Symptom-Based Dosing for Neonatal Opioid Withdrawal

Importance: Infants with neonatal opioid withdrawal syndrome (NOWS) who receive pharmacologic treatment are traditionally treated with a scheduled opioid taper. An alternate approach, symptom-based dosing, may better align treatment with withdrawal severity. Objective: To compare time from birth to medical readiness for discharge for infants with moderate to severe withdrawal treated with either a symptom-based dosing or scheduled opioid taper approach. Design, Setting, and Participants: In this cluster, crossover randomized clinical trial with run-in period, 23 US hospitals cared for infants using the Eat, Sleep, Console approach (ESC) or Finnegan-based care (a comprehensive scoring system to quantify severity of symptoms; 15 ESC and 8 Finnegan hospitals) and their preferred primary opioid. Opioid dosing was guided by study-approved, site-specific algorithms. Infants with NOWS with a gestational age at birth of at least 36 weeks and at risk for pharmacologic treatment were enrolled between March 25, 2024, and April 9, 2025, with the last 3-month assessment on July 15, 2025. Sample size analyses were conducted between August 1, 2024, and September 23, 2024. Intervention: Sites were randomized to 1 of 2 sequences: (1) symptom-based dosing followed by scheduled opioid taper or (2) scheduled opioid taper followed by symptom-based dosing. Main Outcome and Measure: Time from birth to medical readiness for discharge. Results: Of the 626 enrolled infants (mean [SD] gestational age, 38 [1] weeks; 49% male), 383 were cared for with ESC (primary outcome cohort). The mean time to medical readiness for discharge was significantly shorter in the symptom-based dosing group compared with the scheduled opioid taper group (9.18 vs 11.61 days; adjusted mean ratio [aMR], 0.79 [95% CI, 0.65-0.96]). There was no difference in the risk for initiation of pharmacologic treatment (0.4 vs 0.41; adjusted risk ratio, 0.99 [95% CI, 0.77-1.27]) or length of stay (10.91 vs 12.09 days; aMR, 0.9 [95% CI, 0.72-1.13]) between groups. For infants in the symptom-based group, 35% (95% CI, 25%-45%) required scheduled opioid dosing due to withdrawal severity that was not controlled with intermittent dosing. In the Finnegan cohort (n = 243; planned secondary outcome), there were no significant differences in time to medical readiness for discharge (15.99 vs 17.56 days; aMR, 0.91 [95% CI, 0.72-1.15]) or length of stay (17.38 vs 19.39 days; aMR, 0.9 [95% CI, 0.69-1.16]). The inpatient composite safety outcome occurred rarely (in the ESC cohort, 3 of 188 in the symptom-based dosing vs 2 of 195 in the scheduled opioid taper groups). Conclusions and Relevance: Symptom-based dosing decreased time to medical readiness for discharge compared with a scheduled opioid taper approach among infants cared for with ESC. Trial Registration: ClinicalTrials.gov Identifier: NCT05980260.

Authors

Institutions

Publication Details

Journal
JAMA
Published
2026-04-25
DOI
https://doi.org/10.1001/jama.2026.5782
Citations
1
Primary Topic
Prenatal Substance Exposure Effects
Type
article
Field-Weighted Citation Impact
29.09
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Symptom-Based Dosing for Neonatal Opioid Withdrawal

Savannah Moore, Susan Adeniyi-Jones, Bhanu Muniyappa, Scott A. McDonald et al.
1 citations
JAMA
Prenatal Substance Exposure Effects
29.09
article

Symptom-Based Dosing for Neonatal Opioid Withdrawal

Savannah Moore, Susan Adeniyi-Jones, Bhanu Muniyappa, Scott A. McDonald, Cathy Grisby, Hannah Rakow, Beth McKinney-Whitlock, Patricia K. Williams, Traci Beiersdorfer, Lori A. Devlin, A. Keyes, Scott L. Wexelblatt, Stephanie L. Merhar, Carla King, Kelley Kovatis, Amy Mackley, Betty Oberle, Rachel Benz, Denise C. Babineau, Waldemar A. Carlo, Karen Herzing, Richard Hall, Walter K. Kraft, Sara B. DeMauro, Lawrence Leeman, Namasivayam Ambalavanan, Gregory M. Sokol, Angela Pallotto, Mary Connolly, Kristina Foster, Krishna Dummula, Amanda Wilburn, Vallon Williams, Natalie Goodman, Thitinart Sithisarn, Jennifer M. McAllister, Crystal D. Hill, Stephanie Wilson Archer, Jennifer A. Tioseco, Samuel J. Gentle, D Leblond, Lisa Tully, Sharon Owen, Lillian Trochinski, Ryan Smith, Anna E. Thomas, Sucheta Telang, E. Leeon Rhodes, Carrie Hobbs, Allyson Cheathem, Jenny Auman, Brenda Poindexter, Margaret Crawford, Myriam Peralta-Carcelen, Anna Mazur, Ann Anderson-Berry, Emily J. Murray, David Russell, Molly Hemmerle, Lynette Johnson, Scott D. Duncan, Courtenay Fulmor, Emily Smith, Allison Dymacek, Leslie W. Young, Erin Bohon, Rachel Welch-Miles, Loren Nallu, Karen Puopolo, James Pickett, Crystal Bass, Susan DeGraaff, Brittany Thomas, Audrey Miller, Elizabeth Hendricks, Madison Jessie, Abhik Das, Jonathan M. Davis, Sarah Morris, Mina Hanna, Eugene Turner, Jessica Mendoza, Shannon Barnes, Melette Pearson, David Paul, Megan Lennon Kundrat, Henrietta Bada, Aprill Shockley, Allison Scott, Sandra Turner, Scott A. Lorch, Betsy Tudor, Lisa Pullaro, Ward Rice, Crystal Wilson, Cynthia Reid, Tanner Wright, Augusto F. Schmidt, Jennifer Chambers, Jennifer Nason
article en
1 citations

Abstract

Importance: Infants with neonatal opioid withdrawal syndrome (NOWS) who receive pharmacologic treatment are traditionally treated with a scheduled opioid taper. An alternate approach, symptom-based dosing, may better align treatment with withdrawal severity. Objective: To compare time from birth to medical readiness for discharge for infants with moderate to severe withdrawal treated with either a symptom-based dosing or scheduled opioid taper approach. Design, Setting, and Participants: In this cluster, crossover randomized clinical trial with run-in period, 23 US hospitals cared for infants using the Eat, Sleep, Console approach (ESC) or Finnegan-based care (a comprehensive scoring system to quantify severity of symptoms; 15 ESC and 8 Finnegan hospitals) and their preferred primary opioid. Opioid dosing was guided by study-approved, site-specific algorithms. Infants with NOWS with a gestational age at birth of at least 36 weeks and at risk for pharmacologic treatment were enrolled between March 25, 2024, and April 9, 2025, with the last 3-month assessment on July 15, 2025. Sample size analyses were conducted between August 1, 2024, and September 23, 2024. Intervention: Sites were randomized to 1 of 2 sequences: (1) symptom-based dosing followed by scheduled opioid taper or (2) scheduled opioid taper followed by symptom-based dosing. Main Outcome and Measure: Time from birth to medical readiness for discharge. Results: Of the 626 enrolled infants (mean [SD] gestational age, 38 [1] weeks; 49% male), 383 were cared for with ESC (primary outcome cohort). The mean time to medical readiness for discharge was significantly shorter in the symptom-based dosing group compared with the scheduled opioid taper group (9.18 vs 11.61 days; adjusted mean ratio [aMR], 0.79 [95% CI, 0.65-0.96]). There was no difference in the risk for initiation of pharmacologic treatment (0.4 vs 0.41; adjusted risk ratio, 0.99 [95% CI, 0.77-1.27]) or length of stay (10.91 vs 12.09 days; aMR, 0.9 [95% CI, 0.72-1.13]) between groups. For infants in the symptom-based group, 35% (95% CI, 25%-45%) required scheduled opioid dosing due to withdrawal severity that was not controlled with intermittent dosing. In the Finnegan cohort (n = 243; planned secondary outcome), there were no significant differences in time to medical readiness for discharge (15.99 vs 17.56 days; aMR, 0.91 [95% CI, 0.72-1.15]) or length of stay (17.38 vs 19.39 days; aMR, 0.9 [95% CI, 0.69-1.16]). The inpatient composite safety outcome occurred rarely (in the ESC cohort, 3 of 188 in the symptom-based dosing vs 2 of 195 in the scheduled opioid taper groups). Conclusions and Relevance: Symptom-based dosing decreased time to medical readiness for discharge compared with a scheduled opioid taper approach among infants cared for with ESC. Trial Registration: ClinicalTrials.gov Identifier: NCT05980260.

JAMA
University of Vermont (US), Christiana Care Health System (US), Cincinnati Children's Hospital Medical Center (US), Tufts Medical Center (US), Good Samaritan Hospital (US), Children's Mercy Hospital (US), Children's Hospital of Philadelphia (US), University of Louisville (US), Thomas Jefferson University (US), Emory University (US), University of New Mexico (US), RTI International (US), University of Utah (US), University of South Florida (US), St. Elizabeth Healthcare (US), University of Alabama at Birmingham (US), Children's Hospital of Oklahoma (US), Roshydromet (RU), RTI Health Solutions (US), Golisano Children's Hospital (US), Mercy Hospital (US), University of Kansas Medical Center (US), Perinatal Institute (GB), Norton Women's and Children's Hospital (US), Norton Hospital (US), University of Louisville Hospital (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), AtlantiCare (US), Indiana University School of Medicine, University of Oklahoma Health Sciences Center (US), University of Rochester (US), Indiana University – Purdue University Indianapolis (US), University of Nebraska Medical Center (US), University of Pennsylvania (US), University of Arkansas for Medical Sciences (US)
Good health and well-being
Openalex Percentile: Top 0%
Prenatal Substance Exposure Effects
29.09
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.