This week and next I'll be comparing and contrasting two very different types of studies for advancing the treatment of neonatal abstinence syndrome. This first one is a classic randomized controlled trial (RCT) published in the New England Journal of Medicine.
Source: Kraft WK, Adeniyi-Jones SC, Chervoneva I, et al. Buprenorphine for the treatment of the neonatal abstinence syndrome. N Engl J Med. 2017;376(24):2341-2348; doi:10.1056/NEJMoa1614835. See AAP Grand Rounds commentary by Dr. Jonathan Mintzer (subscription required).
Investigators at a single institution enrolled 63 term infants with in utero opioid exposure and signs of neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine for the treatment of the withdrawal symptoms. The study design was very tight, an RCT with "double-dummy" blinding. (I hate the term double-dummy, why not just say double-placebo to indicate placebos were used for the active drug not being administered to a particular group?) They found significantly shorter duration of treatment needed (median 15 versus 28 days) and length of hospitalization (median 21 days versus 33 days) for the group receiving buprenorphine.
The study has a few blips in that the design changed after the study began, first to eliminate breastfeeding as an exclusionary criterion (they couldn't enroll enough patients because of that), then to make a change in how rapidly the morphine dose was increased (due to change in standard practice), and finally to stop the study earlier than the planned 80 patient enrollment due to overall slow enrollment (the study still took 4.5 years to complete). I don't see any of these as major factors affecting the overall conclusions.
In my pediatric training and early practice, I saw far too many newborns suffering withdrawal symptoms from maternal opioid addiction, mostly heroin in those days. It's so sad to see this syndrome return with our current opioid epidemic. This excellent study is a major contribution to the treatment of neonatal opioid withdrawal, with the only caveats being, as the investigators themselves acknowledge, the small sample size, the lack of inclusion of preterm infants, and the use of only a single institution, which could limit generalizability.
Keep this study in mind for next week's blog, where I'll discuss a very different approach to the same problem, published in Pediatrics.