1, 2013 through June 30, 2018 (Extended to June 30, 2019)
Project Period Covered by this Report: July 1, 2014 through June 30,2015
Project Amount: $4,060,713
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

The Center’s core purpose is to identify and address key emerging issues related to health impacts of early life environmental exposures on children. There is a growing body of research connecting exposures early in life to a number of prevalent and life threatening diseases for children. Moreover, it is important to understand these exposures, as effects that begin to manifest in childhood may extend beyond into adult life. Significant gaps remain in our understanding of the effects of early life exposures and of potential treatments or measures to reduce harmful exposures, especially in utero or in early childhood. Thus, the overarching goal of this Center is to conduct research that enables risk assessors, regulators, policy makers, caregivers, and other stakeholders to increase their capacity to implement immediate and long-term strategies to prevent environmentally induced diseases associated with environmental exposures, such as arsenic in children.
 
Project 1: Childhood Immune Function and Exposure
The primary aims of this project are to test the hypothesis that in utero and early life arsenic (As) and other exposures are related to increased occurrence of childhood: 1) infections (number, type and severity of infections), in particular respiratory infections, in the first 5 years of life; 2) allergy and atopy in the first 5 years of life; and 3) diminished vaccine response (to Diphtheria/Tetanus/Pertussis, Pneumococcus and Polio) at age one. The secondary aim is to investigate the relation between in utero and early life arsenic (As) exposure on the development of the infant intestinal microbiome in the first year of life (based on stool samples taken at 6 weeks and 12 months of age). We hypothesize that As exposure will be associated with decreased diversity of the microbiome (e.g., based on the Simpson Diversity Index [SDI]), and differences in the relative abundance of specific phylotypes (e.g., bacterial genera and species) and/or predominant gene families or metabolic pathways.
 
Project 2: Water and Dietary Arsenic Exposure Related to Early Growth and Neurodevelopment
The project aims are to: 1) estimate As and other exposures from food and water ingestion and relate these intakes to biomarkers of exposure during the first 5 years of life, a period of rapidly changing diet for most children; 2) quantify the association of biomarkers of early life exposures with physical growth patterns during the first 5 years of life; and 3) quantify the association of biomarkers of early life exposures with neurodevelopment during the first 5 years of life.
 
Project 3: Placental Biomarkers of Exposure and Outcome
The project aims are to: 1) identify regions of variable DNA methylation in the placenta associated with in utero exposure to As by examining the methylation status of relevant candidate genes and regions using quantitative bisulfite pyrosequencing and using genome-wide DNA methylation arrays and biomarker-based exposure assessment; 2) identify altered gene expression in the placenta associated with in utero exposure to As by testing the expression of relevant candidate genes, including those identified in Aim 1, and their association with biomarker-based As exposure; and 3) examine if the As-associated variable DNA methylation and altered gene expression in placenta prospectively relates to child weight growth, infection, and neurodevelopmental outcomes.
 
Specific Objectives. This project is compelled by the hypothesis that environmental exposures encountered by a pregnant woman impact the gene expression of the infant’s placenta via epigenetic and other mechanisms and these functional alterations are associated with developmental outcomes in the children. Our objectives are to identify epigenetic and gene expression alterations in the placenta associated with maternal and infant biomarkers of in utero arsenic exposure, and to examine how these alterations are associated with critical health outcomes in the first few years of life. To accomplish these objectives, we are utilizing the existing and growing resources of the ongoing New Hampshire Birth Cohort Study, and are thus translating key findings from basic research into human populations.

Progress Summary:

Our well established and growing New Hampshire Birth Cohort Study (NHBCS) of maternal-infant dyads, continues to be of paramount importance to our research and Center. Building upon detailed exposure history, state-of-the-art biomarker measurements, and a rich collection of archived biospecimens obtained from this cohort, we are accelerating the pace of scientific advancement by leveraging additional Dartmouth resources, such as the Biorepository Core facility. Utilizing this state-of-the-art facility as an archiving and retrieval mechanism for our precious biological samples, greatly increases the rate at which we can obtain data, and publish our findings. Additionally, our Center has focused considerable attention over the last year on database creation and management, providing researchers and trainees web access to data descriptions, which again, is vastly accelerating our scientific productivity. This work will continue to be a focus in Year 3 of our Center. Researchers within our cohesive Center continue to contribute important scientific findings via national and international conferences and publications, and communicate them to key stakeholders to reduce environmental threats to children and improve their lifelong health.

Project 1Major Activities. Our project builds off the NHBCS, a longitudinal study of more than 1,000 maternal-infant pairs that has collected a wealth of data. These include: maternal health, diet and lifestyle factors, samples of household tap water, maternal blood, maternal urine and toenails (at 24-28 weeks gestation), cord blood and placenta, infant meconium, nails, urine and stool, and maternal toenails at 2 weeks postpartum. Additionally, we have conducted a structured review of prenatal, delivery, and delivery records. During the formative phase of our project, we began collecting more detailed information on maternal and newborn infections and allergies through a review of the medical records, and initiated an interval telephone interview for updated infection allergy/atopy information from the child’s caregiver over the first year of life. As part of our full Center’s project, after refining our protocols and study instruments, we continue this follow-up – both through a review of pediatric records in collaboration with Project 2, and the interval telephone interviews at 18, 24, 30, 36, 42, and 50 months. Through a R21 grant in collaboration with Dr. Kari Nadeau of the Berkeley/Stanford Children’s Center, we have conducted a pilot study to establish a protocol for collecting blood samples from our cohort members at one year of age to test for vaccine response. Another focus of our work is to investigate novel biomarkers of immune function and response. This includes microbiome analysis of infant stool samples beginning at birth and through the first year of life. During the project period, we developed and implemented standard operating procedures for data collection, laboratory operation, quality assurance procedures, and key aspects of the project research.

Specific Objectives. Infectious diseases remain the leading cause of illness in children in the United States, and of mortality in children worldwide. Additionally, the prevalence of allergy and atopic diseases have become more widespread among children in recent years, for reasons that are not fully understood. Therefore, our objectives are to assess the relation of environmentally relevant levels of As (and other exposures) with clinical and biologic measures of early childhood immune function (e.g., infection/allergy/atopy, vaccine response and intestinal microbial acquisition). To achieve our objectives, we are leveraging an ongoing U.S. prospective study of women and infants enrolled during pregnancy who are residents of New Hampshire and who obtain household water from private wells, a potential source of arsenic exposure in the region. Understanding whether common levels of exposure during the vulnerable periods of fetal development and early childhood impact immune response has widespread implications for public health and practice change. 

Significant Findings. In mechanistic studies with Dr. Nadeau of the Berkeley/Stanford Children’s Center and Dr. David Robbins (Project 3), we now have published our phenotype data from umbilical cord blood samples, which indicated a reduced number of fetal T cells (which in turn could enhance risk of infection, and diminish vaccine response), and an increased number of inactivated Th2 cells (which could lead to increased risk of allergy/atopy) (Nadeau, et al., 2014). In placenta, increased expression of the proinflammatory cytokine IL1B was related to increased expression of an arsenite transporter gene (Nadeau, et al., 2014). By collaborating with Project 2 on arsenic in breast milk, formula, and early life diet (Carignan, et al., 2015), we will be able to characterize windows of exposure and their impact on microbiome development over the first year of life and infant risk of infection early in life.

Key Outcomes and Other Achievements.  We continue to grow Project 1 as part of the Dartmouth Center, building on work we began in our formative Center and our R21 with Dr. Kari Nadeau at Stanford. Through this project, we are rigorously following children from our cohort to determine their risk of infection, allergy and atopy.  In collaboration with Project 2, we are collecting detailed information not only on in utero exposures but exposures monitored through dietary sources, questionnaires, and biomarkers taken on infants and children. Additionally, we have initiated new components of the study to measure infant’s vaccine response and the developing microbiome, and continue to make steady strides on these components in Year 2 of our grant. Several ancillary studies are newly underway and include collaborations with other children’s centers and institutions. Likewise, a number of collaborative grants have been submitted in the past year.

Project 2: Assessment of dietary exposure to arsenic during the first year of life has continued using the approaches developed during the formative P20 grant phase, diet assessment at age 3 is underway, and diet assessment at age 5 will begin soon. We have created a medical record review protocol and web-based medical record review interface using the REDCap application. We are conducting medical record reviews to abstract physical growth data. In addition to growth assessments, we are performing neurodevelopmental assessments using mailed standardized behavioral assessments at age 3, and will obtain more detailed in-person assessments at age 5 years. Given growing public health concern regarding the increasing prevalence of Autism spectrum disorders and the potential for developmental neurotoxicants to play a role, we refined our neurobehavioral assessment protocols to include a standardized instrument for eliciting parental report of autism-related behaviors (the Social Responsive Scale or SRS).

Project 3: Major Activities. In the original project application, we proposed to examine a panel of candidate genes for their DNA methylation status and for their expression, and we have worked to design, validate, and implement pyrosequencing assays and a nanostring panel for a number of these genes. We now have begun assays on the selected samples from the New Hampshire cohort, and have begun to undertake analyses of the data obtained from these assays. We will continue to perform assays and analyses moving forward.

Significant Findings. We performed and published on an EWAS examining the association of mercury exposure assessed as maternal toenail mercury and cord blood DNA methylation, and the interaction between mercury and arsenic exposure on cord blood DNA methylation. This analysis was undertaken as a collaboration with Project 3 and Dr. Karagas in Project 1, as well as Dr. Molly Kile of Oregon State University, and her PhD student Andres Cardenas, who received a KC Donnelly Externship to work with us on these analyses. We identified a decrease in the estimated cord blood monocyte proportion (β=-2.5; 95% CI: -5.0, -1.0), and an increase in cord blood B-cell proportion only for female infants (β=-3.5%; 95% CI: 1.0, 7.0) associated with maternal toenail mercury levels. Among the top 100 differentially methylated CpGs for the interaction between arsenic and mercury, there was a greater than expected proportion of loci located in CpG islands (P=0.045) and in South shore regions (P=0.009) and all of these loci were hypermethylated.

Key Outcomes and Other Achievements. As noted above, a number of manuscripts have been published or are being prepared for peer review detailing this work, and analyses are continuing. Dr. Marsit served as chair of a session entitled Epigenetic Effects of Early Life Environmental Exposures and presented on work linking mercury exposure to epigenetic alterations and neurobehavior at the International Society for Environmental Epidemiology meeting in August 2014.  Dr. Marsit also was an invited presenter at the Prenatal Programming and Toxicity (PPTOX IV) meeting in Boston in October 2014, where he presented on the importance of considering imprinting in the placenta related to environmental stressors. He also has presented on the EPA Children’s Center’s monthly webinars in April and May, speaking on epigenetics and the importance of the placenta in children’s environmental health, and was invited to present in May at the University of Kentucky’s Superfund Research Program Seminar Series and the University of Southern California’s NIEHS/EPA Children’s Environmental Health Center on his placental work. Dr. Robbins recently presented some of this work at the Université de Geneve and the Université de Nice.

Future Activities:

Project 1: Our focus over the coming grant period will be to continue to obtain follow-up data through interval interviews and medical record reviews. We will enhance collection of 1 year blood samples by including additional pediatric practices to perform laboratory analyses of vaccine response, and obtain repeated stool samples for microbiome analyses. One-year plasma samples will be sent in batches to Stanford University to test for antibody response to tetanus and diphtheria toxoid, pertussis, pneumococcus, and polio vaccine. We will strive to continue to engage early career investigators and trainees in our research. We plan to present our research findings at scientific conferences, publish our initial findings in the scientific literature, and work toward disseminating our findings to relevant communities to implement practice change. We will continue to work with our COTC to design interventions to encourage private well testing and to understand the barriers to remediation of arsenic contamination in private drinking water supplies. We also will work with our COTC, as well as collaboratively with other Children’s Centers, FDA and other agencies, around issues regarding arsenic in rice and other childhood exposures that may pose short- or long-term health impacts.

Project 2: In the coming year, we will continue our dietary assessments and urinary and toenail biomarker collection. We also will continue reviewing pediatric records e.g., for anthropometric data. In addition, we will continue to obtain 3-year neurodevelopmental evaluations and dietary information, and begin performing the 5-year in-person evaluations of neurodevelopment and anthropometry and collections of data on dietary intake and urinary biomarkers of exposure.

Project 3: The research team of Drs. Marsit and Robbins has made tremendous progress in moving the analyses forward. Dr. Marsit’s team now is continuing the analyses obtained from the genomewide assessments and that team also will begin to undertake the repetitive element candidate gene investigations using the data that now are all in hand. Dr. Robbins is in the process of expanding the gene expression profiling of candidate genes to an additional subset of the birth cohort. Further, he is examining how arsenic speciation might contribute to some of the sexually dimorphic responses noted above. The research team is on track to complete the goals and objectives as outlined in the grant proposal.


Journal Articles: 92 Displayed | Download in RIS Format

Other center views: All 144 publications 92 publications in selected types All 92 journal articles
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Journal Article Appleton AA, Lester BM, Armstrong DA, Lesseur C, Marsit CJ. Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior. Psychoneuroendocrinology 2015;52:32-42. R835442 (2015)
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  • Journal Article Armstrong DA, Lesseur C, Conradt E, Lester BM, Marsit CJ. Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research. FASEB Journal 2014;28(5):2088-2097. R835442 (2014)
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  • Journal Article Armstrong DA, Green BB, Blair BA, Guerin DJ, Litzky JF, Chavan NR, Pearson KJ, Marsit CJ. Maternal smoking during pregnancy is associated with mitochondrial DNA methylation. Environmental Epigenetics 2016;2(3):dvw020. R835442 (2017)
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  • Journal Article Banister CE, Koestler DC, Maccani MA, Padbury JF, Houseman EA, Marsit CJ. Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas. Epigenetics 2011;6(7):920-927. R835442 (2014)
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  • Journal Article Beane Freeman LE, Karagas MR, Baris D, Schwenn M, Johnson AT, Colt JS, Jackson B, Hosain GM, Cantor KP, Silverman DT. Is the inverse association between selenium and bladder cancer due to confounding by smoking? American Journal of Epidemiology 2015;181(7):488-495. R835442 (2015)
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  • Journal Article Bommarito PA, Martin E, Smeester L, Palys T, Baker ER, Karagas MR, Fry RC. Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire. Reproductive Toxicology 2017;73:184-195. R835442 (2018)
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  • Journal Article Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. R835442 (2017)
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  • Journal Article Caito SW, Jackson BP, Punshon T, Scrimale T, Grier A, Gill SR, Love TM, Watson GE, van Wijngaarden E, Rand MD. Editor's Highlight: Variation in methylmercury metabolism and elimination status in humans following fish consumption. Toxicological Sciences 2018;161(2):443-453. R835442 (2018)
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  • Journal Article Cardenas A, Koestler DC, Houseman EA, Jackson BP, Kile ML, Karagas MR, Marsit CJ. Differential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero. Epigenetics 2015;10(6):508-515. R835442 (2015)
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  • Journal Article Carignan CC, Cottingham KL, Jackson BP, Farzan SF, Gandolfi AJ, Punshon T, Folt CL, Karagas MR. Estimated exposure to arsenic in breastfed and formula-fed infants in a United States cohort. Environmental Health Perspectives 2015;123(5):500-506. R835442 (2015)
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  • Journal Article Chen Y, Karagas MR. Arsenic and cardiovascular disease: new evidence from the United States. Annals of Internal Medicine 2013;159(10):713-714. R835442 (2014)
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  • Journal Article Chernikova DA, Koestler DC, Hoen AG, Housman ML, Hibberd PL, Moore JH, Morrison HG, Sogin ML, Zain-Ul-Abideen M, Madan JC. Fetal exposures and perinatal influences on the stool microbiota of premature infants. Journal of Maternal-Fetal and Neonatal Medicine 2016;29(1):99-105. R835442 (2017)
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  • Journal Article Chernikova DA, Madan JC, Housman ML, Zain-Ul-Abideen M, Lundgren SN, Morrison HG, Sogin ML, Williams SM, Moore JH, Karagas MR, Hoen AG. The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth. Pediatric Research 2018;84(1):71-79. R835442 (2018)
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  • Journal Article Cottingham KL, Karimi R, Gruber JF, Zens MS, Sayarath V, Folt CL, Punshon T, Morris JS, Karagas MR. Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water. Nutrition Journal 2013;12:149. R835442 (2014)
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  • Journal Article Davis MA, Gilbert-Diamond D, Karagas MR, Li Z, Moore JH, Williams SM, Frost HR. A dietary-wide association study (DWAS) of environmental metal exposure in US children and adults. PLoS One 2014;9(9):e104768. R835442 (2015)
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  • Journal Article Davis MA, Li Z, Gilbert-Diamond D, Mackenzie TA, Cottingham KL, Jackson BP, Lee JS, Baker ER, Marsit CJ, Karagas MR. Infant toenails as a biomarker of in utero arsenic exposure. Journal of Exposure Science & Environmental Epidemiology 2014;24(5):467-473. R835442 (2015)
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  • Journal Article Davis MA, Higgins J, Li Z, Gilbert-Diamond D, Baker ER, Das A, Karagas MR. Preliminary analysis of in utero low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports. Environmental Health 2015;14:12 (11 pp.). R835442 (2015)
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  • Journal Article Davis MA, Signes-Pastor AJ, Argos M, Slaughter F, Pendergrast C, Punshon T, Gossai A, Ahsan H, Karagas MR. Assessment of human dietary exposure to arsenic through rice. Science of the Total Environment 2017;586:1237-1244. R835442 (2017)
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  • Journal Article Demidenko E. Exact and approximate statistical inference for nonlinear regression and the estimating equation approach. Scandinavian Journal of Statistics 2017;44(3):636-665. R835442 (2018)
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  • Journal Article Emond JA, Gilbert-Diamond D, Tanski SE, Sargent JD. Energy drink consumption and the risk of alcohol use disorder among a national sample of adolescents and young adults. Journal of Pediatrics 2014;165(6):1194-1200. R835442 (2015)
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  • Journal Article Emond JA, Sargent JD, Gilbert-Diamond D. Patterns of energy drink advertising over US television networks. Journal of Nutrition Education and Behavior 2015;47(2):120-126.e1. R835442 (2015)
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  • Journal Article Emond JA, Karagas MR, Baker ER, Gilbert-Diamond D. Better diet quality during pregnancy is associated with a reduced likelihood of an infant born small for gestational age: an analysis of the Prospective New Hampshire Birth Cohort Study. Journal of Nutrition 2018;148(1):22-30. R835442 (2018)
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  • Journal Article Everson TM, Kappil M, Hao K, Jackson BP, Punshon T, Karagas MR, Chen J, Marsit CJ. Maternal exposure to selenium and cadmium, fetal growth, and placental expression of steroidogenic and apoptotic genes. Environmental Research 2017;158:233-244. R835442 (2017)
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  • Journal Article Everson TM, Punshon T, Jackson BP, Hao K, Lambertini L, Chen J, Karagas MR, Marsit CJ. Cadmium-associated differential methylation throughout the placental genome:epigenome-wide association study of two U.S. birth cohorts. Environmental Health Perspectives 2018;126(1):017010 (13 pp.). R835442 (2018)
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  • Journal Article Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environmental Health Perspectives 2015;123(10):999-1006. R835442 (2015)
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  • Journal Article Farzan SF, Chen Y, Rees JR, Zens MS, Karagas MR. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study. Toxicology and Applied Pharmacology 2015;287(2):93-97. R835442 (2015)
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  • Journal Article Farzan SF, Brickley EB, Li Z, Gilbert-Diamond D, Gossai A, Chen Y, Howe CG, Palys T, Karagas MR. Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort. Environmental Research 2017;156:426-433. R835442 (2017)
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  • Journal Article Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, Gosse JA, Marsit CJ, Karagas MR, Robbins DJ. Association between In Utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environmental Health 2013;12:58 (8 pp.). R835442 (2014)
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  • Journal Article Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almqvist C, Annesi-Maesano I, Arshad H, Baiz N, Bakermans-Kranenburg MJ, Bakulski KM, Binder EB, Bouchard L, Breton CV, Brunekreef B, Brunst KJ, Burchard EG, Bustamante M, Chatzi L, Cheng Munthe-Kaas M, Corpeleijn E, Czamara D, Dabelea D, Davey Smith G, De Boever P, Duijts L, Dwyer T, Eng C, Eskenazi B, Everson TM, Falahi F, Fallin MD, Farchi S, Fernandez MF, Gao L, Gaunt TR, Ghantous A, Gillman MW, Gonseth S, Grote V, Gruzieva O, Haberg SE. Cohort profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. International Journal of Epidemiology 2018;47(1):22-23u. R835442 (2018)
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  • Journal Article Frediani JK, Naioti EA, Vos MB, Figueroa J, Marsit CJ, Welsh JA. Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005-2014. Environmental Health 2018;17(1):6 (8 pp.). R835442 (2018)
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  • Journal Article Gilbert-Diamond D, Li Z, Adachi-Mejia AM, McClure AC, Sargent JD. Association of a television in the bedroom with increased adiposity gain in a nationally representative sample of children and adolescents. JAMA Pediatrics 2014;168(5):427-434. R835442 (2014)
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  • Journal Article Gossai A, Lesseur C, Farzan S, Marsit C, Karagas MR, Gilbert-Diamond D. Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort. Environmental Research 2015;136:180-186. R835442 (2015)
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  • Journal Article Grandjean P, Barouki R, Bellinger DC, Casteleyn L, Chadwick LH, Cordier S, Etzel RA, Gray KA, Ha EH, Junien C, Karagas M, Kawamoto T, Paige Lawrence B, Perera FP, Prins GS, Puga A, Rosenfeld CS, Sherr DH, Sly PD, Suk W, Sun Q, Toppari J, van den Hazel P, Walker CL, Heindel JJ. Endocrinology 2015;156(10):3408-3415. R835442 (2017)
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  • Journal Article Green BB, Armstrong DA, Lesseur C, Paquette AG, Guerin DJ, Kwan LE, Marsit CJ. The role of placental 11-beta hydroxysteroid dehydrogenase type 1 and type 2 methylation on gene expression and infant birth weight. Biology of Reproduction 2015;92(6):149 (8 pp.). R835442 (2015)
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  • Journal Article He X, Karagas R, Murray C. Impact of receipt of private well arsenic test results on maternal use of contaminated drinking water in a U.S. population. Science of the Total Environment 2018;643:1055-1012. R835442 (2018)
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  • Journal Article Hoen AG, Li J, Moulton LA, O'Toole GA, Housman ML, Koestler DC, Guill MF, Moore JH, Hibberd PL, Morrison HG, Sogin ML, Karagas MR, Madan JC. Associations between gut microbial colonization in early life and respiratory outcomes in cystic fibrosis. Journal of Pediatrics 2015;167(1):138-147.e1-3. R835442 (2015)
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  • Journal Article Hoen AG, Madan JC, Li Z, Coker M, Lundgren SN, Morrison HG, Palys T, Jackson BP, Sogin ML, Cottingham KL, Karagas MR. Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population. Scientific Reports 2018;8(1):12627 (10 pp.). R835442 (2018)
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  • Journal Article Houseman EA, Kelsey KT, Wiencke JK, Marsit CJ. Cell-composition effects in the analysis of DNA methylation array data:a mathematical perspective. BMC Bioinformatics 2015;16(1):95 (16 pp.). R835442 (2016)
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  • Journal Article Jackson BP. Fast ion chromatography-ICP-QQQ for arsenic speciation. Journal of Analytical Atomic Spectrometry 2015;30(6):1405-1407. R835442 (2015)
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  • Journal Article Jackson BP, Punshon T. Recent advances in the measurement of arsenic, cadmium, and mercury in rice and other foods. Current Environmental Health Reports 2015;2(1):15-24. R835442 (2015)
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  • Journal Article Jackson BP, Liba A, Nelson J. Advantages of reaction cell ICP-MS on doubly charged interferences for arsenic and selenium analysis in foods. Journal of Analytical Atomic Spectrometry 2015;30(5):1179-1183. R835442 (2015)
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  • Journal Article Karagas MR, Zens MS, Li Z, Stukel TA, Perry AE, Gilbert-Diamond D, Sayarath V, Stephenson RS, Barton D, Nelson HH, Spencer SK. Early-onset basal cell carcinoma and indoor tanning: a population-based study. Pediatrics 2014;134(1):e4-e12. R835442 (2015)
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  • Journal Article Karagas MR, Gossai A, Pierce B, Ahsan H. Drinking water arsenic contamination, skin lesions and malignancies: a systematic review of the global evidence. Current Environmental Health Reports 2015;2(1):52-68. R835442 (2015)
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  • Journal Article Kaushal A, Zhang H, Karmaus WJJ, Everson TM, Marsit CJ, Karagas MR, Tsai SF, Wen HJ, Wang SL. Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life. Environmental Health 2017;16(1):50. R835442 (2017)
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  • Journal Article Kingsley SL, Deyssenroth MA, Kelsey KT, Awad YA, Kloog I, Schwartz JD, Lambertini L, Chen J, Marsit CJ, Wellenius GA. Maternal residential air pollution and placental imprinted gene expression. Environment International 2017;108:204-211. R835442 (2018)
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  • Journal Article Koestler DC, Avissar-Whiting M, Houseman EA, Karagas MR, Marsit CJ. Differential DNA methylation in umbilical cord blood of infants exposed to low levels of arsenic in utero. Environmental Health Perspectives 2013;121(8):971-977. R835442 (2014)
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  • Journal Article Lansigan RK, Emond JA, Gilbert-Diamond D. Understanding eating in the absence of hunger among young children: a systematic review of existing studies. Appetite 2015;85:36-47. R835442 (2015)
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  • Journal Article Lesseur C, Armstrong DA, Murphy MA, Appleton AA, Koestler DC, Paquette AG, Lester BM, Marsit CJ. Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior. Psychoneuroendocrinology 2014;40:1-9. R835442 (2014)
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  • Journal Article Lesseur C, Paquette AG, Marsit CJ. Epigenetic regulation of infant neurobehavioral outcomes. Medical Epigenetics 2014;2(2):71-79. R835442 (2015)
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  • Journal Article Lester BM, Marsit CJ. Epigenetic mechanisms in the placenta related to infant neurodevelopment. Epigenomics 2018;10(3):321-333. R835442 (2018)
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  • Journal Article Li Z, Frost HR, Tosteson TD, Zhao L, Liu L, Lyons K, Chen H, Cole B, Currow D, Bakitas M. A semiparametric joint model for terminal trend of quality of life and survival in palliative care research. Statistics in Medicine 2017;36(29):4692-4704. R835442 (2018)
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  • Journal Article Litzky JF, Boulet SL, Esfandiari N, Zhang Y, Kissin DM, Theiler RN, Marsit CJ. Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants. American Journal of Obstetrics Gynecology 2018;218(4):433.e1-433.e10. R835442 (2018)
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  • Journal Article Litzky JF, Boulet SL, Esfandiari N, Zhang Y, Kissin DM, Theiler RN, Marsit CJ. Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry study. Journal of Assisted Reproduction and Genetics 2018;35(6):1027-1037. R835442 (2018)
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  • Journal Article Litzky JF, Deyssenroth MA, Everson TM, Lester BM, Lambertini L, Chen J, Marsit CJ. Prenatal exposure to maternal depression and anxiety on imprinted gene expression in placenta and infant neurodevelopment and growth. Pediatric Research 2018;83(5):1075-1083. R835442 (2018)
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  • Journal Article Lundgren SN, Madan JC, Emond JA, Morrison HG, Christensen BC, Karagas MR, Hoen AG. Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner. Microbiome 2018;6(1):109(11 pp.). R835442 (2018)
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  • Journal Article Maccani JZ, Koestler DC, Houseman EA, Marsit CJ, Kelsey KT. Placental DNA methylation alterations associated with maternal tobacco smoking at the RUNX3 gene are also associated with gestational age. Epigenomics 2013;5(6):619-630. R835442 (2014)
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  • Journal Article Maccani JZ, Koestler DC, Houseman EA, Armstrong DA, Marsit CJ, Kelsey KT. DNA methylation changes in the placenta are associated with fetal manganese exposure. Reproductive Toxicology 2015;57:43-49. R835442 (2016)
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  • Journal Article Maccani JZJ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ. Placental DNA methylation related to both infant toenail mercury and adverse neurobehavioral outcomes. Environmental Health Perspectives 2015;123(7):723-729. R835442 (2015)
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  • Journal Article Marsit CJ, Brummel SS, Kacanek D, Seage III GR, Spector SA, Armstrong DA, Lester BM, Rich K, Pediatric HIV/AIDS Cohort Studies Network. Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero. Epigenetics 2015;10(8):708-716. R835442 (2015)
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  • Journal Article Marsit CJ. Influence of environmental exposure on human epigenetic regulation. Journal of Experimental Biology 2015;218(Pt 1):71-79. R835442 (2015)
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  • Journal Article Marsit CJ. Placental epigenetics in children’s environmental health. Seminars in Reproductive Medicine 2016;34(1):36-41. R835442 (2016)
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  • Journal Article Martin E, Smeester L, Bommarito PA, Grace MR, Boggess K, Kuban K, Karagas MR, Marsit CJ, O'Shea TM, Fry RC. Sexual epigenetic dimorphism in the human placenta:implications for susceptibility during the prenatal period. Epigenomics 2017;9(3):267-278. R835442 (2017)
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  • Journal Article Nachman KE, Punshon T, Rardin L, Signes-Pastor AJ, Murray CJ, Jackson BP, Guerinot ML, Burke TA, Chen CY, Ahsan H, Argos M, Cottingham KL, Cubadda F, Ginsberg GL, Goodale BC, Kurzius-Spencer M, Meharg AA, Miller MD, Nigra AE, Pendergrast CB, Raab A, Reimer K, Scheckel KG, Schwerdtle T, Taylor VF, Tokar EJ, Warczak TM, Karagas MR. Opportunities and challenges for dietary arsenic intervention. Environmental Health Perspectives 2018;126(8):84503 (6 pp.). R835442 (2018)
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  • Journal Article Nadeau KC, Li Z, Farzan S, Koestler D, Robbins D, Fei DL, Malipatlolla M, Maecker H, Enelow R, Korrick S, Karagas MR. In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort. Clinical Immunology 2014;155(2):188-197. R835442 (2015)
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  • Journal Article Nygaard UC, Li Z, Palys T, Jackson B, Subbiah M, Malipatlolla M, Sampath V, Maecker H, Karagas MR, Nadeau KC. Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures. PLoS One 2017;12(6):e0179606. R835442 (2017)
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  • Journal Article Paquette AG, Lester BM, Koestler DC, Lesseur C, Armstrong DA, Marsit CJ. Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort. PLoS One 2014;9(8):e104913 (10 pp.). R835442 (2015)
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  • Journal Article Paquette AG, Marsit CJ. The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes. Journal of Cellular Biochemistry 2014;115(12):2065-2072. R835442 (2015)
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  • Journal Article Patel CJ, Kerr J, Thomas DC, Mukherjee B, Ritz B, Chatterjee N, Jankowska M, Madan J, Karagas MR, McAllister KA, Mechanic LE, Fallin MD, Ladd-Acosta C, Blair IA, Teiltelbaum SL, Amos CI. Opportunities and challenges for environmental exposure assessment in population-based studies. Cancer Epidemiology, Biomarkers & Prevention 2017;26(9):1370-1380. R835442 (2018)
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  • Journal Article Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP, Cardis E, Cherrie JW, Christiani DC, Cocco P, Coggon D, Comba P, Demers PA, Dement JM, Douwes J, Eisen EA, Engel LS, Fenske RA, Fleming LE, Fletcher T, Fontham E, Forastiere F, Frentzel-Beyme R, Fritschi L, Gerin M, Goldberg M, Grandjean P, Grimsrud TK, Gustavsson P, Haines A, Hartge P, Hansen J, Hauptmann M, Heederik D, Hemminki K, Hemon D, Hertz-Picciotto I, Hoppin JA, Huff J, Jarvholm B, Kang D, Karagas MR, Kjaerheim K, Kjuus H, Kogevinas M, Kriebel D, Kristensen P, Kromhout H, Laden F, Lebailly P, LeMasters G, Lubin JH, Lynch CF, Lynge E, 't Mannetje F, McMichael AJ, Mclaughlin JR, Marrett L, Martuzzi M, Merchant JA, Merler E, Merletti F, Miller A, Mirer FE, Monson R, Nordby K-C, Olshan AF, Parent M-E, Perera FP, Perry MJ, Pesatori AC, Pirastu R, Porta M, Pukkala E, Rice C, Richardson DB, Ritter L, Ritz B, Ronckers CM, Rushton L, Rusiecki JA, Rusyn I, Samet JM, Sandler DP, de Sanjose S, Schernhammer E, Costantini AS, Seixas N, Shy C, Siemiatycki J, Silverman DT, Simonato L,Smith AH, Smith MT, Spinelli JJ, Spitz MR, Stallones L, Stayner LT, Steenland K, Stenzel M, Stewart BW, Stewart PA, Symanski E, Terracini B, Tolbert PE, Vainio H, Vena J, Vermeulen R, Victora CG, Ward EM, Weinberg CR, Weisenburger D, Wesseling C, Weiderpass E, Zahm SH. IARC Monographs: 40 years of evaluating carcinogenic hazards to humans. Environmental Health Perspectives 2015;123(6):507-514. R835442 (2015)
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  • Journal Article Peng S, Deyssenroth MA, Di Narzo AF, Lambertini L, Marsit CJ, Chen J, Hao K. Expression quantitative trait loci (eQTLs) in human placentas suggest developmental origins of complex diseases. Human Molecular Genetics 2017;26(17):3432-3441. R835442 (2018)
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  • Journal Article Punshon T, Chen S, Finney L, Howard L, Jackson BP, Karagas MR, Ornvold K. High-resolution elemental mapping of human placental chorionic villi using synchrotron X-ray fluorescence spectroscopy. Analytical and Bioanalytical Chemistry 2015;407(22):6839-6850. R835442 (2015)
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  • Journal Article Punshon T, Jackson BP. Essential micronutrient and toxic trace element concentrations in gluten containing and gluten-free foods. Food Chemistry 2018;252:258-264. R835442 (2018)
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  • Journal Article Romano ME, Webster GM, Vuong AM, Zoeller RT, Chen A, Hoofnagle AN, Calafat AM, Karagas MR, Yolton K, Lanphear BP, Braun JM. Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: the HOME Study. Environmental Research 2015;138:453-460. R835442 (2015)
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  • Journal Article Rothenberg SE, Korrick SA, Fayad R. The influence of obesity on blood mercury levels for U.S. non-pregnant adults and children: NHANES 2007-2010. Environmental Research 2015;138:173-180. R835442 (2015)
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  • Journal Article Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, Bohlin J, XuZ, Huang RC, Reese SE, Xu CJ, Baiz N, Hoyo C, Agha G, Roy R, Holloway JW, Ghantous A, Merid SK, Bakulski KM, Kupers LK, Zhang H, Richmond RC, Page CM, Duijts L, Lie RT, Melton PE, Vonk JM, Nohr EA, Williams-DeVane C, Huen K, Rifas-Shiman SL, Ruiz-Arenas C, Gonseth S, Rezwan FI, Herceg Z, Ekstrom S, Croen L, Falahi F, Perron P, Karagas MR, Quraishi BM, Suderman M, Magnus MC, Jaddoe VWV, Taylor JA, Anderson D, Zhao S, Smit HA, Josey MJ, Bradman A, Baccarelli AA, Bustamante M, Haberg SE, Pershagen G, Hertz-Picciotto I, Newschaffer C, Corpeleijn E, Bouchard L, Lawlor DA, Maguire RL, Barcellos LF, Davey Smith G, Eskenazi B, Karmaus W, Marsit CJ, Hivert MF, Snieder H, Fallin MD, Melen E, Munthe-Kaas MC, Arshad H, Wiemels JL, Annesi-Maesano I, Vrijheid M, Oken E, Holland N, Murphy SK, Sorensen TIA, Koppelman GH, Newnham JP, Wilcox AJ, Nystad W, London SJ, Felix JF, Relton CL. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Human Molecular Genetics 2017;26(20):4067-4085. R835442 (2018)
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  • Journal Article Shi X, Miller S, Mwenda K, Onda A, Rees J, Onega T, Gui J, Karagas M, Demidenko E, Moeschler J. Mapping disease at an approximated individual level using aggregate data: a case study of mapping New Hampshire birth defects. International Journal of Environmental Research and Public Health 2013;10(9):4161-4174. R835442 (2016)
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  • Journal Article Shi X, Ayotte JD, Onda A, Miller S, Rees J, Gilbert-Diamond D, Onega T, Gui J, Karagas M, Moeschler J. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA. Environmental Geochemistry and Health 2015;37(2):333-351. R835442 (2016)
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  • Journal Article Signes-Pastor AJ, Vioque J, Navarrete-Munoz EM, Carey M, García de la Hera M, Sunyer J, Casas M, Riano-Galan I, Tardon A, Llop S, Amoros R, Amiano P, Bilbao JR, Karagas MR, Meharg AA. Concentrations of urinary arsenic species in relation to rice and seafood consumption among children living in Spain. Environmental Research 2017;159:69-75. R835442 (2018)
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  • Journal Article Signes-Pastor AJ, Cottingham KL, Carey M, Sayarath V, Palys T, Meharg AA, Folt CL, Karagas MR. Infants' dietary arsenic exposure during transition to solid food. Scientific Reports 2018;8(1):7114 (8 pp.). R835442 (2018)
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  • Journal Article Sverrisson EF, Zens MS, Fei DL, Andrews A, Schned A, Robbins D, Kelsey KT, Li H, DiRenzo J, Karagas MR, Seigne JD. Clinicopathological correlates of Gli1 expression in a population-based cohort of patients with newly diagnosed bladder cancer. Urologic Oncology 2014;32(5):539-545. R835442 (2015)
    R835442 (2016)
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  • Journal Article Carignan CC, Punshon T, Karagas MR, Cottingham KL. Potential exposure to arsenic from infant rice cereal. Annals of Global Health 2016;82(1):221-224. R835442 (2017)
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  • Journal Article Karagas MR, Punshon T, Sayarath V, Jackson BP, Folt CL, Cottingham KL. Association of rice and rice product consumption with arsenic exposure early in life. JAMA Pediatrics 2016;170(6):609-616. R835442 (2017)
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  • Journal Article Houseman EA, Kile M, Christiani D, Tan I, Kelsey KT, Marsit CJ. Reference-free deconvolution of DNA methylation data and mediation by cell composition effects. BMC Bioinformatics 2016;17:259. R835442 (2017)
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  • Journal Article Fried D, Rhyu J, Odata KB, Blunt HB, Karagas MR, Gilbert-Diamond D. Maternal and cord blood vitamin D status and childhood infection and allergic disease: a systematic review. Nutrition Reviews 2016;74(6);387-410. R835442 (2017)
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  • Journal Article Everson TM, Armstrong DA, Jackson BP, Green BB, Karagas MR, Marsit CJ. Maternal cadmium, placental PCDHAC1, and fetal development. Reproductive Toxicology 2016;65:263-271. R835442 (2017)
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  • Journal Article Appleton AA, Jackson BP, Karagas M, Marsit CJ. Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation. Epigenetics 2017;12(8):607-615. R835442 (2017)
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  • Journal Article Cubadda F, Jackson BP, Cottingham KL, Van Horne YO, Kurzius-Spencer M. Human exposure to dietary inorganic arsenic and other arsenic species:State of knowledge, gaps and uncertainties. Science of the Total Environment 2017;579:1228-1239. R835442 (2017)
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  • Journal Article Deyssenroth MA, Peng S, Hao K, Lambertini L, Marsit CJ, Chen J. Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth. BMC Genomics 2017;18(1):520. R835442 (2017)
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  • Journal Article Rokoff LB, Koutrakis P, Garshick E, Karagas MR, Oken E, Gold DR, Fleisch AF. Wood stove pollution in the developed world: a case to raise awareness among pediatricians. Current Problems in Pediatric and Adolescent Health Care 2017;47(6):123-141. R835442 (2017)
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  • Journal Article Nachman KE, Ginsberg GL, Miller MD, Murray CJ, Nigra AE, Pendergrast CB. Mitigating dietary arsenic exposure: current status in the United States and recommendations for an improved path forward. Science of the Total Environment 2017;581-582:221-236. R835442 (2017)
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  • Journal Article Punshon T, Jackson BP, Meharg AA, Warczack T, Scheckel K, Guerinot ML. Understanding arsenic dynamics in agronomic systems to predict and prevent uptake by crop plants. Science of the Total Environment 2017;581-582:209-220. R835442 (2017)
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  • Journal Article Bulka CM, Davis MA, Karagas MR, Ahsan H, Argos M. The Unintended Consequences of a Gluten-Free Diet. Epidemiology 2017;28(3):e24-e25. R835442 (2017)
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  • Supplemental Keywords:

    analytical, biology, child behavior, child growth, children, community-based, decision making, drinking water, environmental chemistry, EPA Region 1, epidemiology, exposure, food processing, geography, ground water, health effects, heavy metals, human health, immunology, infants, measurement methods, metals, neurodevelopment, Northeast, population, public good, public policy, risk, sensitive populations, surveys, susceptibility, vulnerability, water, water safety

    Relevant Websites:

    https://www.dartmouth.edu/~childrenshealth/index.php Exit

    Progress and Final Reports:

    Original Abstract
  • 2014 Progress Report
  • 2016 Progress Report
  • 2017 Progress Report
  • 2018 Progress Report