Neonatal opioid withdrawal syndrome is a growing problem in the United States, with at least one newborn diagnosed every 18 minutes due to in-utero opioid exposure. The clinical signs of this syndrome necessitate close monitoring and focused care, which prolongs hospitalizations. Unfortunately, there is no standard approach to care, resulting in highly varied treatment options and a lack of evidence-based alternatives. For nearly 50 years, care has relied on subjective, observer-rated scales that overestimate the need for pharmacologic treatment. In 2014, the Eat, Sleep, Console approach was proposed as an alternative, focusing on function-based assessment and nonpharmacologic interventions.
Although this approach is increasingly used, concerns about its efficacy, safety, and generalizability across diverse populations and varied care settings have arisen. To address these concerns, the Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) collaborative conducted a randomized, controlled trial called Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal (ESC-NOW) to evaluate the safety, efficacy, and generalizability of the Eat, Sleep, Console approach compared with usual care using the Finnegan tool.
A new study published in The New England Journal of Medicine has found that using the Eat, Sleep, Console care approach can significantly reduce the time until infants with opioid withdrawal are medically ready for hospital discharge without any short-term adverse safety outcomes.
The multicenter, stepped-wedge, cluster-randomized, controlled trial was conducted across diverse sites and populations, including those not previously represented in the literature. The trial found that the approach decreased the time until medical readiness for discharge by 6.7 days, compared to usual care. It also decreased the proportion of infants who received pharmacologic treatment by 32.5 percentage points.
To minimize potential bias in favor of the Eat, Sleep, Console approach that could arise from discharging infants too early, the trial’s primary outcome measure was the length of time until infants were medically ready for discharge. This allowed for a more comprehensive assessment of the infants’ health status and ensured that the approach was not associated with any undue risk of premature discharge.
The trial used standards endorsed by the American Academy of Pediatrics to guide the definition of medical readiness for discharge. Post-hoc analysis using modifications to the original definition based on the 2020 update to the standards produced similar results to the primary analysis. Lengths of stay for both groups were consistent with those historically reported and in keeping with outcomes from quality-improvement initiatives that have assessed the Eat, Sleep, Console approach.
Infants in the Eat, Sleep, Console group were treated with opioids less often than those receiving usual care. This supports the premise that the new approach facilitates a more judicious medication use for these infants. The judicious use of pharmacologic treatment is essential to improving short-term outcomes for infants with opioid withdrawal.
Although pharmacologic treatment has been shown to be effective, there is still uncertainty about the optimal timing for initiating treatment. Therefore, continued monitoring of long-term neurodevelopmental and behavioral outcomes, as well as the well-being of both the infants and their families, will be crucial in shaping clinical practice in this area. It is important to include a subgroup of trial patients in these assessments to ensure that the most accurate and informative data are obtained.
The trial found no material differences between groups for specified safety outcomes through 3 months of age. This indicates that the Eat, Sleep, Console approach appears as safe as usual care for infants with opioid withdrawal through early infancy. Short-term adverse safety events were rare throughout the trial.
Limitations of the trial include the unmasked nature of the stepped-wedge design and its vulnerability to treatment contamination and temporal trends. The potential for contamination was addressed by limiting access to intervention-specific materials until sites neared their transition period. The chosen primary outcome limited the potential effect of earlier discharges of newborns. Post discharge safety outcomes were limited to the first three months of age, and longer-term follow-up is planned to reassess critical safety outcomes for all enrolled infants at two years of age.
The observed treatment effect for this trial, which was more significant than hypothesized, supports the generalizability of the Eat, Sleep, Console approach across various sites and varied populations. Additional research is needed to investigate potential factors that may contribute to differences in treatment outcomes, including variations in patient populations across different sites, the geographic location where care is provided, and the use of non-pharmacological interventions as part of standard care.
Such studies would provide valuable insights and help refine the use of this treatment approach. In conclusion, the multicenter, randomized, controlled trial provides evidence that the Eat, Sleep, Console approach can substantially decrease the time until infants with opioid withdrawal are medically ready for hospital discharge without any short-term adverse safety outcomes.
