Infants born to mothers who are in treatment for opioid use disorders with methadone are sometimes born with neonatal abstinence syndrome (NAS), a constellation of symptoms associated with opioid withdrawal. The old way of treating these infants — and the current way in many institutions — is to put them in the neonatal intensive care unit (NICU) and treat them with gradually decreasing doses of morphine. But keep out of the NICU, standardize nonpharmacologic care and empower parents, and what do you get? A reduction in the percentage of infants treated with morphine from 98 percent to 14 percent, a reduction in average length of stay (ALOS) from 22.4 to 5.9 days and a decrease in costs from $44,824 to $10,289. That is what researchers at Yale New Haven Children’s Hospital discovered when they implemented novel “plan-do-study-act” cycles in 2010 in response to a dramatic increase in the number of infants born there who had been exposed to methadone in utero (a 74 percent increase from 2003 to 2009).

The goal was to reduce the ALOS by 50 percent — a goal the interventions far exceeded.

There were 287 methadone-exposed infants in the study, including 55 from the baseline period (2008 to 2010) and 44 from the post-implementation period (2015 to 2016). There were no adverse events, and no infants were readmitted for treatment of NAS.

Other institutions had successfully reduced ALOS after implementing a weaning protocol for morphine and standardizing the scoring of the Finnegan Neonatal Abstinence Scoring System (FNASS), which assigns a numerical score to 21 subjective clinical signs of NAS. It is usually used in an NICU, but there is no evidence that infants with NAS require management in an NICU, and in fact, it makes rooming-in out of the question, which itself is a nonpharmacologic intervention for NAS.

The researchers at Yale “set out to change the paradigm of how we approached the management of infants with NAS,” decreasing ALOS by not using morphine. They used the interventions with all infants with NAS, but only analyzed results for those born at least 35 weeks’ gestation and whose mothers took methadone daily for at least one month before delivery, because they “considered this population to be the most likely to develop signs of withdrawal.” Infants with significant comorbidities were excluded.

During the pre-intervention period, all infants at risk for NAS were admitted directly to the NICU after birth, and infants were monitored using the FNASS. Infants were initially managed in the NICU, with those with scores justifying medication getting morphine. Then, at the discretion of the neonatologist, they were either discharged or transferred to the inpatient unit. At day 5 of life, infants who received no morphine were discharged; infants receiving morphine were discharged one day after the medication was stopped. The second year of the pre-intervention period, the researchers noted an increase in the number of infants with NAS and identified four key drivers that could reduce ALOS: nonpharmacologic interventions, simplified assessment of infants, decreased use of morphine and communication between units.

The interventions

Over the next five years, the researchers developed and implemented eight interventions aimed at reducing the ALOS of infants with NAS.

  • Standardized nonpharmacologic care
  • Prenatal counseling of parents
  • Transfer from well-baby nursery (WBN) to the inpatient unit (with the mother)
  • Development of novel approach to assessment
  • Morphine given as needed
  • Empowering messaging to parents
  • Spread of change concepts to NICU

Nonpharmacologic interventions: Nonpharmacologic interventions included being placed in a low-stimulation environment with dimmed lights, muted televisions and reduced noise. Parents were continuously available to their infants; parents were strongly encouraged to room-in, to feed their infants on demand and to tend to their infant if crying. Staff were trained to view nonpharmacologic interventions as equivalent to medications — “when increased intervention was warranted, the approach was to increase the involvement of the parents before using pharmacologic treatment.” In conjunction with the well-baby nursery, clinicians encouraged breast-milk feeding of all infants for whom there were no contraindications (illicit drug use or HIV).

Prenatal counseling: The parents were given informational handouts several weeks before delivery, and told that they would be expected to stay with their infant throughout hospitalization. They were also able to ask questions, which the outpatient care coordinator would answer.

Empowering messaging to parents: On the inpatient unit, the parents were told that the most important treatment would be measures to comfort the infant, and that these measures should be performed by the mother or father (or other family member). Parents were told that they needed to be present at the hospital as much as possible. Nurses and doctors focused on supporting and coaching parents.

Novel approach to assessment: Instead of using FNASS scores for babies on the inpatient unit (these scores were still used in the WBN and the NICU), the researchers developed their own assessment focused on three parameters: the infant’s ability to eat, to sleep and to be consoled. If the infant couldn’t breastfeed or take at least one ounce from a bottle, or sleep for more than an hour, and took 10 minutes or more to be consoled when crying, nonpharmacologic interventions were maximized. If these didn’t work, morphine was either started or increased.

Morphine as needed: Instead of using rapid morphine weans on a schedule, the researchers modified their approach to give morphine as needed. “We noticed that signs of withdrawal were not always consistent throughout the day,” the researchers wrote. “In addition, sometimes we were unable to provide optimal nonpharmacologic care, such as when no parent, family member, or volunteer could be present.” If the maximal nonpharmacologic interventions were not effective, the infant would get one dose of morphine. If the infant was sleeping well, eating well and consolable within 10 minutes, additional doses of morphine were not administered.

The level IV NICU housed infants with NAS in rooms with as many as 12 infants. There was no ability for parents to room-in, and the environment was not low-stimulation. “We discontinued the practice of directly admitting infants at risk for NAS to the NICU after birth in an effort to keep the mother-infant dyad intact,” the researchers wrote. Instead, these infants were taken to the WBN, where FNASS scores were measured, and if the score was 8 or more, the babies were transferred to the inpatient unit, where the mothers could room-in and nonpharmacologic measures were initiated as soon as possible for all opioid-exposed infants, whether they had withdrawal signs or not.


There were 287 infants who met inclusion criteria between January 2008 and June 2016. The ALOS decreased from 22.4 days during the baseline period to 5.9 days in the post-implementation period. In 2010, the nonpharmacologic interventions were standardized; in December 2011, the babies started being transferred directly to the inpatient unit so they could room-in; in January 2014, the novel assessment approach on the inpatient unit began; in June 2014, implementation of prenatal counseling and rapid morphine weaning began; and in June 2015, rapid morphine weaning was replaced by as-needed morphine dosing and empowering messaging to parents began. Overall, the proportion of infants treated with morphine decreased from 98 percent to 14 percent, and the average cost of hospitalization decreased from $44,824 to $10,289.

For those infants transferred from the WBN to the NICU, only 6 percent (2 of 35) received morphine. The proportion of infants who took most of their feeding from breast milk increased from 20 percent to 45 percent. The proportion of infants admitted directly to the NICU decreased from 100 percent to 20 percent. No patient admitted to the inpatient unit required transfer to an ICU. There were no seizures and no readmissions within 30 days.


The changes in treatment of NAS — to less medical and more parental involvement — went far beyond the researchers’ goal of a 50 percent reduction in ALOS. The eight plan-do-study-act cycles led to an improvement in ALOS, well below that reported in any other published studies, and “we are confident that our interventions directly resulted in the changes observed,” they wrote.

“One of our study’s strengths was the inclusion of all methadone-exposed infants, which allowed us to fully measure the impact of our interventions,” they wrote.

Many studies define NAS as receiving pharmacologic treatment — in other words, only babies who received morphine count as having NAS. But that definition makes it impossible to draw conclusions about the effectiveness of nonpharmacologic interventions, the researchers note. “The use of medication to treat clinical signs should not be the sole factor used to define the syndrome,” they wrote. “Although we applied our interventions to all opioid-exposed infants, we focused our evaluation on the subset of opioid-exposed infants most likely to develop withdrawal, regardless of the eventual treatment received.”

Because methadone is a long-acting opioid, infants exposed to it are more likely to have signs of withdrawal than those exposed to short-acting opioids or buprenorphine, the researchers wrote. “By initiating intensive nonpharmacologic interventions for all methadone-exposed infants from the time of birth and before the presentation of clinical signs of withdrawal, we were able to intervene earlier and to prepare parents for their critical role in treatment,” they wrote. “We believe this strategy contributed greatly to our success.”

The researchers also said there has never been validation of starting or changing pharmacologic treatment for NAS based on FNASS scores. In addition, it’s impossible to obtain an FNASS score without disturbing and unswaddling the baby, which increases the likelihood of high scores in terms of tremors, tone and cry. “Our approach encouraged providers to focus on a small number of clinically relevant factors to assess the need for treatment with morphine,” they wrote. “Ideally, all infants should feed well, sleep well, and be easily consoled. We determined that if infants with NAS met these goals, then treatment was successful irrespective of the FNASS score.”

When less is more

A decade ago, all infants with NAS were admitted straight to the NICU, where rooming-in was not permitted and the only nonpharmacologic intervention was swaddling. In this setting, 98 percent of the babies exposed to methadone required morphine. By changing the milieu, the intervention changed an entire system, to one in which parents were not only allowed to visit their baby but encouraged to be the most important part of their baby’s treatment. “This approach employed the power of the maternal-infant bond to treat NAS,” the researchers wrote.

By changing the paradigm, the researchers reduced the use of morphine, the ALOS and costs.

The study, “An Initiative to Improve the Quality of Care of Infants with Neonatal Abstinence Syndrome,” is in the current issue of Pediatrics and was funded by the National Institutes of Health, and the researchers reported they had no conflicts of interest to disclose.