# Placental Origins of Positive Child Health Outcomes

> **NIH NIH R03** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $64,089

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite numerous early life adversities, some children born extremely preterm (< 28 weeks’ gestation) remain
free of adverse outcomes and have good quality of life. The biological mechanisms underlying protective
pathways leading to positive health outcomes among extremely preterm children are not well-understood.
However, we do know that placental biology plays a key role in determining child health. In this study,
we will
integrate multi-omics placental data, including gene expression, epigenetic regulators of gene expression (DNA
methylation; microRNAs) and genotype to identify critical pathways linked to positive outcomes among children
born extremely preterm. We will investigate an under-studied mechanism—functional changes in gene
expression and placental multi-omics—as an early driver of positive health in children. This is the first study to
explore placental multi-omics related to positive health.
This proposal builds on our preliminary findings from the
multi-center
Extremely Low Gestational Age Newborns (ELGAN; n = 889) study, from which, (1)
we published
findings that
32% of ELGAN children exhibited no adverse health outcomes at age 10, and derived a positive
child health index, strongly associated with quality of life scores; (2) we identified protective prenatal factors (e.g.,
higher maternal education) associated with positive child health that potentially effect biological pathways
influencing health outcomes; and (3) we found that children with positive health at age 10 had reduced
expression of inflammatory genes in the placenta compared with children with adverse outcomes (preliminary
data). The central hypothesis of this proposed study is that reduced placental gene expression of inflammatory
and stress-related pathways is associated with positive child health. We anticipate that these functional changes
in gene expression are tied to microRNAs (miRNAs), DNA methylation and genotype. Our specific aims are to:
1) identify placental gene expression (mRNAs) changes associated with protective prenatal factors and positive
child health outcomes at ages 10 and 15 years; and 2) determine regulators (e.g., DNA methylation) of gene
expression associated with protective prenatal factors and positive child health at ages 10 and 15. This proposal
builds on the existing data of the ELGAN study, which enrolled a cohort of children born < 28 weeks’ gestation,
with follow-up rates of > 80%. From the ELGAN study (funded in the NIH Environmental influences on Child
Health Outcomes (ECHO) program), we have access to: a) placental multi-omics data: gene expression
(mRNAs), epigenetic transcriptional and post-transcriptional regulators of gene expression (miRNAs and DNA
methylation, respectively), and gene sequences (genotype); b) child outcome at ages 10 and 15 years, robust
measures of positive child health outcomes; c) prenatal and age 2 years factors: measures of prenatal factors
and life adversities related to child h...

## Key facts

- **NIH application ID:** 10140400
- **Project number:** 5R03HD101413-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Hudson Santos
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,089
- **Award type:** 5
- **Project period:** 2020-04-08 → 2022-05-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140400

## Citation

> US National Institutes of Health, RePORTER application 10140400, Placental Origins of Positive Child Health Outcomes (5R03HD101413-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10140400. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*