A team at the Medical University of South Carolina is collaborating with Spark Biomedical to develop a better standard of care for babies who are born dependent on opioids.
Every day across the United States, almost 80 newborn babies are diagnosed as going into drug withdrawal because they are no longer getting the drugs their mothers used while pregnant, according to the Centers for Disease Control and Prevention.
With few standard, evidence-based treatments, most hospitals give the babies medications like morphine - itself an opioid - to ease withdrawal symptoms. The neonatal intensive care team must then wean the baby off that prescribed drug over the course of two to three weeks. The novel treatment being tested at MUSC Children's Health uses electrical stimulation to induce the baby's body to produce more of its own opioid-like hormones, better known as endorphins. The idea is that by utilizing these self-produced opioids, the babies can be weaned from the morphine more quickly, reducing potential side effects and decreasing the time the baby must spend in the NICU.
Dorothea Jenkins, M.D., a professor of pediatrics in the College of Medicine who specializes in treating newborns, and Bashar Badran, Ph.D., an assistant professor in the College of Medicine Department of Psychiatry and Behavioral Sciences who specializes in brain stimulation, teamed up, for this trial, with Spark Biomedical, a company that was already developing an over-the-ear neurostimulation device to deliver transcutaneous auricular stimulation (tAN) therapy to adults.
"This neurostimulation is giving the brain a little bit of a boost of its own endogenous opioids to perhaps reduce the need for exogenous morphine, which has all these dangerous side effects when delivered for prolonged periods of time in this critical neurodevelopmental window," Badran said.
"This neurostimulation is giving the brain a little bit of a boost of its own endogenous opioids to perhaps reduce the need for exogenous morphine, which has all these dangerous side effects when delivered for prolonged periods of time in this critical neurodevelopmental window."Bashar Badran, Ph.D.
So far, three babies have received the treatment and were all safely weaned from morphine within 10 days.
"It's really exciting to be able to see a baby organize, calm down, be able to eat and sleep," Jenkins said, adding that's its remarkable to have them look you in the eye and watch you like a typical newborn.
Neonatal abstinence syndrome, also called neonatal opioid withdrawal syndrome (NOWS), increased fivefold from 2004 to 2014, according to the National Institutes of Health. The opioid crisis sweeping the nation has not exempted pregnant women, and babies born dependent on opioids face a painful start to life. The opioid receptors in their brains, meant to be filled by endorphins after nursing or to reduce stress and pain, have instead become accustomed to being constantly filled by heroin, oxycodone or methadone - drugs which leave their bloodstreams after birth, leaving them suffering serious withdrawal symptoms such as trembling, irritability, constant high-pitched crying, sleep problems, seizures, hyperactive reflexes and digestive issues.
"When you see babies who are withdrawing from opioids, you immediately feel terrible for them. They are in a lot of distress. They are jittery, crying constantly, hard to soothe and console, and may have fast breathing and vomiting," Jenkins said.
The obvious relief offered by the tAN therapy has been striking, the researchers said.
"While we have seen success with tAN therapy in our adult opioid withdrawal clinical trial, we weren't sure how this treatment approach would generalize to newborns with NOWS. Now that the trial is underway, the results are beyond our expectations and, most importantly, have improved the lives of the newborns and their families," said Navid Khodaparast, Ph.D., chief science officer at Spark Biomedical.
This isn't the first time that Badran and Jenkins have worked together. Badran is a pioneer in the new procedure of stimulation of the vagus nerve near the ear to improve outcomes, and for the past couple of years, the two have been working on a project to use neurostimulation to help train premature babies to suck and drink from a bottle. Without this skill, many premature babies require surgery to insert a gastrointestinal tube for feeding.
Badran was presenting their work at a conference where he met Dan Powell, CEO of Spark Biomedical, which was already working with adults undergoing opioid withdrawal. Inspired, the two groups decided to combine their expertise to focus on the most vulnerable population affected by opioid use.
They were awarded a $217,000 Small Business Innovation Research grant from the National Institutes of Health HEAL Initiative to conduct a small pilot trial at the MUSC Shawn Jenkins Children's Hospital and Pearl Tourville Women's Pavilion. In the pilot, all eligible infants receive the neurostimulation treatment. If the results continue to look promising, then the two organizations can apply for an additional NIH grant to conduct a more extensive, controlled, double-blind clinical trial.
The treatment works like this: The care providers at MUSC Health already use a standardized assessment tool, called the Finnegan scale, to assess babies' withdrawal symptoms. The Finnegan score guides the care providers in determining how much morphine to administer. During the trial, however, the neurostimulation is administered first, for 30 minutes. The tAN device, called the Roo, delivers gentle electrical stimulation to cranial nerve branches on and around the newborn's ear. It's believed that tAN activates specific brain regions to signal the release of endorphins, which bind to the vacant opioid receptors and ease the withdrawal symptoms. After the therapy, the baby is reassessed on the Finnegan scale. The neurostimulation should have caused the baby's Finnegan score to decrease, and, if this is consistent over 12 hours, the amount of morphine given is decreased.
They weaned two of the babies off morphine in eight days, Jenkins said. Her records of past opioid-dependent babies indicate that there's only about a 10% chance a baby would be weaned in a week after starting on high-dose morphine.
"This open-label clinical trial is designed to show that a seven- to 10-day morphine wean is safe and achievable with tAN, which would be a significant improvement over standard of care," Jenkins said. "With three infants successfully completing the protocol, we are encouraged that this therapy may offer benefit."
Although this trial is focused on babies born dependent on opioids, other babies can develop dependency when given morphine during their stays in the NICU. Those babies are typically "very, very sick," Jenkins said, and need morphine because they are in pain or need to be ventilated. They receive a continuous supply of morphine, sometimes for weeks, and doctors must carefully wean them off the drug after they're well. These babies would also be good candidates for this treatment, she said.
With the increase in babies born opioid dependent, Level II hospital nurseries across the state are caring for these little patients in addition to NICUs, Jenkins said. It would be great, she said, to have an easy-to-use portable device that any hospital could use to help these babies.
