Variation in treatment of neonatal abstinence syndrome in US children's hospitals, 2004-2011

J Perinatol. 2014 Nov;34(11):867-72. doi: 10.1038/jp.2014.114. Epub 2014 Jun 12.


Objective: Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome experienced by opioid-exposed infants. There is no standard treatment for NAS and surveys suggest wide variation in pharmacotherapy for NAS. Our objective was to determine whether different pharmacotherapies for NAS are associated with differences in outcomes and to determine whether pharmacotherapy and outcome vary by hospital.

Study design: We used the Pediatric Health Information System Database from 2004 to 2011 to identify a cohort of infants with NAS requiring pharmacotherapy. Mixed effects hierarchical negative binomial models evaluated the association between pharmacotherapy and hospital with length of stay (LOS), length of treatment (LOT) and hospital charges, after adjusting for socioeconomic variables and comorbid clinical conditions.

Result: Our cohort included 1424 infants with NAS from 14 children's hospitals. Among hospitals in our sample, six used morphine, six used methadone and two used phenobarbital as primary initial treatment for NAS. In multivariate analysis, when compared with NAS patients initially treated with morphine, infants treated with methadone had shorter LOT (incidence rate ratio (IRR) = 0.55; P < 0.0001) and LOS (IRR = 0.60; P < 0.0001). Phenobarbital as a second-line agent was associated with increased LOT (IRR = 2.09; P<0.0001), LOS (IRR = 1.78; P < 0.0001) and higher hospital charges (IRR = 1.84; P < 0.0001). After controlling for case-mix, hospitals varied in LOT, LOS and hospital charges.

Conclusion: We found variation in hospital in treatment for NAS among major US children's hospitals. In analyses controlling for possible confounders, methadone as initial treatment was associated with reduced LOT and hospital stay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comorbidity
  • Female
  • Hospital Charges
  • Hospitals, Pediatric
  • Humans
  • Infant, Newborn
  • Length of Stay
  • Male
  • Multivariate Analysis
  • Neonatal Abstinence Syndrome / drug therapy*
  • Neonatal Abstinence Syndrome / epidemiology
  • Phenobarbital / therapeutic use
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Retrospective Studies
  • United States


  • Phenobarbital