# Pain, Opioids, and Functional Connectivity in Preterm Infants

## TL;DR

This study explores how pain and opioids affect brain activity in preterm infants and how these effects might predict future cognitive development.

## Contribution

The study introduces multivariate EEG-based indexes to assess the impact of pain and opioids on preterm brain function and neurodevelopmental outcomes.

## Key findings

- Higher pain exposure is linked to increased Brain Symmetry Index (BSI) and decreased COC μ and δ wave COC values.
- Opioids like fentanyl and morphine influence specific EEG features differently across frequency bands.
- COC values related to δ waves are positively associated with cognitive outcomes at 24 months.

## Abstract

Aim: To investigate the impact of pain on some electroencephalographic (EEG) features at term equivalent age (TEA) and, second, to assess if the proposed EEG analysis may be predictive of the neurodevelopmental outcome at 24 months corrected age. Methodology: Infants born < 32 weeks of gestational age, without major brain injury, were studied with an 8-channel EEG recording at TEA. The number of skin-breaking procedures from birth to the EEG recording was collected, as well as opioid administration. The following EEG-based indexes were investigated: Brain Simmetry Index (BSI) and Circular Omega Complexity (COC). Multivariate statistical analysis was performed. Results: Seventy-seven preterm newborns were enrolled. The multivariate models showed that higher pain exposure resulted in higher BSI, lower COC μ (mean), and lower COC values related to δ waves (all p < 0.05). Fentanyl was associated with increased BSI values related to α and β waves (all p < 0.05). Morphine showed a positive effect on BSI and a negative effect on OC μ and COC on all frequency bands (all p < 0.05). COC related to δ waves was positively associated with cognitive outcomes (p = 0.034). Conclusions: Pain and opioids might impact brain dynamics in preterm infants. Quantitative multivariate EEG indexes may be helpful to characterize the neurodevelopmental outcomes.