Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal
Authors: Devlin Lori A. , Hu Zhuopei , Merhar Stephanie L. , Ounpraseuth Songthip T. , Simon Alan E. , Lee Jeannette Y. , Das Abhik , Crawford Margaret M. , Greenberg Rachel G. , Smith P. Brian , Higgins Rosemary D. , Walsh Michele C. , Rice Ward , Paul David A. , Maxwell Jessie R. , Fung Camille M. , Wright Tanner , Ross Julie , McAllister Jennifer M. , Crowley Moira , Shaikh Sophie K. , Christ Lori , Brown Jaime , Riccio Julie , Wong Ramsey Kara , Braswell Erica F. , Tucker Lauren , McAlmon Karen , Dummula Krishna , Weiner Julie , White Jessica R. , Newman Sarah , Snowden Jessica N. , Young Leslie W. ,   Eunice Kennedy Shriver NICHD Neonatal Research Network and NIH Environmental Influences on Child Health Outcomes (ECHO) Program Institutional Development Award States Pediatric Clinical Trials Network, Hubberd De Ann , Edwards Kathy , Whalen Bonny L. , MacMillan Kate , Pahl Adrienne , Sheehan Desselle Farrah , White Katie , Hibbs Anna Marie , Clarke Leslie , Serio Kathy , Kertesz Maria , Rodriguez Ashley , Driscoll Sarah , Hammond Kim , Hines Deborah , Kish Patricia , Schmidt Taylor , Stepp Jennifer , Jackson Jodi , Scott Allie , Brown Rochelle , Smith Kari , Rieper My , Miner Carrie , Ray Lynne , Kowel Karen , Reynolds Victoria , Castellone Diana , Mackley Amy , Schibler Kurt , Beiersdorfer Traci , Grisby Cathy , Kirker Kristin , McKeown Katherine , Loudermilk M. Katherine , Carnohan Amy , Froese Patti , Haddix April , Summe Virginia , Chlon Clara , Kunk Rita , Hamilton Jen , Moore Sadie , Ziegelmeyer Angela , Rolfes Lucy , Schomaker Erica , Strike Holly , Harvey Sharon , Richards Paula , Simon Ashley , Russell David , Gleason Christine A. , Allen Marilee C. , Boyle Robert J. , Clemons Traci , D’Alton Mary E. , Steinhorn Robin , Weiner Steven J. , Blaisdell Carol J. , Wilson Archer Stephanie , Amiotte Annette , Santos Moara , Taosaka Jill , Neal Charles , Atz Andrew M. , Summer Andrea , Amaya Michelle , Freeman Mary , Johnson Madison , Sarraf Layla Al , Ros-Demarize Rosemary , Sánchez Pablo J. , Slaughter Jonathan L. , Benninger Kristen , Luzader Patricia , Marzec Laura , DeSantis Brittany , Small Kristi , Newton Julia , Purnell Jessica , Reedy Rachel , Hanlon Cory , Naik Tanvi , Knox Jordan , Tallikar Aishwarya , Cobe Chelsea , Resetar Megan , McCool Jacqueline , Frailey Erin , Jones Stephanie , Williams Stacy , Staton Taise , Palmer Jacqueline N. , Erner Jana L. , Kovalcik Jason B. , Keels Erin L. , McCarty Teri , Harris Katherine , DeSpain Meagan , Boyd Jackie , Watson Sara , Sullivan Jan , Walsh Timothy , Anderson Brianna , Hahn Devon , Madden Christi , Nascimbeni Anne , Wilson Shannon , Gibson Theresa , Karlin John , Bann Carla M. , O’Donnell Auman Jeanette , Turner Eugene , Smith Emily , Bradley Lauren , Trochinski Lillian , Gabrio Jenna , Leblond David , Pickett James , Newman Jamie E. , Zaterka-Baxter Kristin M. , Baack Michelle L. , Hogden Laurie A. , Elenkiwich Chelsey , Henning Megan M. , Van Muyden Sarah , Martino Anna-Lisa , Lutz Allison , Nelson Jeralyn , Schumacher Bette , Brodkorb Aimee , Pritchett Deborah , Ford Kristen , Howard Darla , Orland Ryan , Diles Monique , Shuttleworth Kay L. , Hubberd DeAnn E. , Edwards Kathy D. , Lloyd Sherry L. , Banks-Johnson Catrice , Robinson Patrina , Griffith Melissa , Slaughter Amie , Kilkenny Teresa , Foster Kristina , Cross Morgan , Gier Jessica , Roberts Natalie , Wadman Jessica , Cathey Kathy , Todd Jenna , Fratesi Emily , Malloch Lacy , Alur Radha , Majure Joseph Marc , Walker Courtney , Powers Catherine , Annett Robert D. , Wellman Rachel , Miller Kerry , Anderson-Berry Ann , Raissy Hengameh , Kong Alberta , McCalmont Kate , Sundquist Beauman Sandra , Sanders Sarah , Eichenwald Eric C. , Mancini Toni , Ziolkowski Kristina , Dhawan Megan , Gambacorta Mary Kay , Pulsifer Allie , Brant Marisa , Schumacher Aida , Gocial Sydney , Azuma Kristen , Quigley Elizabeth , Zachritz Whitney , Pastore Nicole , Barber Jessica , McDowell Abby , Ferri Alissa , Parga-Belinkie Joanna , Guillet Ronnie , Jensen Rosemary L. , Kent Alison , Scorsone Ann Marie , Lakshminrusimha Satyan , Hartley-McAndrews Michelle E. , Li Emily , Donato Jennifer , McKee Kimberly G. , D’Angio Carl , Jones Rachel , Terrano Dacia , Solpietro Stephanie , Brei Lisa , Krokovich Lisa , Hart Sema , Pastore John , Kern Ashley , Mars Margaret , Volker Patricia , Mioneo Brady Annette , Voelker Kelsey , Horn Emily , Moreland Melissa , Kneusel Marcia , Balakrishnan Maya , Childres Jillian , Hanniman Melissa , White Rebecca , Ohls Robin K. , Baserga Mariana , Muniyappa Bhanu , Shakib Julie , Rau Carrie A. , Baker Shawna , Coleman Kathie , McGrath Kandace M. , Petersen Brandy , Waldvogel Jael , Bracken Monika , Ferrin Meredith , DeSantis Holly , Perkins Traci , Loertscher Manndi C. , McAlmon Karen , Goldstein Justin , Angelidou Asimenia , Donahue Nancy 
Published: April 2024

Importance

The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown.

Objective

To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool.

Design, Setting, and Participants

This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks’ gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024.

Exposure

Opioid treatment for NOWS and the ESC care approach.

Main Outcomes and Measures

For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics.

Results

In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P &amp;lt; .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P &amp;lt; .001).

Conclusion and Relevance

When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later.

Trial Registration

ClinicalTrials.gov Identifier: NCT04057820