Urlesberger Berndt, Cabano Rita, Soll Greg, Pahl Adrienne, Oei Ju Lee, Schmölzer Georg M, Raith Wolfgang, Bruschettini Matteo
Division of Neonatology, Medical University Graz, Graz, Austria.
Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Cochrane Database Syst Rev. 2025 Feb 21;2(2):CD014160. doi: 10.1002/14651858.CD014160.pub2.
Neonatal abstinence syndrome (NAS) is a drug-withdrawal syndrome, mostly occurring after antenatal exposure to opioids. A neonate may be born physically dependent on opioid medications, which causes withdrawal symptoms (such as high-pitched crying, disruptions in the sleep-wake cycle and tremors) after birth. This is diagnosed with a standardised withdrawal assessment, such as the Finnegan score. Newborns developing NAS require medical treatment and longer hospital stays after birth than neonates without this condition. Treatments for NAS include multiple multimodal treatments to ease symptoms of withdrawal, such as swaddling, 'rooming in' and breastfeeding. If the standardised assessment exceeds a certain threshold, newborns are treated pharmacologically with an orally administered opioid. However, optimal NAS management continues to be debated. Acupuncture has been proposed as a potential intervention. Acupuncture involves stimulation of specific points on the body, either through the insertion of thin metal needles or with techniques that do not penetrate the skin, such as acupressure and laser.
To assess if acupuncture (acupressure, needle, laser) reduces the treatment duration of neonatal abstinence syndrome (NAS) in newborn infants, reduces adverse events and reduces length of hospital stay.
We used bibliographic databases (CENTRAL, PubMed, Embase) and trial registries, together with reference checking, citation searching and contact with study authors, to identify the studies that are included in the review. The latest search date was 25 August 2023.
We included randomised controlled trials (RCTs) or quasi-RCTs, and cluster-randomised trials. We included infants born at full term and late preterm who were diagnosed with NAS within the first 72 hours after birth (i.e. showing significant signs as assessed using a standardised NAS assessment tool, e.g. presenting with withdrawal syndrome and Finnegan score > 8). We included studies where acupuncture (using invasive or non-invasive techniques) was compared with: 1) no intervention; 2) placebo or sham treatment; 3) any pharmacological treatment; or 4) another type of acupuncture (e.g. penetration of the skin with a needle versus acupressure). Acupuncture could be given alone or in combination with conventional medical treatment for NAS ('standard care'), as long as the latter was administered to the control group as well.
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were duration of any pharmacological treatment for NAS, adverse events and length of hospital stay. We used GRADE to assess the certainty of evidence.
We included two single-centre RCTs (104 infants). Both studies compared non-invasive acupuncture added to standard care versus standard care. There were no studies where acupuncture was compared with placebo or sham treatment, pharmacological treatment or with another type of acupuncture. We did not identify any ongoing studies. One of the included studies was conducted with 28 babies in Austria, between 2009 and 2014; it was a prospective, blinded RCT of laser acupuncture, which was performed daily at ear and body acupuncture points, bilaterally, until morphine was discontinued. The other study was conducted with 76 babies in the USA between 1992 and 1996. It was a randomised, prospective, but unblinded study of acupressure: a small herbal seed was taped to an ear acupoint or acupoints, and the seed site was massaged for 30 to 60 seconds after each NAS scoring event. The evidence is very uncertain about the effect of adding acupuncture to standard care on the following outcomes. • Duration of any pharmacological treatment for NAS. In one study, the median duration was 28 days (interquartile range (IQR) 22 to 33) and 39 days (IQR 32 to 48) in the acupuncture and control groups, respectively; in the other study, the mean duration of any pharmacological treatment for NAS was 22.1 days (standard deviation (SD) 16.6) and 22.7 days (SD 13.8) in the acupuncture and control groups, respectively (mean difference (MD) -0.60, 95% CI -7.45 to 6.25; 1 study, 76 infants). • Adverse events. Both studies reported that no adverse effects occurred (risk difference (RD) 0.00 95% CI -0.05 to 0.05; 2 studies, 104 infants; I = 0). • Length of hospital stay in days. In one study (28 infants), the median and IQR were 35 (25 to 47) days and 50 (36 to 66) days in the acupuncture and control groups, respectively. In the other study (76 infants), the mean duration of any pharmacological treatment for NAS was 25.8 days (SD 16.4) and 26 days (SD 13.3) in the acupuncture and control groups, respectively (MD -0.20, 95% CI -6.90 to 6.50; 1 study, 76 infants). • Highest score in a single standardised NAS assessment. One study (28 infants) reported median scores of 15 (IQR 13 to 18) and 16 (IQR 14 to 19) in the acupuncture and control groups, respectively; the other study (76 infants) reported that the average NAS score per scoring event was slightly lower (mean 4.95, SD 1.00) for the 'control' infants than for the infants assigned to acupuncture (mean 5.27, SD 1.04). We judged the certainty of the evidence to be very low for all these outcomes. No studies reported data on all-cause mortality, pain or long-term follow-up.
AUTHORS' CONCLUSIONS: The limited available evidence is insufficient to establish the benefits and harms of acupuncture for the management of NAS in newborn infants. Both studies we included in this review assessed non-invasive acupuncture and reported no adverse effects; however, data are drawn from a very small sample. In light of current limitations, clinicians are urged to approach the use of acupuncture in newborn infants with NAS cautiously, as there is currently no evidence to support its routine application. This systematic review highlights the need for well-conducted, large randomised controlled trials to achieve an optimal information size to assess both the benefits and harms of acupuncture for NAS. In addition, comparisons of acupuncture techniques and sites should be made to assess effectiveness and feasibility.
新生儿戒断综合征(NAS)是一种药物戒断综合征,大多发生在产前接触阿片类药物之后。新生儿可能在出生时就对阿片类药物产生身体依赖,这会导致出生后出现戒断症状(如高声哭闹、睡眠 - 觉醒周期紊乱和震颤)。这是通过标准化的戒断评估(如芬尼根评分)来诊断的。与未患此病的新生儿相比,患NAS的新生儿出生后需要接受医学治疗且住院时间更长。NAS的治疗包括多种多模式治疗以缓解戒断症状,如襁褓包裹、母婴同室和母乳喂养。如果标准化评估超过一定阈值,新生儿会接受口服阿片类药物的药物治疗。然而,NAS的最佳管理仍存在争议。有人提出针灸可能是一种干预方法。针灸包括通过插入细金属针或采用不穿透皮肤的技术(如指压和激光)刺激身体上的特定穴位。
评估针灸(指压、针刺、激光)是否能缩短新生儿戒断综合征(NAS)患儿的治疗时长,减少不良事件并缩短住院时间。
我们使用了文献数据库(CENTRAL、PubMed、Embase)和试验注册库,同时进行参考文献核对、引文检索并与研究作者联系,以确定纳入本综述的研究。最新检索日期为2023年8月25日。
我们纳入随机对照试验(RCT)或半随机对照试验以及整群随机试验。我们纳入足月和晚期早产儿,这些婴儿在出生后72小时内被诊断为NAS(即使用标准化NAS评估工具评估显示出明显体征,如出现戒断综合征且芬尼根评分>8)。我们纳入将针灸(使用侵入性或非侵入性技术)与以下情况进行比较的研究:1)不干预;2)安慰剂或假治疗;3)任何药物治疗;或4)另一种类型的针灸(例如针刺穿透皮肤与指压)。针灸可以单独使用或与NAS的常规医学治疗(“标准护理”)联合使用,只要后者也给予对照组即可。
我们采用Cochrane期望的标准方法程序。我们的主要结局是NAS的任何药物治疗时长、不良事件和住院时间。我们使用GRADE来评估证据的确定性。
我们纳入了两项单中心RCT(共104名婴儿)。两项研究均比较了在标准护理基础上加用非侵入性针灸与标准护理。没有研究将针灸与安慰剂或假治疗、药物治疗或另一种类型的针灸进行比较。我们未识别到任何正在进行的研究。其中一项纳入研究于2009年至2014年在奥地利对28名婴儿进行;这是一项关于激光针灸的前瞻性、双盲RCT,每天在耳部和身体穴位双侧进行激光针灸,直至停用吗啡。另一项研究于1992年至1996年在美国对76名婴儿进行。这是一项关于指压的随机、前瞻性但非双盲的研究:将一颗小 herbal 种子贴在一个或多个耳部穴位上,每次NAS评分后对种子贴敷部位按摩30至60秒。关于在标准护理基础上加用针灸对以下结局的影响,证据非常不确定。
• NAS的任何药物治疗时长。在一项研究中,针灸组和对照组的中位时长分别为28天(四分位间距(IQR)22至33)和39天(IQR 32至48);在另一项研究中,针灸组和对照组NAS的任何药物治疗的平均时长分别为22.1天(标准差(SD)16.6)和22.7天(SD 13.8)(平均差(MD) -0.60,95%CI -7.45至6.25;1项研究,76名婴儿)。
• 不良事件。两项研究均报告未发生不良反应(风险差(RD)0.00,95%CI -0.05至0.05;2项研究,104名婴儿;I² = 0)。
• 以天为单位的住院时间。在一项研究(28名婴儿)中,针灸组和对照组的中位值和IQR分别为35(25至47)天和50(36至66)天。在另一项研究(76名婴儿)中,针灸组和对照组NAS的任何药物治疗的平均时长分别为25.8天(SD 16.4)和26天(SD 13.3)(MD -0.20,95%CI -6.90至6.50;1项研究,76名婴儿)。
• 单次标准化NAS评估中的最高分。一项研究(28名婴儿)报告针灸组和对照组的中位分数分别为15(IQR 13至18)和16(IQR 14至19);另一项研究(76名婴儿)报告,“对照”婴儿每次评分事件的平均NAS分数略低于分配到针灸组的婴儿(分别为平均4.95,SD 1.00和平均5.27,SD 1.04)。我们判断所有这些结局的证据确定性都非常低。没有研究报告全因死亡率、疼痛或长期随访的数据。
现有的有限证据不足以确定针灸治疗新生儿NAS的益处和危害。我们纳入本综述的两项研究均评估了非侵入性针灸且未报告不良反应;然而,数据来自非常小的样本。鉴于目前的局限性,敦促临床医生谨慎对待在患NAS的新生儿中使用针灸,因为目前没有证据支持其常规应用。本系统综述强调需要进行良好设计的大型随机对照试验,以获得足够的样本量来评估针灸治疗NAS的益处和危害。此外,应比较针灸技术和穴位以评估有效性和可行性。