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PAS 2017: New Approaches Help Babies with Opioid Withdrawal Syndrome


Letting mothers and babies room together and using methadone or buprenorphine instead of morphine to manage withdrawal symptoms leads to shorter stays and other benefits for newborns with neonatal abstinence syndrome (NAS), according to several presentations at the Pediatric Academic Societies Meeting this month in San Francisco.

Infants who experience drug withdrawal after birth is a growing public health problem related to the ongoing opioid epidemic in the U.S. The number of newborns exposed to opioids during gestation has increased 5-fold over the past 2 decades and may be a factor in as many as 5 per 1,000 births, according to Elisha Wachman from Boston Medical Center.

According to the American Academy of Pediatrics, the first-line therapy for babies with NAS is non-pharmacologic supportive care. If this is not adequate, infants are typically treated with tapering doses of morphine, sometimes in a neonatal intensive care unit (NICU). One recent study found that more than 80% of infants with NAS received pharmacologic therapy.

But newer approaches to evaluating, treating, and managing NAS can lead to better outcomes including fewer NICU admissions, shorter hospital stays, less opioid exposure for babies, and lower cost.

Matthew Lipshaw from Yale-New Haven Children’s Hospital and colleagues evaluated whether a simple assessment of an infant's ability to eat, sleep for at least an hour, and be consoled within 10 minutes -- dubbed "ESC" -- could be used instead of the more complex Finnegan Neonatal Abstinence Scoring System (FNASS), which assigns a numerical score based on nearly two dozen factors including excessive crying, sweating, tremors, and other physical symptoms.

In a retrospective review of 50 infants, the ESC approach led to 6 babies (12%) starting morphine, compared to 31 infants (62%) who would have been eligible based on FNASS scores. The average length of hospital stay fell to 6 days using ESC, down from 23 days using FNASS.

Wachman reported on a quality improvement initiative at Boston Medical Center's RESPECT perinatal program that aimed to reduce pharmacologic treatment for NAS, shorten hospital stays, and increase breastfeeding.

The program uses a "rooming-in" model with mothers and infants staying together in the same room. Staff and patients were educated about the benefits of supportive care measures such as skin-to-skin contact, breastfeeding on demand, swaddling, and a quiet, low-light environment. Infants were not given pharmacologic therapy during the first 24 hours after birth, but if they needed it after that they received methadone every 8 hours.

Before the initiative, 82% of newborns with NAS received pharmacologic treatment (usually with morphine) and 34% required adjunct medications such as phenobarbital.The average length of stay was 19 days, 36% of infants were breastfed, and the average cost of treatment was $38,900.

Among the 59 infants treated under the new protocols, pharmacologic treatment decreased to 42%, no infants needed adjunctive medications, the mean length of stay fell to 11 days, 59% were breastfed, and the average cost was cut in half.

The program has now adopted the ESC approach and introduced "cuddlers" to soothe babies if parents are not available. These additional measures will be evaluated in a future analysis.

"We basically accept the fact that the infants have withdrawal symptoms. We don't quantify it; what we look at is how is the baby doing -- are they doing what a baby is supposed to do?" Wachman said. "If they're not doing those things, then we up their medications. Before we were treating the numbers, now we're treating the baby."

In a related presentation, Kathryn MacMillan from Dartmouth-Hitchcock Medical Center described findings from a systematic review and meta-analysis of rooming-in during NAS treatment.

A medical literature database searchidentified 6 relevant studies that together included a total of 549 infants. These studies consistently showed that rooming-in reduced the use of pharmacologic therapy, shortened length of stay by an average of 10 days, and lowered inpatient cost by around $15,000.

Pharmacologic Therapy

Even with improved supportive care, some infants still require pharmacologic therapy for NAS. The AAP has given its approval to both morphine and methadone until more definitive comparative data are available. Buprenorphine, a newer drug used for adult opioid substitution treatment, may also have a role to play.

Veeral Tolia from Baylor University Medical Center presented findings from an analysis comparing morphine and methadone for NAS treatment. Looking at data from the Pediatrix Clinical Data Warehouse from 2011-2015, which covers 20% of U.S. NICU admissions, they identified 7775 infants who received pharmacologic therapy using either morphine (84%) or methadone (16%).

Methadone treatment was associated with a shorter total length of stay compared to morphine (median 19 vs 23 days) as well as less time in the NICU (median 18 vs 21 days). Methadone-treated infants were also much less likely to need adjunct medications.

Walter Kraft from Thomas Jefferson University in Philadelphia presented findings from the BBORN study, a Phase 3 clinical trial comparing NAS treatment using sublingual buprenorphine or oral morphine. (Simultaneously published in the New England Journal of Medicine.)

The study included 63 full-term infants exposed to opioids, mostly methadone, during gestation. They were randomly assigned to receive a starting dose of 5.3 mcg/kg/day buprenorphine given every 8 hours, or 0.07 mg/kg/day morphine given every 4 hours. Doses could be adjusted upward if needed. Once infants were stabilized, they were weaned off the drugs in 10% increments.

Infants treated with buprenorphine had significantly shorter hospital stays (median 21 vs 33 days) and a shorter total length of treatment (median 15 vs 28 days) than those treated with morphine. Weight gain was comparable in the 2 groups and a similar proportion of babies required supplemental phenobarbital. Both treatments appeared equally safe, with no drug-related serious adverse events in either study arm.

"This study has large public health implications, since the rate of neonatal abstinence has increased almost five-fold over the past 15 years," Kraft said in a statement. "Our findings provide evidence that buprenorphine can safely and effectively serve to reduce the significant burden of neonatal abstinence syndrome on individual infants and families and hospitals."



M Lipshaw, et al. A Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome.Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 2315-2.

E Wachman, D Schiff, B Philipp, et al. Reducing Length of Hospitalization for Neonatal Abstinence Syndrome through Non-Pharmacologic Care and Methadone: A Quality Improvement Project. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 3715.4.

K MacMillan, C Rendn, K Verma, et al. Rooming-in Reduces Medication Use and Length of Stay in Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 2315.8.

V Tolia, K Murphy, M Bennett, et al. Treatment for Neonatal Abstinence Syndrome with Methadone Was Associated with a Shorter Length of Stay vs. Treatment with Morphine in Large, National, Multi-center Cohort of Infants. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 4615.4.

W Kraft, I Chervoneva, K Kaltenbach, et al. A Randomized Controlled Trial of Sublingual Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. Pediatric Academic Societies Meeting. San Francisco, May 6-9, 2017. Abstract 2195.4.