Neonatal Abstinence Syndrome: Advances in Diagnosis and Treatment

JAMA. 2018 Apr 3;319(13):1362-1374. doi: 10.1001/jama.2018.2640.


Importance: Neonatal abstinence syndrome, which occurs as a result of in utero opioid exposure, affects between 6.0 and 20 newborns per 1000 live US births. There is substantial variability in how neonatal abstinence syndrome is diagnosed and managed.

Objective: To summarize key studies examining the diagnosis and management (both pharmacologic and nonpharmacologic) of neonatal abstinence syndrome published during the past 10 years.

Evidence review: PubMed, Web of Science, and CINAHL were searched for articles published between July 1, 2007, and December 31, 2017. Abstracts were screened and included in the review if they pertained to neonatal abstinence syndrome diagnosis or management and were judged by the authors to be clinical trials, cohort studies, or case series.

Findings: A total of 53 articles were included in the review, including 9 randomized clinical trials, 35 cohort studies, 1 cross-sectional study, and 8 case series-representing a total of 11 905 unique opioid-exposed mother-infant dyads. Thirteen studies were identified that evaluated established or novel neonatal abstinence syndrome assessment methods, such as brief neonatal abstinence syndrome assessment scales or novel objective physiologic measures to predict withdrawal. None of the new techniques that measure infant physiologic parameters are routinely used in clinical practice. The most substantial number of studies of neonatal abstinence syndrome management pertain to nonpharmacologic care-specifically, interventions that promote breastfeeding or encourage parents to room-in with their newborns. Although these nonpharmacologic interventions appear to decrease the need for pharmacologic treatment and result in shorter hospitalizations, the interventions are heterogeneous and there are no high-quality clinical trials to support them. Regarding pharmacologic interventions, only 5 randomized clinical trials with prespecified sample size calculations (4 infant, 1 maternal treatment) have been published. Each of these trials was small (from 26 to 131 participants) and tested different therapies, limiting the extent to which results can be aggregated. There is insufficient evidence to support an association between any diagnostic or treatment approach and differential neurodevelopmental outcomes among infants with neonatal abstinence syndrome.

Conclusions and relevance: Evidence pertaining to the optimal diagnosis and treatment strategies for neonatal abstinence syndrome is based on small or low-quality studies that focus on intermediate outcomes, such as need for pharmacologic treatment or length of hospital stay. Clinical trials are needed to evaluate health and neurodevelopmental outcomes associated with objective diagnostic approaches as well as pharmacologic and nonpharmacologic treatment modalities.

Publication types

  • Review

MeSH terms

  • Acupuncture Therapy
  • Analgesics / therapeutic use*
  • Breast Feeding*
  • Buprenorphine / therapeutic use
  • Clonidine / therapeutic use
  • Female
  • Humans
  • Infant, Newborn
  • Methadone / therapeutic use
  • Morphine / therapeutic use
  • Mothers
  • Neonatal Abstinence Syndrome / diagnosis*
  • Neonatal Abstinence Syndrome / drug therapy
  • Neonatal Abstinence Syndrome / therapy*
  • Opiate Substitution Treatment*
  • Rooming-in Care*


  • Analgesics
  • Buprenorphine
  • Morphine
  • Clonidine
  • Methadone