We conducted a randomized controlled trial of methadone maintenance (standard treatment) to chemically dependent hospitalized pregnant women vs. methadone combined with the offer of daily acupuncture treatments. Our primary outcome was the number of days that neonates were treated with morphine for neonatal withdrawal syndrome. We received ethical approval from the University of British Columbia Clinical Ethics Research Board and the BC Women’s Hospital Research Review Committee.
We conducted our study at BC Women’s Hospital in Vancouver, British Columbia between July 15, 2005-April 30, 2008. Chemically dependent women living in Vancouver and surrounding suburbs are referred to the BC Women’s Chemical Dependency Unit by their primary caregiver as soon as they present for prenatal care, usually in the second trimester. They are admitted to the chemical dependency unit on a voluntary basis. They are offered a methadone maintenance program or support to withdraw from methadone and other illicit drugs. After an initial stay of approximately two months, they are discharged then readmitted approximately two weeks prior to their due date. After the birth, mothers and their newborns are discharged together when the baby is stable, gaining weight, and does not require treatment for symptoms of NAS. The unit is built on an empowerment model in which women have access to a variety of “healing” activities such as yoga, gardening, therapeutic touch, peer support groups, arts and crafts, group walks and massage therapy. Residents participate in their own discharge planning meetings. Sessions with alcohol and drug support counsellors are available on the unit. Urine testing is not done. Babies room in with their mothers unless neonatal intensive care is required. All women admitted to the Chemical Dependency Unit at BC Women’s Hospital were offered participation in the current study.
Women admitted to the chemical dependency unit at BC Women’s Hospital, Vancouver, B.C. were considered to be eligible for inclusion. Exclusion criteria consisted of inability to read or write English, having a pacemaker or other electrical implant, having a bleeding disorder, or a condition putting someone at particular risk for infection, including for example, damaged heart valves, diabetes requiring insulin, immunosuppressive drug therapy or open wounds.
Number of days of treatment of the newborn with morphine was chosen as the primary outcome because it is a clinical measure of the time required for the newborn to complete withdrawal from opiates. In this unit, morphine is prescribed for the neonate by pediatricians if there is a constellation of symptoms unresponsive to environmental control including: 1) convulsions, 2) inconsolability or crying continuously for 3 hours, 3) persistent tremors or jitteriness when undisturbed, 4) continuous central nervous system irritability including hyperactive Moro reflex, tremors, jitteriness, increased muscle tone and unprovoked muscle jerks, 5) persistent vomiting or projectile vomiting over a 12 hour period, or 6) explosive diarrhea for 2–3 consecutive episodes . Additional clinical signs such as tachycardia, tachypnea, watery stools, fever, or weight loss > 10% may justify use of morphine after consideration of differential diagnoses. Morphine 1 mg/ml is started at a rate of 0.03 mg/kg/dose every 3 hours. The dose is reviewed daily and titrated based on daily weights and ongoing symptoms.
Secondary neonatal outcomes include gestational age at birth, Apgar scores, days to regain birth weight, rates of admission to a neonatal intensive care nursery, withdrawal symptoms and rates of transfer of the infant to foster care. Infants experiencing NAS have been shown to require significantly longer time to regain their birthweight . Neonatal outcomes were ascertained from the hospital chart by a research assistant blinded to study allocation. Withdrawal symptoms are routinely documented by nurses using a modified version of the Finnegan Scale . Nurses were not formally blinded to study allocation. The Finnegan scale has been widely used in studies of NAS [47, 48] and has been shown to be a valid standard against which pharmacologic treatment can be titrated [49, 50]. The original 22-item-scale instrument consists of variables such as sleep duration after feeding, mottling, and nasal stuffiness. We report on a subset of more objective items that are documented daily on the unit including high pitched cry, inconsolable crying, tremors, muscle tone, sucking and swallowing, vomiting and diarrhea.
Women were recruited on the unit by a trial coordinator. After obtaining written informed consent a sequentially numbered opaque envelope was opened to reveal the study allocation by the study research assistant. Random allocation to study arm was undertaken using statistical software, SPSS version 18.
We used the National Acupuncture Detoxification Association (NADA) five-point auricular acupuncture protocol for treating symptoms of drug withdrawal . The protocol consists of inserting five stainless steel acupuncture needles in both ears at points known as Sympathetic, Shen men, Liver, Kidney, and Lung. This point combination is believed to be specific for substance abuse. The acupuncturist swabbed the ears with alcohol and inserted sterile, disposable needles. Following the 45 minute treatment, participants removed the needles and placed them in protective sharps boxes in order to minimize risk of needlestick injury to the acupuncturist. All needles were counted to ensure that all had been retrieved and disposed of. A sham acupuncture procedure was not used. Chinese traditional medicine does not include the concept of a placebo . Those who argue that auricular acupuncture stimulates the vagus nerve, which innervates the ear concha, state that needles placed anywhere in the concha should produce the same effects . Studies utilizing sham procedures have failed to show a difference between the control and active experimental conditions [51, 53].
Women participating in the treatment group of our study were given access to a quiet room furnished with comfortable reclining chairs. The acupuncturist spent approximately 30 minutes with them each day.
Physicians prescribing morphine to newborns were blinded as to treatment arm. Assignment to trial arm was not written in the chart. Women received acupuncture treatment at mid-day when pediatricians were not usually on the unit and in a room with the door shut. Mothers were asked not to tell physicians if they were receiving acupuncture.
We planned to have 80% power to detect a 30% reduction of days of neonatal morphine treatment, from 11.75 (5.2) to 8.25 days (5.2) with 37 subjects per treatment arm. The baseline rate of 11.75 days was derived from a pilot study of this population at BC Women’s by one of the authors (RA) .
Data analysis was by intention to treat. Outcomes of participants were analyzed within the trial arm that they were randomly assigned to. Socio-demographic characteristics assessed at baseline included age, marital status, ethnicity, income, parity, housing (stable vs. transient), smoking status and education. Pregnancy-related characteristics assessed included pre-pregnant weight and weight gain, month of entry to prenatal care, and self-reported substance use. Tests of normality (Kolmogorov-Smirnov) were applied to continuous variables. Normally distributed continuous variables were compared between groups using the t-test. Non- normally distributed variables were compared using the Mann–Whitney U test for two groups and the Kruskal-Wallis test for three groups. Discrete variables were compared between groups using the chi-square statistic when expected cell counts were greater than five; otherwise the Fisher’s exact test was reported. Statistical analysis was undertaken using SPSS, version 18.