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A Preterm Rat Model for Pain Studies
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Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants.

Tingting Zhao1, Xiaolin Chang2, Subrata Kumar Biswas3

  • 1School of Nursing, Yale University, Orange, Connecticut, USA, t.zhao@yale.edu.

Developmental Neuroscience
|January 29, 2024
PubMed
Summary

Early life pain and stress in preterm infants are linked to neurodevelopmental outcomes. Specific mitochondrial proteins identified in buccal cells may help predict these outcomes.

Keywords:
Mass spectrometryMitochondrial dysfunctionPain/stressPreterm infants

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Area of Science:

  • Neonatal research
  • Neuroscience
  • Mitochondrial biology

Background:

  • Preterm infants face significant pain and stress during neonatal intensive care unit (NICU) hospitalization, impacting neurodevelopmental outcomes.
  • Mitochondrial function is a potential link between perinatal stress and neurodevelopment, but specific proteins involved remain unidentified.

Purpose of the Study:

  • To investigate the associations between early life pain/stress, mitochondrial function-related proteins, and neurobehavioral responses in preterm infants.
  • To identify potential protein biomarkers in buccal cells for predicting neurodevelopmental outcomes.

Main Methods:

  • Prospective cohort study of 33 preterm infants.
  • Daily pain/stress documentation and NICU Network Neurobehavioral Scale (NNNS) assessments at 36-38 weeks post-menstrual age.
  • Mass spectrometry-based proteomics on buccal epithelial cells, with Lasso and multiple linear regression analyses.

Main Results:

  • Preterm premature rupture of membranes (PPROM) was negatively associated with neurobehavioral outcomes.
  • Certain protein functions (e.g., oxidative stress response, lipid metabolism) were negatively associated with neurodevelopment, while others (e.g., cytoskeletal regulation) were positively associated.
  • Specific mitochondrial proteins (e.g., SPRR2A, PAIP1, MT-CO2) showed positive associations with favorable neurodevelopment, while others (e.g., ABLIM1, keratins) were linked to adverse outcomes.

Conclusions:

  • Mitochondrial function-related proteins are associated with early life pain/stress and infant neurodevelopmental outcomes.
  • Buccal protein analysis shows promise for predicting neurobehavioral outcomes in preterm infants.
  • Further large-scale longitudinal studies are recommended.