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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
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Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an

James P Boardman1,2, Ruth Andrew3, Mark E Bastin2

  • 1Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK James.Boardman@ed.ac.uk.

BMJ Open
|September 16, 2024
PubMed

Insights

This study investigates how preterm birth impacts infant brain development, focusing on stress and immune factors. Understanding these links is crucial for improving neurodevelopmental outcomes in premature infants.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pediatrics

Background:

  • Preterm birth (PTB) is linked to encephalopathy of prematurity (EoP) and neurocognitive impairment.
  • The biological pathways connecting PTB to atypical brain development remain unclear.
  • Investigating neuroendocrine stress and immune dysregulation may elucidate these links.

Purpose of the Study:

  • To determine the roles of neuroendocrine stress activation and immune dysregulation in linking PTB to EoP.
  • To elucidate the biological mechanisms underlying brain development alterations in preterm infants.
  • To identify risk factors associated with PTB that impact neurodevelopmental outcomes.

Main Methods:

  • The PRENCOG cohort study recruits mother-infant dyads (200 preterm, 100 term births).
  • Data collection includes medical, demographic, socioeconomic, and extensive biological samples (placenta, cord blood, hair, saliva, blood spots, feces).
  • Brain imaging (MRI) will characterize EoP using morphometric similarity networks, hierarchical complexity, and magnetisation transfer saturation imaging, analyzed with regression and structural equation modeling.

Main Results:

  • Analysis will assess the relationship between PTB risk factors and brain imaging metrics of EoP.
  • Structural equation modeling will investigate the mediating roles of stress and immune pathways.
  • Linking neonatal and pupil databases will inform PTB risk factor selection based on educational outcomes.

Conclusions:

  • This research aims to clarify the mechanisms linking preterm birth to adverse brain development.
  • Findings will advance understanding of encephalopathy of prematurity and neurocognitive impairment.
  • The study will provide causal evidence for interventions to improve neurodevelopmental outcomes in preterm infants.
Abstract

Keywords:
Developmental neurology & neurodisabilityImmunityMachine LearningMagnetic Resonance ImagingNeonatal intensive & critical carePhysiological Stress

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