# Clinical and Biochemical Features of Metabolic Dysregulation in Formerly Preterm Children

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $761,618

## Abstract

In the US, ~100,000 babies are born premature at <34 weeks gestational age (GA) each year, or ~2.7% of all
live births. While infant preterm respiratory, pulmonary vascular, and systemic vascular diseases are common
among those born preterm, many become asymptomatic in early childhood. Yet, emerging data point to
subclinical abnormalities among adult survivors of preterm birth that may ultimately drive their increased rates
of long-term cardiopulmonary complications including obstructive lung disease, pulmonary and systemic
hypertension, and metabolic disease including diabetes, obesity and metabolic syndrome. Preterm-born young
adults have systemic evidence of energy metabolism dysregulation, insulin insensitivity and oxidative stress.
This application has four objectives: 1) Understand the cardiopulmonary phenotypic burden of disease among
formerly preterm children (FPC) ages 5-12 years; 2) Evaluate for systemic evidence of metabolic dysregulation
characterized by inflammation, oxidative stress, and insulin resistance in FPC; 3) Explore mechanisms by
determining whether FPC have systemic molecular signatures of abnormal energy metabolism and
inflammation; and, 4) Incorporate metrics of social determinants of health (SDOH), to understand how
exposures interact with and modify the clinical condition as well as systemic and cellular features. There is a
critical need to determine the burden of disease and mechanistic features during mid-childhood, when early
interventions may change an otherwise predetermined lifespan trajectory toward chronic illness. We propose a
strategy of dense clinical phenotyping paired with molecular studies and information about SDOH. We will
leverage the clinical and research infrastructures built at our three centers over the past twenty or more years
in the care and study of children born preterm. We hypothesize that school age FPC display systemic
metabolic energy dysregulation, characterized by inflammation, oxidative stress, and insulin resistance, with
associated cardiopulmonary abnormalities and suboptimal reactivity to stress challenge, and that these
outcomes may be modified by social determinants of health (SDOH). Establishing a new human cohort of 100
FPC ages 5-12 years, matched by 50 formerly term healthy controls, we will pursue the following Aims: Aim 1:
identify the clinical cardiopulmonary vascular features that characterize FPC; Aim 2: identify the biochemical
markers in circulation that suggest metabolic dysregulation characterized by inflammation, oxidative stress,
and insulin resistance; Aim 3: deeply explore mechanistic drivers by generating expression data from RNA
Sequencing to determine the molecular variations that drive alterations in energy metabolism. In each Aim, we
will integrate the phenotypic, biochemical, and molecular variations with socio-ecologic exposures. These
studies will confirm the presence of cardiopulmonary irregularities among FPC in mid-childhood and connect
these phenotypes...

## Key facts

- **NIH application ID:** 10883414
- **Project number:** 1R01HL169859-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Eric Douglas Austin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $761,618
- **Award type:** 1
- **Project period:** 2024-04-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883414

## Citation

> US National Institutes of Health, RePORTER application 10883414, Clinical and Biochemical Features of Metabolic Dysregulation in Formerly Preterm Children (1R01HL169859-01A1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10883414. Licensed CC0.

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