# Impaired Brain Development in a Premature Ex-utero Environment

> **NIH NIH R01** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $734,286

## Abstract

ABSTRACT
Despite significant advances in survival and the decreased risk of major brain injury in premature infants, the
persistent high prevalence of long-term remains a major public health problem, with enormous personal,
familial, and societal costs. There is growing evidence that impaired structural brain development is detectable
in premature infants before term corrected age, even without overt destructive brain injury. Together these
observations suggest that brain dysmaturation in an artificial ex-utero environment disturbs neuropsychological
development in prematurity survivors. In turn, this points to ongoing gaps between the effectiveness of current
support/protection strategies for ex-utero preterm brain development, and that provided by the normal in-utero
environment. Critical to closing this gap is identifying the disruptive interactions between the complex shifting
landscape of brain maturation/vulnerability, and preterm ex-utero exposures, among which circulatory and
oxygenation (C/O) exposures are considered a leading cause of neuropsychologic impairment. To approach
this challenge the necessary steps are: to identify the earliest deviations of ex-utero brain maturation compared
to normal in-utero brain maturation; to identify the temporal relationship between the onset of brain
dysmaturation and preceding C/O exposures; and, to confirm that the early preterm maturational changes
predict structural brain development at term-corrected age, and later functional outcome. To date, progress
has been impeded by (i) the lack of reference data for normal in-utero brain development, (ii) the lack of serial
measurements of ex-utero preterm brain development, and (iii) the lack concurrent biomarkers that capture
continuous C/O exposures. Using our large repository of normal in-utero brain development and multimodal
quantitative MRI, our preliminary studies show significant anatomic differences in brain development occurring
in utero vs. ex utero, detectable well before term-equivalent age. We have developed systems for measuring
and analyzing continuous physiological signals in sick preterm infants. In this proposal we combine serial 4-
weekly MRI with concurrent exposure measurements in infants born <36 weeks gestation, to establish the
relationship between disturbed early brain maturation, specific preterm C/O exposures, and their association
with long-term neuropsychological impairment. These findings may inform future brain-oriented support of
premature infants, identify specific targets for neuroprotection, and lead to improved neuropsychological
outcomes.

## Key facts

- **NIH application ID:** 9973941
- **Project number:** 1R01HD099393-01A1
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** ADRE Jacques DU PLESSIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $734,286
- **Award type:** 1
- **Project period:** 2020-03-12 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973941

## Citation

> US National Institutes of Health, RePORTER application 9973941, Impaired Brain Development in a Premature Ex-utero Environment (1R01HD099393-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973941. Licensed CC0.

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