Laser acupuncture versus oral glucose administration for pain prevention in term neonates: an observer-blinded non-inferiority randomized controlled clinical trial

Background: Neonates undergoing intensive care are routinely submitted to minor painful procedures such as heel lances. Pharmacological treatment is limited in neonatal care and not recommended for minor painful interventions. Hence, non-pharmacological acute pain management is an important subject. Acupuncture could be a new strategy for neonatal pain prevention. Accordingly, the aim of the present study was to investigate whether laser acupuncture is non-inferior to oral sweet solutions in pain prevention. Methods: In total, 96 healthy term neonates were randomly assigned to receive either laser acupuncture with 10 mW at LI4 bilaterally (AG, acupuncture group) or 30% oral glucose solution (GG, glucose group) before heel lance for metabolic screening. The primary outcome was the difference in premature infant pain profile (PIPP) score between groups in a non-inferiority concept. Secondary outcomes were changes in heart rate and crying time. Results: Median (interquartile range) PIPP scores were comparable in the AG and GG (12 (10-14) vs 12 (9-14), p = 0.981). Nevertheless, the 95% confidence interval (CI) of location shift exceeded the predefined margin for non-inferiority of 1 (95% CI: -1.000006 to 1.000059). Heart rate was found to be significantly lower after intervention (p = 0.048) and after heel lance (p = 0.015) in the AG versus GG. There was no difference in crying time between groups (p = 0.890). Conclusion: Laser acupuncture was not shown to be non-inferior to an oral glucose solution, possibly due to the higher than expected variability in PIPP scores within the studied groups. Future neonatal laser acupuncture studies for pain prevention with higher sample sizes are therefore warranted.