To synthesize evidence on physiological correlates of pain in preterm infants to identify consistent objective indicators of pain from studies published between January 2017 and December 2025.
Key Findings:
Painful procedures induced significant increases in heart rate (mean difference +12.6 bpm, p < 0.001) and cortisol levels (SMD = +0.68, p < 0.01).
Decreases were observed in heart rate variability (SMD = -0.81, p < 0.001), oxygen saturation (-4.3%, p < 0.01), melatonin (SMD = -0.54, p < 0.05), and cerebral oxygenation (-8.5%, p < 0.001).
The strongest effects were noted in cardiorespiratory parameters (SMD = 0.91).
Interpretation:
Limitations:
Variability in study design, gestational age ranges, pain assessment tools, and NICU practices limited generalizability.
No significant publication bias was detected.
Conclusion:
Integrating objective physiological indicators into neonatal pain assessment may enhance early recognition and improve pain management practices.
