Trial: Functional Scoring a Better Guide to Neonatal Opioid Withdrawal Tx

A newer function-based approach to treating neonatal opioid withdrawal syndrome safely readied babies to go home sooner, the ACT NOW randomized trial showed.

With the Eat, Sleep, Console care approach, time from birth to medical readiness for hospital discharge by American Academy of Pediatrics-endorsed standards was nearly a week sooner than when treating guided by the traditional, subjective Finnegan Neonatal Abstinence Scoring Tool (8.2 vs 14.9 days, RR 0.55, 95% CI 0.46-0.65, P<0.001).

The popular new approach also decreased the proportion of infants who received pharmacologic (often opioid) treatment by 32.5 percentage points, researchers led by Leslie W. Young, MD, of the University of Vermont in Burlington, reported in the New England Journal of Medicine.

Adverse events (a composite of in-hospital safety, unscheduled healthcare visits, and nonaccidental trauma or death) were similar between groups through the available follow-up to 3 months of age, although Young’s group acknowledged that the planned reassessment at age 2 years will be “critical to further inform the safety of this approach.”

The Eat, Sleep, Console Care Tool defines withdrawal severity based on an infant’s ability to eat, sleep, and be consoled. The approach calls for nonpharmacologic interventions – such as a low-stimulation environment, skin-to-skin contact, clustered care, and breast-feeding — as the first line of treatment.

It’s been increasingly adopted both in the U.S. and internationally based on favorable evaluation by several statewide and regional quality-improvement initiatives.

However, “rapid spread of this approach without strong evidence to support its efficacy, safety, or generalizability across diverse populations and varied care settings has caused concerns,” particularly for pharmacologic undertreatment and for premature discharge, leading to increased risk for readmission, nonaccidental trauma, and death, Young’s group wrote.

The trial was conducted at 26 U.S. hospitals, which were randomly assigned by cluster to when they would transition from usual care with the Finnegan tool to the Eat, Sleep, Console approach. To minimize potential for contamination of treatment effect, materials and training on use of the newer approach wasn’t begun until a 3-month transition period before the switch. Infants weren’t enrolled during the transition period. The centers were geographically diverse and included both academic and community facilities to ensure broad generalizability.

The main intention-to-treat analysis included 837 infants who met the trial definition for medical readiness for discharge, out of the 1,305 infants enrolled with neonatal opioid withdrawal syndrome at birth after at least 36 weeks’ gestation.

“We chose the time until medical readiness for discharge as the primary outcome because issues unrelated to opioid withdrawal often prolong hospital stays for these infants,” Young’s group wrote. “This choice also guarded against possible bias in favor of the Eat, Sleep, Console approach that might result from the premature discharge of infants, a concern that has previously been raised about this approach.”

Actual discharge followed usual site practices, independent of the trial criteria for medical readiness for discharge. Those criteria in the protocol were being at least 96 hours post delivery, at least 48 hours without receiving an opioid, at least 24 hours with no respiratory support, and at least 24 hours from initiation of maximum caloric density on 100% oral feeding. Hospital stays averaged 7.8 days after the transition in approach, compared with 14.0 days with usual care (RR 0.56, 95% CI 0.49-0.64).

Among the other secondary endpoints, the Eat, Sleep, and Console approach significantly reduced opioid treatment by a relative 62% (rate 19.5% vs 52.0%). For safety, the composite endpoint through 3 months of age was similar compared with usual care (16.1% and 15.8%, respectively, RR 1.02, 95% CI 0.71-1.47).

The researchers noted that the patient population was largely representative of U.S. opioid withdrawal neonate cases, although slightly overrepresenting non-Hispanic Black and Hispanic infants.

They acknowledged limitations including the unmasked stepped-wedge design vulnerable to temporal trends, such as those brought on by the COVID-19 pandemic during which the trial was conducted (September 2020-March 2022). “The chosen primary outcome limited the potential effect of earlier discharges of newborns,” the researchers noted. “We speculate that visitation restrictions and nurse shortages would make implementation and use of the Eat, Sleep, Console approach more challenging and that these changes would attenuate the treatment effect.”

They also noted that just when pharmacologic treatment is indicated in infants with opioid withdrawal remains unclear. “Results from the ongoing assessment of longer-term neurodevelopmental and behavioral outcomes and assessment of family and infant well-being in a subgroup of trial patients will be critical to informing this practice.”

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