Data Sheet 1_A Bayesian network meta-analysis of non-pharmacological interventions for neonatal pain management: a clinical effectiveness comparison.xlsx

BackgroundNewborns are particularly vulnerable to pain, and non-pharmacological methods are frequently employed for pain management due to their lack of side effects. However, there is a lack of comprehensive comparison and ranking of the effectiveness of various non-pharmacological interventions.
ObjectiveTo evaluate the effectiveness of non-pharmacological interventions and to determine whether differences exist in the efficacy of various interventions.
DesignSystematic review and network meta-analysis.
Data sourceRCTs studies in MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials from inception to November 1, 2024.
Review methodsUp to November 1, 2024, we conducted a comprehensive search across four databases to identify studies meeting our inclusion criteria. A Bayesian model was employed for the analysis, and heterogeneity was quantified using random-effects standard deviation (RESD), τ², and I² statistics. The certainty of the synthesized evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. This study protocol has been registered with PROSPERO.
ResultsInitially, we identified 20 citations and included 59 trials involving 2,028 participants for network meta-analysis. Due to many interventions being supported by only one or two original studies, we excluded interventions with fewer than three studies. Ultimately, we identified 13 citations, including 31 trials with a total of 1,141 participants. Regarding efficacy, several interventions were found to be effective. Breast milk (BM), sweet taste (ST), Yakson touch (YT), swaddling, and heel warming (HW) demonstrated significant effectiveness, with mean differences (MDs) in NIPS scores as follows: BM vs. control, −1.71 [95% credible interval (CrI): −2.29, −1.17]; ST vs. control, −1.35 (CrI: −2.13, −0.52); YT vs. control, −1.41 (CrI: −2.09, −0.74); swaddling vs. control, −0.65 (CrI: −1.23, −0.13); and HW vs. control, −0.53 (CrI: −0.89, −0.01). In pairwise comparisons between interventions, significant efficacy differences were observed: BM vs. HW, −1.89 (CrI: −2.70, −1.05); BM vs. non-nutritive sucking (NNS), −1.89 (CrI: −2.70, −1.05); BM vs. ST, −0.88 (CrI: −1.61, −0.11); BM vs. YT, −0.82 (CrI: −1.56, −0.03); BM vs. swaddling, −1.59 (CrI: −2.20, −0.78); NNS vs. ST, 0.98 (CrI: 0.11, 1.89); NNS vs. YT, 1.06 (CrI: 0.12, 2.03); and HW vs. YT, 0.89 (CrI: 0.23, 1.69). Notably, NNS was not found to be effective. The Surface Under the Cumulative Ranking Curve (SUCRA) analysis suggested that BM may be the most effective non-pharmacological intervention for neonatal pain management. SUCRA rankings for the interventions were as follows: BM > ST > YT > swaddling > HW > NNS > control. However, the certainty of the evidence ranged from moderate to very low. Heterogeneity assessments indicated a random-effects standard deviation (RESD) of 0.28 (CrI: 0.04, 0.73) in the consistent model and 0.36 (CrI: 0.01, 1.36) in the inconsistent model, with I² = 100% and τ² = 2.22.
ConclusionGiven the limitation of high heterogeneity, this study should be regarded as a clinical effectiveness comparison. Among the included interventions, breast milk (BM), sweet taste (ST), Yakson touch (YT), heel warming (HW), and swaddling were found to be efficacious, while non-nutritive sucking (NNS) was not effective. The top three interventions, based on ranking, were BM, YT, and ST. However, some effects should be interpreted with caution, as they are derived from small sample sizes. Future research should focus on identifying factors associated with individual responses through large, multicenter studies.
Implications for Nursing ManagementFindings will inform nurse managers of an ideal environment for the non-pharmacological pain management for newborn.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023399924, PROSPERO CRD42024567338.

背景
新生儿对疼痛尤为易感，且由于无副作用，非药物疗法常被用于疼痛管理。然而，目前尚缺乏对各类非药物干预措施有效性的全面比较与排序。

目的
评估新生儿疼痛管理中非药物干预措施的有效性，并明确不同干预措施的疗效是否存在差异。

研究设计
系统评价与网络meta分析。

数据来源
检索建库至2024年11月1日的MEDLINE、EMBASE、Web of Science及考克兰对照试验中心注册库（Cochrane Central Register of Controlled Trials）中的随机对照试验（Randomized Controlled Trial, RCT）。

评价方法
截至2024年11月1日，我们对4个数据库开展了全面检索，以筛选符合纳入标准的研究。分析采用贝叶斯模型（Bayesian model），使用随机效应标准差（Random-effects Standard Deviation, RESD）、τ²及I²统计量量化异质性。采用推荐分级、评估、制定与评价（Grading of Recommendations, Assessment, Development and Evaluation, GRADE）方法对合成证据的确定性进行评价。本研究方案已在PROSPERO平台注册。

结果
最初我们检索到20篇引文，纳入59项试验、共计2028名参与者开展网络meta分析。鉴于多数干预措施仅获得1项或2项原始研究支持，我们排除了纳入研究数量少于3项的干预措施。最终纳入13篇引文，包含31项试验、总计1141名参与者。在疗效方面，多项干预措施被证实有效。母乳（Breast milk, BM）、甜味刺激（Sweet taste, ST）、雅克松抚触（Yakson touch, YT）、襁褓包裹及足跟热敷（Heel warming, HW）均表现出显著疗效，其新生儿疼痛评分量表（Neonatal Infant Pain Scale, NIPS）得分的均数差（Mean Differences, MDs）如下：母乳与对照组相比为−1.71 [95%可信区间（95% Credible Interval, CrI）：−2.29, −1.17]；甜味刺激与对照组相比为−1.35（CrI：−2.13, −0.52）；雅克松抚触与对照组相比为−1.41（CrI：−2.09, −0.74）；襁褓包裹与对照组相比为−0.65（CrI：−1.23, −0.13）；足跟热敷与对照组相比为−0.53（CrI：−0.89, −0.01）。在干预措施间的两两比较中，观察到显著的疗效差异：母乳与足跟热敷相比为−1.89（CrI：−2.70, −1.05）；母乳与非营养性吸吮（Non-nutritive sucking, NNS）相比为−1.89（CrI：−2.70, −1.05）；母乳与甜味刺激相比为−0.88（CrI：−1.61, −0.11）；母乳与雅克松抚触相比为−0.82（CrI：−1.56, −0.03）；母乳与襁褓包裹相比为−1.59（CrI：−2.20, −0.78）；非营养性吸吮与甜味刺激相比为0.98（CrI：0.11, 1.89）；非营养性吸吮与雅克松抚触相比为1.06（CrI：0.12, 2.03）；足跟热敷与雅克松抚触相比为0.89（CrI：0.23, 1.69）。值得注意的是，非营养性吸吮未被证实有效。累积排序曲线下面积（Surface Under the Cumulative Ranking Curve, SUCRA）分析显示，母乳可能是新生儿疼痛管理中最有效的非药物干预措施。各干预措施的SUCRA排序如下：BM > ST > YT > 襁褓包裹 > HW > NNS > 对照组。然而，证据的确定性等级从中度到极低不等。异质性评估显示，一致性模型的随机效应标准差为0.28（CrI：0.04, 0.73），非一致性模型为0.36（CrI：0.01, 1.36），I² = 100%，τ² = 2.22。

结论
鉴于存在较高异质性的局限，本研究可视为一项临床有效性对比研究。纳入的干预措施中，母乳（BM）、甜味刺激（ST）、雅克松抚触（YT）、足跟热敷（HW）及襁褓包裹均显示出有效疗效，而非营养性吸吮（NNS）则无明显效果。按疗效排序的前三位干预措施依次为BM、YT及ST。但部分效应值需谨慎解读，因其源自小样本研究。未来研究应通过大型多中心研究，明确与个体应答相关的影响因素。

护理管理启示
本研究结果可为护理管理者提供新生儿非药物疼痛管理的理想环境参考依据。

系统评价注册
https://www.crd.york.ac.uk/PROSPERO/view/CRD42023399924，PROSPERO CRD42024567338。