As someone with an interest in neonatal abstinence (NAS) I am surprised that I missed this study back in May. Anyone who says they aren’t interested in NAS research must be turning a blind eye to the North American epidemic of patients filling neonatal units or postpartum wards in need of treatment for the same. News feeds such as CNN have covered this story many times with concerning articles such as this published “Opioid Crisis Fast Facts” even the Trump White House has officially declared it as an emergency at this point. With NICU resources stretched and care providers fatigue levels wearing thin (these patients are typically very challenging to take care of due to the crying and agitation with neurological excitability that is at the core of the symptoms, something needs to be done. The vast majority of neonatal care providers treat such patients with an approach that promotes first non pharmacologic strategies such as keeping mom and baby together when possible, breast feeding and disturbing these infants as little as possible to name a few points. For those patients though who require pharmacologic support though, the mainstay has been oral morphine. At least in our units though once a patient is admitted and undergoes treatment we are still looking at anywhere from 3-4 weeks on average that they will occupy a hospital bed. If only there was a better way.
Could Buprenorphine do the trick?
While morphine is widely used to treat NAS symptoms unresponsive to other non pharmacologic methods of control, buprenorphine has a similar profile as an opioid but has less risk of respiratory depression as a partial agonist. A small but important trial has been published directly comparing the use of morphine to buprenorphine for treatment of NAS symptoms with the primary outcome being days of treatment and the second important point being length of stay. The trial, Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome.by Kraft WK et al was entitled the BBORN trial for short. This was a single centre trial in which a double blind/double dummy approach was used. By double dummy this meant that after randomization those babies randomized to morphine received morphine plus a buprenorphine placebo and the other arm received a buprenorphine dose and a morphine placebo. In total 33 infants were randomized to buprenorphine and 30 to morphine (hence my comment about this being a small study). Their power calculation had called for 40 infants per arm to detect a 28% difference in the primary end point of duration of treatment but in the end that didn’t matter so much as they found a significant difference exceeding their estimate anyway. A lack of power would have become important mind you had they not found a difference as they wouldn’t have actually had the numbers to do so.
A strength of the study up front was that all care providers scored NAS symptoms the same way (need to take into account there is some subjectivity in scoring altogether though) and escalations and decreases of medication were done following a strict protocol both ways. In both arms, once a maximal dose of 60 mcg/kg of body weight for buprenorphine and 1.2 mg/kg for morphine was reached phenobarbital was added. When comparing the two groups at the outset there were no significant differences in characteristics so two generally similar populations of infants were being treated.
The Results Were Indeed Impressive
Before launching into the table, there were 21 babies in both groups that were bottle fed and 12 in the burprenorphine group and 9 in the morphine group that breastfed.
Outcome | Buprenorphine | Morphine | p |
Median days of treatment | 15 (3-67) | 28 (13-67) | <0.001 |
Bottle feeding | 15 (3-67) | 28 (13-67) | |
Breast feeding | 20 (3-55) | 28 (16-52) | |
Hospital stay in days | 21 (7-71) | 33 (18-70) | <0.001 |
Bottle feeding | 21 (7-71) | 33 (18-70) | |
Breast feeding | 26 (7-58) | 32 (20-58) |
No difference was seen in those who needed phenobarbital. Looking at the table, a couple things really stand out to me. They were looking for a 28% reduction in days of treatment. The results came in far excess of that at a 46% reduction. Curiously, breastfeeding which has classically been associated with a reduction in scores and therefore faster weaning due to less symptoms seemed to have the opposite effect here. Does this imply that breastfeeding slows down both duration of treatment and length of stay as a result? With a study this small it is difficult to say with so few breastfed babies but if I had to guess I would suggest those mothers that worked at breastfeeding may have had longer stays.
Should we all jump on the buprenorphine train?
For now I would give this a big maybe. One of the concerns about burprenorphine is that it comes as a solution of 30% alcohol. Giving multiple doses (3 per day in this study) of such a solution could in part contribute to these results of lower NAS symptoms. Is giving alcohol to reduce symptoms a good idea here? Not sure if there are any long term effects and moreover if the cumulative dose of this medication would be of a concern. Definitely something to check with your local pharmacist before rolling this out. On the other hand if the dose of alcohol provided was truly significant I might have expected the burprenorphine group to be poorer feeders due to intoxication which we certainly did not see.
With increasing volumes of newborns afflicted with symptoms of NAS we do need to find a way to stem the tide. Ideally, primary preventative strategies would be best but until that solution is found could burprenorphine be the next step in tackling this epidemic?
Thank you for bringing this important subject. Certainly interesting finding and worth trying especially with the less side effects.
Keeping mothers with their babies definitely helps
Wow this sounds good. I am an RN who works in Ontario. We have an 8 bed ward and half are filled with NAS children for 3-4 weeks. Leaving the other four beds for preemies or other babies. The cost of having these babies and their families in hospital is alarming. The public isn’t aware of this epidemic. For me it’s what can we do to help these babies from suffering less and as a previous lactation consultant and present nicu nurse, no to breastfeeding unless we can test the breastmilk for substances . People lie and these babies have prolonged withdrawal and there have been cases, at least one , in the US where baby was receiving morphine and mom was taking codeine and more substances , baby received too many opioids with breastfeeding. We need to be careful as healthcare givers that we protect the infant .
I agree with Ellie. Unless we as care givers can find a way to measure the amount of any & all substances in Mom’s breastmilk, we have no way of knowing whether the infants scores are real & therefore how do we titrate the medication(s)? We don’t want the infant to suffer through withdrawal; on the other hand, we don’t want to overdose him/her either.