Posts Tagged ‘neonatal abstinence syndrome’

New Treatment for Neonatal Abstinence Syndrome

 

 

 

 

 

 

 

 

 

 

The June 15, 2017 issue of the New England Journal of Medicine contained an article of great interest. Written by Kraft et al., this article titled, “Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome,” described a study comparing buprenorphine with morphine solution to treat opioid withdrawal in the newborn. This study showed significantly shorter duration of treatment and shorter median length of hospitalization for babies with neonatal abstinence syndrome when treated with sublingual buprenorphine compared to traditional treatment with morphine oral solution.

This study covers a hot topic. Many people are alarmed at the rising rate of NAS in our nation’s hospitals. The incidence of NAS has risen four-fold from 2003 to 2012, and cost $316 million in care for those babies just in 2012. [1] Any new treatment that can reduce the duration of withdrawal in newborns, and thus reduce treatment costs and parental anxiety, is an exciting new development.

The NEJM study described was done at Thomas Jefferson University in Philadelphia, Pennsylvania, with subjects enrolled from late 2011 until mid-2016. To qualify for the study, the babies had to be born full-term, defined as more than 37 weeks of gestation, and had to have been exposed to opioids during the pregnancy. The infants had to have signs and symptoms of neonatal abstinence syndrome (NAS), and parental consent to participate in the study.

The study, abbreviated BBORN, for “blinded buprenorphine or neonatal morphine solution,” excluded babies with low birth weight, exposure to benzodiazepines within 30 days of delivery, or serious other medical conditions. For the first part of patient enrollment, breast fed babies were excluded, but this restriction was lifted by 2013, with the national trend of that encouraged these mothers to breast feed. Nearly all of the mothers were on methadone maintenance, with doses ranging from 25 to 265 in the group assigned to buprenorphine treatment, and 30-260 in the group assigned to morphine oral solution, regarded as treatment as usual.

The design of this study was very strong, since it was doubly blinded, which means the providers caring for these infants didn’t know which were randomized to buprenorphine and which were randomized to morphine.

This double-blind approach is important in general, but especially important when dealing with the evaluation of babies in withdrawal. Sometimes nurses and other medical professionals who are evaluating withdrawal in babies have an emotional reactions. Some of these people can overestimate the degree of withdrawal, leading to longer hospitalization and over-medication.

If you are wondering “How do they get the babies to keep the medication under their tongue?” I wondered the same thing. The study explained that after getting a buprenorphine dose (or placebo, if their active drug was morphine solution), the babies were given a pacifier to extend the time the medication is in contact with the sublingual mucosa.

How clever. When my cat Yoshi was prescribed buprenorphine for urethritis, I had to dose him with buprenorphine, but there’s no way he kept it under his tongue. I thought some had to have gotten absorbed just from the oral mucosa. He definitely had a response to the medication, being opioid-naïve…he fell asleep, which gave him respite from frantic over-grooming of his urethra…

But I digress.

Anyway, this study showed buprenorphine significant decreased the duration of treatment for NAS, by an average of thirteen days, with no increase in adverse events, as compared to treatment as usual with morphine oral solution. The study authors postulate that the long half-life of buprenorphine levels the peaks and troughs seen with the shorter-acting morphine solution.

The study was limited by its small sample size. The authors wanted to get at least 40 subjects in each treatment arm, but had a hard time recruiting parents willing to enter their newborn into a treatment trial. They ended up with 30 patients in the buprenorphine treatment arm, and 28 in the morphine treatment as usual arm.

I can only imagine how hard it was to convince nervous mothers-to-be to enter their babies in this study. They were likely already worried about NAS in their infants, and perhaps feeling guilty about being pregnant while having the disease of opioid use disorder. Asking a mom – or dad – to then enroll in a study using a new medication (new for this use, at least) would be a hard sell.

Thankfully even with fewer test subjects than desired, the data still reached statistical significance. If future studies can replicate these outcomes, we will have a new medication with which to treat NAS, which will reduce the length of stay in the hospital for babies, reduce medical costs, and get these babies home sooner.

  1. Corr et al., “The Economic Burden of Neonatal Abstinence Syndrome in the United States,” Addiction, 6/13/17 http://onlinelibrary.wiley.com/doi/10.1111/add.13842/abstract
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The “Protect Our Infants Act”

Rate of neonatal abstinence syndrome per 1,000 live births, by mother's county of residence

Rate of neonatal abstinence syndrome per 1,000 live births, by mother’s county of residence

(This map can be seen at:http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6405a4.htm )

I just read an interesting news piece about new legislature named “Protecting Our Infants Act.” This bill was sponsored last year by Rep. Katherine Clark of Massachusetts, but died during the session. Then she got support from other congressmen, including Rep. Steve Stivers from Ohio (who happens to represent the area of the country where I was raised, in Southeastern Ohio), and Sen. Bob Casey of Pennsylvania. When Majority leader Senator McConnell got onboard as a sponsor of the bill this year, it gained momentum, and is now in a congressional committee, waiting to be sent to the house or Senate.

When I first heard about this new bill, and that Senator McConnell was backing it, I worried it might be something weird and unscientific that would send us backward in time. But after reading the bill online for myself, I’m in favor of it: https://www.congress.gov/bill/113th-congress/senate-bill/2722/text

This bill asks the Secretary of Health and Human Services to collect and evaluate all of the best evidence-based information available about how to prevent and treat babies born dependent on opioids. The bill’s actual wording is that the secretary of HHS “shall conduct a study and develop recommendations for preventing and treating prenatal opioid abuse and neonatal abstinence syndrome, soliciting input from nongovernmental entities, including organizations representing patients, health care providers, hospitals, other treatment facilities and other entities, as appropriate.”

The bill asks for Health and Human Services to identify and also report on any gaps in our knowledge, where more research is needed. The bill also requests an evaluation of medical use of opioids during pregnancy, and an assessment regarding access to treatment for opioid-addicted pregnant women and post-partum women. The bill asks for an evaluation of the risk factors for opioid addiction, and the barriers to treatment.

According to the bill, the Secretary of Health and Human Services will collect all this information and post it on a website, available healthcare providers in the U.S., in no less than one year after the bill (hopefully) passes.

Our present Secretary of Health and Human services is Sylvia Mathews Burwell, who replaced Kathleen Sibelius last summer. I didn’t know much about her, so I went to the website for HHS, and found a blog post of hers, addressing our epidemic of opioid addiction: http://www.hhs.gov/blog/2015/03/26/its-time-act-reduce-opioid-related-injuries-deaths.html

I really like what I read. In her blog post, she emphasizes three areas which need attention: wider distribution of naloxone to prevent opioid overdose deaths, better prescribing practices by doctors, and…“using medication-assisted treatment to slowly move people out of opioid addiction.”

What a relief. She supports MAT. I mean, one would hope and expect such support for evidence-based treatments, but as my readers know, sometimes politicians take strong positions on matters about which they know little (oh yes I’m talking about Tennessee).

If the Secretary does a good job, this is a golden opportunity to promote evidence-based treatment of opioid addiction in pregnancy: MAT.

I also think some politicians could learn things they didn’t expect.

Is it possible that with such a prominent seal of approval, both methadone and buprenorphine treatment of opioid addiction will move out of the dark ages? Perhaps politicians will say, “Oh I now see I don’t know what I’m talking about when I limit access to treatment at methadone and buprenorphine programs! How foolish of me!”

Is it possible that someday in the future I’m going to call a certain obstetrician in my area about the methadone dose of a patient we both treat, and he will say, as he’s said before, “It’s wrong to treat pregnant patients with methadone. You need to get them off that stuff!”

And I will say…please go to the Health and Human Services website, to read what the experts say, since you won’t believe me. And he will read. And he will change his mind. He will begin to encourage all his opioid-addicted patients to seek effective, evidence-based treatment… And the health of the whole community will improve as we come to agree on evidence-based solutions to medical problems.

So my first train of thought was a happy engine, chugging along with optimism and relief. Then came the caboose of negativity.

Why do doctors need to have the Secretary of Health and Human Services research this issue for them? For prevention, yes, that’s a public health issue and more research would be valuable. But to find out how to treat a medical issue?? If doctors have a question about how to deal with a medical issue, we have sources that summarize and review best data to date. We go to a reliable source, to the experts in the field. For the topic of opioid addiction in pregnancy, one would ask obstetricians and addiction medicine doctors.

Oh wait. The American College of Obstetrics and Gynecology, along with the American Society of Addiction Medicine, already have published a position paper of best practices in this area. It is titled, “Opioid Abuse, Dependence, and Addiction in Pregnancy.” They didn’t hide their report in a dark cave. They published it. They posted it on the internet:

In fact, if you Google “pregnancy and opioid addiction,” one of the first options is ACOG’s paper: http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/Opioid-Abuse-Dependence-and-Addiction-in-Pregnancy
And for those people who are deeply puzzled by how to treat opioid addiction in pregnancy, this is the summary sentence of the report, published in 2012: “The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered.”

That wasn’t so hard, was it?

Then I Googled “american academy of pediatrics and neonatal abstinence syndrome,” because I figure who knows kids better than pediatricians, and my first choice was a state of the art review article from 2014 describing NAS and its treatment in detail.

After considering the “Protecting our Infants Act,” I have several observations. First, it’s not terribly hard to find state of the art information about the treatment of opioid addiction in pregnancy, and the treatment of neonatal abstinence syndrome, if the healthcare worker really wants to find it. But if the healthcare worker can’t or won’t accept these answers due to ideology, a report from the Secretary of HHS may carry more weight than the science that’s already available.

I also believe we have a whole lot more to learn in this field. This new Act’s best feature is the mandate to assess areas where we need more research, and to investigate barriers to treatment, because there are many. For example, Eastern Tennessee has one of the highest rates of NAS in all the country, yet that state denied a certificate of need for a methadone clinic to be established to serve that area. I do believe that history will judge those politicians harshly.

I hope the bill passes. It would be interesting to see what the Act’s current sponsor, Senator Mitch McConnell, would think about the DHH report.