There is strong evidence that the environment experienced in utero contributes to cardiovascular, metabolic, immunologic, and nervous system health during both childhood and adulthood. Defining children at-risk early in life is critical to improving health outcomes;biomarkers of exposure and outcome are powerful tools to use in risk identification and offer an opportunity to inform the mechanisms involved in the developmental origins of disease. Emerging evidence, from our own laboratories and others, suggests that the placenta, as a master regulator of the intrauterine environment and of fetal development, plays a critical role in the developmental origins of health and disease. Thus, the placenta is an ideal tissue in which to identify functional biomarkers that mediate fetal programming of health. In published and preliminary studies we have demonstrated that exposures, such as arsenic, can alter the patterns of DNA methylation and of gene expression in primary human placental tissue, and we have demonstrated that such alterations are associated with fetal growth and newborn neurobehavioral measures.
We aim here to develop novel biomarkers of exposure and outcome by examining the hypothesis that environmental exposures encountered by a pregnant woman impact the epigenetic and gene expression profiles of the infant's placenta and these functional alterations are associated with poor-health outcomes in the children. We will employ the existing resources of the ongoing New Hampshire Birth Cohort Study, and its established biorepository of placental tissues, to allow sensitive and robust assessment of gene expression and genomewide DNA methylation in combination with infant and maternal biomarkers of arsenic exposure. We propose to use state-of-the-art genomic technologies to identify and validate novel profiles of DNA methylation and gene expression susceptible to environmental exposure in human placenta and to examine their association with newborn outcomes including growth, infection and neurodevelopment being assessed in Projects 1 and 2 of the Program. These examinations will provide critical insight into the mechanisms of the developmental origins of lifelong health, highlight novel pathways affected by exposures that drive children's health, and identify novel biomarkers which can be used to find at the earliest points of life, children at-risk so necessary interventions can be employed soon enough to prevent future disease.

Public Health Relevance

The placenta serves as a key functional organ in defining the environment encountered by a developing fetus. Understanding and defining molecular alterations to the placenta associated with exposure and with adverse outcomes will allow for early identification of at-risk children and will provide insight onto novel pathways to target for targeted preventative approaches.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dartmouth College
United States
Zip Code
Romano, Megan E; Eliot, Melissa N; Zoeller, R Thomas et al. (2018) Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study. Int J Hyg Environ Health 221:623-631
Everson, Todd M; Punshon, Tracy; Jackson, Brian P et al. (2018) Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts. Environ Health Perspect 126:017010
Emond, Jennifer A; Karagas, Margaret R; Baker, Emily R et al. (2018) 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. J Nutr 148:22-30
Caito, Samuel W; Jackson, Brian P; Punshon, Tracy et al. (2018) Editor's Highlight: Variation in Methylmercury Metabolism and Elimination Status in Humans Following Fish Consumption. Toxicol Sci 161:443-453
Braun, Joseph M; Chen, Aimin; Hoofnagle, Andrew et al. (2018) Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels. Horm Behav 101:77-84
Punshon, Tracy; Jackson, Brian P (2018) Essential micronutrient and toxic trace element concentrations in gluten containing and gluten-free foods. Food Chem 252:258-264
White, Alexandra J; O'Brien, Katie M; Jackson, Brian P et al. (2018) Urine and toenail cadmium levels in pregnant women: A reliability study. Environ Int 118:86-91
Felix, Janine F; Joubert, Bonnie R; Baccarelli, Andrea A et al. (2018) Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol 47:22-23u
Everson, Todd M; Marsit, Carmen J (2018) Integrating -Omics Approaches into Human Population-Based Studies of Prenatal and Early-Life Exposures. Curr Environ Health Rep 5:328-337
Chernikova, Diana A; Madan, Juliette C; Housman, Molly L et al. (2018) The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth. Pediatr Res 84:71-79

Showing the most recent 10 out of 123 publications