Procedural pain in neonates, particularly during heel lance, remains a significant challenge. The American Academy of Pediatrics (AAP) advocates for pain prevention and management in neonates. However, many heel lances are performed without preprocedural analgesia. Heel lance, while convenient for obtaining capillary blood, is a painful procedure, potentially affecting physiological and behavioral responses and long-term neurodevelopment. Assessing pain in neonates is complex due to their nonverbal nature, requiring multiple assessment tools encompassing physiological (heart rate, respiratory rate, oxygen saturation, blood pressure, cortisol) and behavioral (facial expressions, cries, limb withdrawal) responses. Current clinical practice favors non-pharmacological interventions like breastfeeding and oral sucrose solutions, but challenges exist concerning maternal inability to breastfeed and the long-term effects of repeated sucrose administration. Low-level laser therapy (LLLT), a safe, non-invasive technique, shows promise in pain management in adults and children by blocking nerve fiber conduction and releasing endorphins. However, its application in neonatal heel lance pain management has yielded inconsistent results, with one prior study showing it less effective than oral sucrose when applied to the Yintang acupoint. This study aimed to investigate the analgesic effect of LLLT directly applied to the heel lance site using different parameters, hypothesizing that LLLT would reduce nociceptive pain and associated responses, similar to BM feeding.

Numerous studies have explored non-pharmacological interventions for reducing neonatal procedural pain. Breastfeeding and oral sucrose or glucose solutions are commonly used and demonstrated effectiveness, although challenges like maternal inability to breastfeed and potential long-term effects of sucrose remain. LLLT has shown analgesic, anti-inflammatory, and edema-reducing effects in adults and children. However, its application in neonates for heel lance pain remains understudied, with conflicting results from previous research using different LLLT parameters and application sites. The inconsistent findings highlight the need for further investigation, particularly focusing on optimal LLLT parameters and application locations.

This prospective, single-center, open-label, randomized controlled trial was conducted at Kaohsiung Chang Gung Memorial Hospital from August 2017 to October 2018. 130 healthy term neonates (37-42 weeks gestation, Apgar score ≥7 at 5 min) were targeted; 125 were recruited, and 118 completed the study (55 LLLT, 63 BM). Participants were randomly assigned (1:1 ratio, block randomization with block size 2) to receive either LLLT (1.5 J of energy, 150 mW power, 810 nm wavelength, E 4672 Hz frequency) to the heel lance site for 20 seconds or 5 mL of expressed BM over 2 minutes prior to heel lance. Physiological parameters (heart rate, respiratory rate, oxygen saturation, blood pressure) were monitored before and after heel lance. Behavioral responses (latency to first cry, cry duration, squeeze time) were recorded using digital cameras, alongside pain scores (NPASS and NFCS). Salivary cortisol and α-amylase levels were measured as stress biomarkers at baseline, immediately, and 20 minutes after heel lance. Three blinded investigators assessed videos and physiological data. Data analysis involved chi-square tests (demographic data), independent t-tests (outcome variables), and paired t-tests (salivary biomarkers).

After adjusting for potential confounders, there was no significant difference in latency to the first cry (p = 0.795) or duration of crying (p = 0.062) between the LLLT and BM groups. However, the squeeze time was significantly shorter in the LLLT group (95.07 ± 40.16 s) than in the BM group (122.51 ± 95.98 s, p = 0.047). NPASS and NFCS pain scores showed no significant differences between groups at any time point (baseline, 1, 2, and 3 min after heel lance). No significant differences were observed in physiological parameters (heart rate, respiratory rate, oxygen saturation, blood pressure) before and after heel lance. Regarding salivary biomarkers, there was no significant difference in salivary cortisol and α-amylase levels between the two groups at any time point. However, the BM group showed a significant increase in salivary cortisol 20 minutes post-heel lance (p = 0.006) compared to baseline and immediately after heel lance (p < 0.001), while salivary α-amylase levels were significantly decreased immediately after heel lance (p < 0.001) and then significantly increased 20 minutes after heel lance (p < 0.001) compared to immediately after heel lance in the same group. The LLLT group exhibited no such significant changes in salivary cortisol or α-amylase levels.

The findings suggest that LLLT applied directly to the heel lance site is at least as effective as BM feeding in managing pain during heel lance in healthy term neonates. The shorter squeeze time in the LLLT group is noteworthy, potentially indicating a reduction in procedure-related discomfort. The lack of significant differences in pain scores and physiological parameters between the two groups supports this finding. While the salivary cortisol and α-amylase responses differed between the groups, the absence of significant differences in these biomarkers between the LLLT and BM groups at all time points suggests comparable stress levels. The study's unique aspect is the direct application of LLLT to the heel lance site, which may have improved efficacy compared to previous studies using distant acupoints. The results suggest that LLLT is a promising non-pharmacological analgesic for neonatal procedural pain, potentially offering a valuable alternative or adjunct to BM feeding, particularly when breastfeeding is not feasible.

This study demonstrates the analgesic efficacy of LLLT in managing heel lance pain in healthy term neonates. The results suggest that LLLT provides comparable pain relief to BM feeding with the added benefit of a shorter procedure time. Further research should investigate LLLT's long-term effects on neonatal neurodevelopment and explore its application in diverse clinical settings and populations. LLLT's non-invasive nature and ease of administration highlight its potential as a valuable tool in neonatal pain management.

This study's limitations include its single-center design, potentially limiting the generalizability of findings. A possible confounding factor could be the pressure exerted on the skin by the laser probe, although efforts were taken to minimize this. Ethical considerations arose from using expressed BM as a comparator instead of breastfeeding. Further research with a larger sample size and multiple centers is warranted to validate these findings and address the limitations.