An Improved Treatment Model for Neonatal Opioid Withdrawal Syndrome

Study comparing two models of care shows benefits of symptom-triggered dosing over a fixed medication schedule.
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The increased use of unprescribed and prescribed opioids in the accelerating opioid crisis has not spared pregnant women, and infants exposed to opioids in utero are often the unintended target of substance use disorder. Over the past decade, researchers have seen a five-fold increase in the rate of neonatal opioid withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), in which the baby experiences uncomfortable withdrawal symptoms two to three days after birth.

Approximately 50–80% of these opioid-exposed infants require medication to manage their symptoms of withdrawal, including irritability, trouble eating and sleeping, diarrhea, muscle rigidity, and difficulty soothing. Currently, the standard of treatment for these symptoms involves methadone, morphine, or buprenorphine given on a fixed tapering schedule. It also involves an average of 23 days in the hospital and approximately $93,000 in hospital bills.

For new parents with substance use disorder, these numbers are hardly manageable, and the impact on the child isn’t negligible, either. Recently, researchers explored whether a novel symptom-triggered approach for administering medication could be a more effective intervention for these infants and a step in reducing unnecessary medication exposure.

Symptom-triggered dosing: A novel approach

The findings of this research, which comes from Boston Medical Center and was published in Hospital Pediatrics, indicate that treating NOWS symptoms when and if they arise rather than on a standard schedule could be a more effective intervention with several other benefits, including reducing unnecessary medication exposure for these infants.

Currently, the standard of treatment for NOWS symptoms involves an average of 23 days in the hospital and approximately $93,000 in hospital bills.

During postpartum hospitalization for NOWS, all infants with the condition were assessed every four hours on their ability to eat, sleep, and be consoled. Clinicians used nonpharmacologic care interventions, like parental presence at the bedside, breastfeeding, and rooming in, as first-line treatment for NOWS symptoms. Research has shown this type of first-line care reduces costs, hospital length of stay, and the need for medication.

If an infant had difficulties after using the nonpharmacologic treatments, then the healthcare team determined if medication was the appropriate next step. Researchers in this study investigated two treatment approaches for infants who required medication for NOWS: a fixed dosing and taper schedule and a symptom-triggered dosing approach.

Between June 2016 and November 2017, methadone was dosed every eight hours with the traditional slow taper. Between December 2017 and May 2018, the researchers implemented the novel symptom-triggered approach, which was developed by clinician researchers at BMC as a way to reduce the risk of creating a dependence on the opioid medication by focusing on keeping the infants comfortable and treating symptoms only as needed.  

Promising results

Elisha Wachman, MD, a neonatologist at BMC and the study’s corresponding author, explains that her team found several benefits to an as-needed model for dosing.

“This novel approach prioritizes the nonpharmacologic care approach for infants experiencing withdrawal symptoms and decreases the risk for unintended dependence that frequently occurs when infants are placed on prolonged methadone or morphine tapers,” she says.


Infants who were treated using the symptom-triggered approach had a shorter median length of stay by more than a third, which may be explained in part by the 5.6 fewer days of methadone treatment babies needed on the symptom-triggered approach compared to the fixed-medication schedule group. The percentage of infants who were successfully treated using the symptom-triggered methods reached 100 percent by the end of the study period, with no adverse events.

Due to its success and the body of research that advises against prolonged exposure to methadone for infants, the researchers propose that this symptom-triggered approach become a first line of treatment after nonpharmacologic approaches fail, with the fixed methadone dosing and taper approach becoming an option for more difficult cases.