# Placental Epigenome and Brain Dysfunction after Preterm Birth

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $620,297

## Abstract

Project Summary/Abstract
This project addresses a critical gap in the understanding of sexual dimorphism in both infant and children’s
health outcomes, where males are often at increased risk for disease. At the project’s core is the novel
hypothesis that sexual epigenetic dimorphism in the placenta influence responses to perinatal stressors, and
predict fetal growth restriction and neurodevelopment ND later in life. To address this, we use an “-omics” and
systems-wide approach to identify biomarkers of, and potential mechanisms for, adverse pregnancy outcomes
(fetal growth restriction and neurodevelopmental impairment in the offspring) in an existing cohort of children
born extremely prematurely (i.e., before 28 weeks of gestation). The –omics approaches include DNA CpG
methylomics, transcriptomics to assess messenger RNA), and proteomics. A tremendous strength of this
proposal is the unique and extensively characterized US-based cohort recruited for the Extremely Low
Gestation Age Newborn (ELGAN) Study. Since its initiation in 2001, the broad goal of the ELGAN Study has
been to evaluate the relationship between perinatal inflammation and neurodevelopmental impairments among
individuals born extremely premature. In the proposed project, we build on the success of the ELGAN Study
by: 1) evaluating “-omics” biomarkers in archived specimens of placenta and neonatal blood and 2) integrating
these data with existing outcome data about fetal growth restriction and neurodevelopmental impairments in
the ELGAN cohort. In the first three years of the project, DNA CpG methylation, mRNA, and selected proteins
will be assayed in archived specimens of placenta and neonatal blood. Data analyses will begin in year 2, with
an initial focus on establishing the relationships among placental and blood biomarkers and both fetal growth
restriction as well as neurodevelopmental impairment. We also will study relationships between prenatal
factors associated with adverse pregnancy outcomes (maternal obesity and placental bacteria) and placental
and neonatal blood –omics biomarkers. Furthermore, we will evaluate relationships between will placenta
biomarkers and neonatal blood biomarkers. Innovative aspects of this project include its longitudinal
perspective, consideration of placenta epigenetics as a mechanism linking prenatal exposures to childhood
outcomes, and evaluation of CpG methylation marks in neonatal blood. With the potential for public health
impact, this research may inform the development of therapies targeting epigenetic processes to prevent or
ameliorate cognitive disability, thereby improving the quality of life for 16,000 individuals who survive extremely
premature birth each year in the United States.

## Key facts

- **NIH application ID:** 9933965
- **Project number:** 5R01HD092374-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Rebecca Fry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,297
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933965

## Citation

> US National Institutes of Health, RePORTER application 9933965, Placental Epigenome and Brain Dysfunction after Preterm Birth (5R01HD092374-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9933965. Licensed CC0.

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