Acupuncture for neonatal abstinence syndrome in newborn infants.

Background: 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.

Objectives: 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.

Search methods: 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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; I² = 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.