Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants

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.