Objective Assessment of Procedural Pain and Recovery in Preterm Infants Using Time–Frequency Analysis of Electroencephalography

Background: Pain management for preterm infants has emerged as a key intervention aimed at enhancing their developmental trajectories. However, little is known regarding the response and recovery of the neonatal brain following procedural pain. This study examined the temporal dynamics of electroencephalography (EEG) power in preterm infants during and up to 30 min after procedural pain. Methods: fifty-seven datasets were collected from preterm infants (mean gestational age 32.5 ± 3.3 weeks). We computed Time–Frequency analysis for EEG power and EEG power ratio relative to baseline across eight EEG channels in the low delta (1–2 Hz), high delta (2–4 Hz), theta (4–8 Hz), alpha (8–16 Hz), and beta (16–20 Hz) during the procedure, immediately after, and at intervals up to 30 min post-procedure. Results: EEG power increased significantly in all channels and frequency bands during the procedure compared to baseline (p < 0.05), declined immediately after but remained above baseline (p < 0.05), and recovered to near-baseline levels by four minutes post-procedure (p > 0.05), except for alpha and beta power at C3 and C4, which were lower than baseline (p < 0.05). The EEG power ratio at the frontal, occipital, and temporal showed the greatest power changes in the beta. The C3 and C4 exhibited the most prominent relative changes in the low delta. Conclusion: the preterm brain exhibits widespread responses to procedural pain and recovers gradually, not returning to the resting state for at least four minutes after a painful procedure. These results underscore the potential benefit of quantifying the time-integral of EEG power, rather than its peak intensity, when developing a biosensor for procedural pain using neonatal EEG.