# Maternal Hypoxemia and Oxidative Stress in the Fetus, Newborn, and Adult

> **NIH NIH R03** · LOMA LINDA UNIVERSITY · 2020 · $79,000

## Abstract

Project Summary Persistent pulmonary hypertension of the newborn is poorly understood although
gestational long term hypoxia is a significant risk factor in its development as infants born at high altitude have
as much as 100-fold increased risk of developing disease. Recent studies illustrate that high altitude newborn
lambs have elevated baseline pulmonary artery pressures and greater increases in pulmonary artery pressure
in response to acute hypoxia. Even though the underlying mechanisms remain largely unknown, high altitude
fetal and newborn sheep have cardio-pulmonary problems that are similar to human infants and consistent with
the development of pulmonary hypertension including right heart cardiomyopathy and reduced pulmonary
vasodilation. High altitude exposure can enhance anaerobic glycolysis, depress aerobic metabolism as well as
induce oxidative stress and promote inflammation. These fundamental changes in cellular metabolism, and
underlying changes in protein expression may provide unique metabolic signatures and contribute in novel
ways to the development of pulmonary hypertension in the newborn. In Specific Aim 1 the proposed study will
test the hypothesis that LTH results in discernable differences in primary metabolism, oxidative stress and
inflammation that will be detected in the metabolic profile and proteins found in the plasma of the fetus and
newborn. Specific Aim 2 will then test the hypothesis that LTH modifies pulmonary vascular development
impacting primary metabolism and augmenting oxidative stress and inflammation. Plasma and pulmonary
arterial samples isolated from near term fetal, two-week -old newborn lambs, and adult sheep maintained
near sea level (300 m) or at high altitude (3,801 m) will be used to test these hypotheses. Proteomic analysis
and metabolomics profiling will then be performed, including untargeted metabolic profiling of energy
metabolism and targeted analysis for endocannabinoids and oxylipins, which markers of oxidative stress and
inflammation. The findings of these studies will provide groundwork to advance our knowledge of the biomarkers
associated with gestational hypoxia-induced pulmonary hypertension in the newborn and improve our
understanding of pathophysiological mechanisms underlying the development of disease. These studies will
provide new insights and a proof of concept regarding the development of new diagnostic biomarkers for
detection of pulmonary hypertension in the newborn. The studies will also bring to light potential therapeutic
strategies that may be beneficial for the treatment of infants with pulmonary hypertension. This is of critical
importance given the extreme limit of effective therapeutic intervention currently available for this important
clinical problem in newborns.

## Key facts

- **NIH application ID:** 9882516
- **Project number:** 5R03HD098477-02
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **Principal Investigator:** SEAN M WILSON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,000
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882516

## Citation

> US National Institutes of Health, RePORTER application 9882516, Maternal Hypoxemia and Oxidative Stress in the Fetus, Newborn, and Adult (5R03HD098477-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9882516. Licensed CC0.

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