# "Preterm lung and brain responses to mechanical ventilation and corticosteroids"

> **NIH NIH R21** · SAINT LOUIS UNIVERSITY · 2020 · $281,638

## Abstract

Almost all very low birth weight preterm infants require respiratory support (mechanical ventilation or CPAP) at
birth, and up to 40% of these infants will develop bronchopulmonary dysplasia (BPD). Since BPD affects the
smallest and most preterm infants, many of the infants surviving with BPD have neurodevelopmental disabilities
and injuries to other organs. Lung inflammation and injury resulting from mechanical ventilation are central to
the development of BPD. Prolonged mechanical ventilation has been linked to MRI changes and poor neurologic
outcomes, and mechanical ventilation causes systemic changes in liver, brain inflammation and MRI changes in
sheep. Recent trials of inhaled budesonide, budesonide mixed with surfactant, postnatal dexamethasone, and
early postnatal low-dose hydrocortisone have all decreased the risk of BPD. However, concerns exist for
systemic effects of steroids. Different postnatal steroids regimens have been associated with worse neurologic
outcomes. The balance between a lung benefit and neurologic harm for these regimens needs to be determined
before widespread use. Our preliminary data demonstrate systemic changes in the liver and brain with
mechanical ventilation that can be altered by postnatal steroids. Using a preterm lamb models, we will evaluate
lung and brain responses to mechanical ventilation and postnatal steroids, and identify possible toxic effects on
the newborn. By combining antenatal exposures to corticosteroid and mechanical ventilation, we can determine
interactions that could alter lung maturation and postnatal lung function. Results will be assessed using
physiology, pathology, and advanced molecular techniques for the lung and brain. We will use mRNA
sequencing to evaluate a wide range of potential injury pathways. We propose two specific aims to 1) define the
role of clinically relevant steroids (dexamethasone, budesonide in surfactant, hydrocortisone) in mechanical
ventilation and 2) interactions with antenatal corticosteroids and mechanical ventilation on brain injury. Our
proposal is innovative because it uses unique preterm sheep models to evaluate the lung and brain effects of
postnatal steroids in clinically relevant settings of lung injury and antenatal steroids. These exploratory studies
fit well with the R21 mechanism and will provide important information for assisting clinical decisions in the NICU.

## Key facts

- **NIH application ID:** 9873727
- **Project number:** 1R21HD100721-01
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** NOAH H HILLMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $281,638
- **Award type:** 1
- **Project period:** 2020-07-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873727

## Citation

> US National Institutes of Health, RePORTER application 9873727, "Preterm lung and brain responses to mechanical ventilation and corticosteroids" (1R21HD100721-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9873727. Licensed CC0.

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