title: Predictors of neonatal abstinence syndrome in buprenorphine exposed newborn: can cord blood buprenorphine metabolite levels help?
abstract: BACKGROUND
  Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.
  
  
  METHODS
  Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and tissue samples were collected and analyzed by liquid chromatography-mass spectrometry (LC-MS) for buprenorphine and metabolites. Simple and multiple logistic regressions were used to examine relationships between buprenorphine and buprenorphine metabolite concentrations in cord blood and onset of NAS, need for morphine therapy, and length of stay.
  
  
  RESULTS
  Each increase in 5 ng/ml level of norbuprenorphine in cord blood increases odds of requiring treatment by morphine 2.5 times. Each increase in 5 ng/ml of buprenorphine-glucuronide decreases odds of receiving morphine by 57.7 %. Along with concentration of buprenorphine metabolites, birth weight and gestational age also play important roles, but not maternal buprenorphine dose.
  
  
  CONCLUSIONS
  LC-MS analysis of cord blood concentrations of buprenorphine and metabolites is an effective way to examine drug and metabolite levels in the infant at birth. Cord blood concentrations of the active norbuprenorphine metabolite and the inactive buprenorphine-glucuronide metabolite show promise in predicting necessity of treatment of NAS. These finding have implications in improving patient care and reducing healthcare costs if confirmed in a larger sample.
authors.affiliation: Department of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN USA.
authors.forename: Darshan
authors.initials: D
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN USA.
authors.forename: Stacy
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Pharmacy Practice, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Hagemeier
authors.affiliation: College of Public Health, East Tennessee State University, Johnson City, TN USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Kyle
authors.affiliation: Neonatal Perinatal Medicine, Vanderbilt University Medical Center/Monroe Carell Children's Hospital, 2200 Children's Way, Nashville, TN 37232 USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Pryor
authors.affiliation: Department of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN USA.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Dankhara
authors.affiliation: Department of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN USA.
authors.forename: Piyuesh
authors.initials: P
authors.lastname: Singh
keywords: Buprenorphine; Cord blood; Metabolites; NAS; Neonatal abstinence syndrome