Effects of opioid agonist treatment for pregnant opioid dependent women( 10.12.2008 )
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Background: The Norwegian Directorate of Health commissioned the Norwegian Knowledge Centre for the Health Services (NOKC) to do a review about the effects of opioid agonist treatment for pregnant opioid dependent women. The review would help answer the question of whether and how opioid dependence in pregnant women should be managed with the opioid agonists methadone and buprenorphine. The issue to be addressed was what kind of treatment effects methadone and buprenorphine medication caused during pregnancy on mother and child, compared to other or no treatment. We examined four effect questions: (1) Different dose levels of methadone; (2) Standard methadone maintenance treatment (MMT) versus enhanced MMT; (3) MMT versus other opioid agonist treatment (buprenorphine, slow-release morphine, Natrexone implant treatment (NIT)); (4) MMT versus no medical maintenance treatment. We focused on the effects of such treatments on the opioid dependent women and their children.
Methods: In June 2007, we searched systematically for relevant literature in international scientific databases, selected studies according to pre-set criteria, appraised the methodological quality using checklists, and summarised the results in tables and in meta-analyses. We analysed the studies according to the four above mentioned foci.
Results: We included and summarised results from a total of 30 studies; four randomised controlled trials, one non-randomised clinical control trial and 25 non-randomised effect evaluations. Most studies were of medium or low quality and GRADE showed that the quality of the evidence was very low or low for all outcomes. With respect to dose level, there were too few studies and they were too heterogenous for us to perform any meta-analysis. This was true also for the question of standard versus enhanced MMT. With respect to the question of effect differences between MMT and buprenorphine, the meta-analysis showed that treatment with buprenorphine resulted in more mothers keeping custody of their children. However, GRADE documented very low quality for this outcome. According to our meta-analysis, methadone resulted in significantly fewer incidences of Neonatal Abstinence Syndrome (NAS) compared to slow-release morphine, but GRADE showed very low quality for this outcome. Lastly, with respect to effect differences between MMT and no medical maintenance treatment the meta-analyses showed that there were more cases of NAS among newborns of mothers receiving MMT compared to newborns of mothers receiving no treatment, and a longer treatment period was needed for these babies. However, women receiving MMT reported more prenatal visits, gave birth to babies with higher birth weight and gestation age, and these women were more likely to keep custody of their child compared to women receiving no treatment. GRADE showed very low quality for these outcomes.
Conclusion: The evidence base in this review was of very low quality and several questions could not be adequately answered. The current evidence base is insufficient to draw conclusions regarding the differential effects of various methadone dosages and standard versus enhanced MMT. Our meta-analyses suggested that there is an increased risk of NAS among newborns of mothers receiving MMT, and a longer treatment period is required. On the other hand, MMT led to some positive outcomes such as higher birth weight and parental custody. The evidence base included in this review was of low quality and the results are therefore tentative. There is an urgent need for more studies of high quality on the effects of medical maintenance treatment for opioid dependent pregnant women.