Neonatal Abstinence Signs during Treatment: Trajectory, Resurgence and Heterogeneity

Jennifer S. Miller, Henrietta S. Bada, Philip M. Westgate, Thitinart Sithisarn, Markos Leggas

Research output: Contribution to journalArticlepeer-review


Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized estimating equations with a within-subject exchangeable correlation structure. The median LOT was 12.86 days. The prevalence of withdrawal signs decreased from day one to day three of treatment. However, certain central nervous system (CNS) and gastrointestinal (GI) signs showed sporadic increases in prevalence notable around two weeks of treatment, accounting for increases in Finnegan scores that guided pharmacotherapy. We question whether the resurgence of signs with a prolonged LOT is mainly a consequence of opioid tolerance or withdrawal. Monitoring CNS and GI signs throughout treatment is crucial. Future studies directed to better understand this clinical phenomenon may lead to the refining of NAS pharmacotherapy and perhaps the discovery of treatment alternatives.

Original languageEnglish
Article number203
Issue number2
StatePublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.


  • CNS/GI withdrawal signs trajectory
  • Finnegan neonatal abstinence scoring tool (FNAST)
  • gut–brain axis
  • length of treatment (LOT)
  • neonatal abstinence syndrome (NAS)
  • neonatal opioid withdrawal syndrome (NOWS)
  • withdrawal sign resurgence

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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