Norwegian health professionals disagree on whether pregnant women in opiate maintenance treatment (OMT) should have the OMT drug (methadone or buprenorphine) tapered or whether they should continue with OMT. We have summarised the evidence on effects for mother and child of tapering compared with continued maintenance treatment during pregnancy.
· We found three small (total N = 292) controlled cohort studies of low-methodological quality.
· The studies included outcomes for the new-born children (occurrence of neonatal abstinence syndrome (NAS), NAS treatment and premature births, duration of treatment, Finnegan score, Apgar score, birth weight, length, head circumference and gestational age), and for the pregnant women (drug use and smoking) .
· For each outcome, the effect estimate indicated more than one possible effect of tapering: benefit, harm or no effect compared to unchanged or increased dose.
· None of the included studies carried out long-term follow-ups mothers and children over time.
Conclusion: The evidence is too uncertain to determine whether there is a difference in effect between tapering and unchanged or increased dose on neonatal outcomes, or on drug use and smoking in pregnant women in OMT. Future studies should have sufficiently large sample sizes, use controlled and prospective study designs, report all relevant outcomes, and also report long-term follow-up of women and children.
Maintenance therapy with long-acting opioids (either methadone or buprenorphine) is an important part of opioid maintenance treatment (OMT). The purpose of OMT is to compose a comprehensive rehabilitation course for people with opiate dependence syndrome.
In Norway, approximately 30 out of 2300 female OMT patients give birth to children every year. The use of OMT drugs during pregnancy leads to withdrawal symptoms in about half of the new-borns. The withdrawal symptoms are transient, and long-term effects on the child are unclear. Tapering of OMT drugs implies a risk of increased stress in both women and foetuses, substance use and overdose in women, and potentially severe withdrawal symptoms in the foetus.
Published in 2011, existing national clinical guidelines for pregnant women in OMT recommend, like the international guidelines, continued maintenance doses of buprenorphine or methadone. The recommendations for continued maintenance treatment are among those to be reviewed in the pending revision of Norwegian guidelines. The revision is largely based on a disagreement among Norwegian health-professionals about whether there are benefits of maintenance treatment for pregnant women that outweigh possible harms to the child.
The Norwegian Directorate of Health has commissioned the Norwegian Institute of Public Health to conduct a systematic review with the following research questions:
- What are the effects on mother and child of tapering from methadone or buprenorphine compared to continued OMT during pregnancy?
- What is the prognosis for mother and child when the OMT drug is tapered during pregnancy?
In May 2018, we searched for systematic reviews and primary studies in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PycINFO, CINAHL, Cochrane Database of Systematic Reviews and Epistemonikos. In addition, we reviewed the list of included studies in a Norwegian report from 2017 with a similar topic.
Two researchers screened search hits, selected studies and assessed methodical quality (risk of systematic bias) in all included studies. We extracted data from all included studies and presented them in tables. Wherever possible, we pooled results from several studies in meta-analyses. We assessed our confidence in each effect estimate using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool.
The literature search yielded in 1,358 hits after de-duplication. Of these, we directly excluded 1294 irrelevant studies that clearly did not meet our inclusion criteria. We assessed 80 articles in full text, of which we excluded 77.
We included three studies that compared the effect of tapering versus unchanged or increased dose in women who were in OMT when they became pregnant. We did not identify any studies that could answer our prognostic question.
The three included studies were cohort studies; one prospective, one retrospective and one with both prospective and retrospective design. The studies took place in Ireland, the United States and Norway, respectively. A total of 292 pregnant women in OMT, and their exposed children, participated in the three studies. None of the studies examined long-term effects of tapering on the children.
We assessed the methodological quality of all three studies as low. This, as well as weak study design, small sample sizes, and great uncertainty around the effect estimates, contributed to our consistently very low confidence in the results. Consequently, we do not report numerical results in this summary.
The studies included outcomes in new-borns (prevalence of neonatal abstinence syndrome (NAS), NAS treatment and premature birth, and treatment duration, Finnegan score, Apgar score, birth weight, length, head circumference and gestational age) and in women (substance use and smoking). For all outcomes, apart from one, the effect estimates and confidence intervals showed more than one possible effect of tapering: beneficial, harmful or the no difference as compared to unchanged or increased dose. The effect estimate for smoking at the end of pregnancy implied that a smaller proportion of women in the tapering group, or that a similar proportion of women in the two groups, report smoking.
One of the strengths with this systematic review is that our inclusion criteria embraced studies that are not designed for research questions of effects. It is nevertheless important to emphasise the limitations with such study designs. Small, methodically weak observational studies provide a significant risk of systematic biases in the results. This makes it difficult to conclude about the effect one can expect from tapering of OMT drugs during pregnancy versus continuing treatment with unchanged or increased dose. It is therefore necessary to see the findings in conjunction with experience-based clinical knowledge, user knowledge and context before a decision to change the policy.
None of the included studies examined measures such as low versus high maintenance doses, tapering until discontinuation of drug treatment, or compulsive interventions among pregnant women in OMT. We found no studies that included foetal outcomes or any long-term outcomes for mother and child. The included studies failed to report a number of the individual outcomes that we were interested. Nor did we find any studies of the prognosis for pregnant women who taper the methadone or buprenorphine dose.
In order to provide useful, evidence-based conclusions about the effects of tapering, future studies should have a sufficiently large sample sizes, well-performed controlled, prospective studies, long-term follow-up of mother and child, and relevant outcomes.
The evidence is too uncertain to determine whether there are any differences in the effects on neonatal outcomes between tapering and unchanged or increased dose. It is also uncertain whether tapering lead to more or less substance use and smoking among pregnant women in OMT, compared to unchanged or increased dose. Very low confidence in the effect estimates does not imply that a difference in effect between the interventions is unlikely, but that the direction of a possible effect is very uncertain. Thus, we can neither rule out nor conclude that tapering lead to better, worse or similar effects compared to unchanged or increased doses in any of the outcomes of the included studies.