title: Association of fentanyl with neurodevelopmental outcomes in very-low-birth-weight infants.
abstract: BACKGROUND
  Opioids are commonly used in the neonatal intensive care unit (NICU). Negative neurodevelopmental effects in the short-term setting have been associated with opioids ; however, long-term studies have been limited.
  
  
  OBJECTIVE
  The primary objective was to determine if there is a dose relationship between fentanyl and neurodevelopmental outcomes, as measured by Bayley Scales of Infant and Toddler Development (Bayley-III) composite scores for language, cognition, and motor skills. Secondary objectives included comparison of Bayley-III scores and neurodevelopmental impairment classification based on fentanyl exposure.
  
  
  METHODS
  A retrospective evaluation of 147 very-low-birth-weight infants with Bayley-III scores obtained at a chronological age of 6 months to 2 years at clinic follow-up was conducted. Univariate and multivariable linear regression analyses were used to determine if there was a dose-related association between fentanyl and neurodevelopmental outcomes. To evaluate secondary outcomes, patients were divided based on cumulative fentanyl dose ("high-dose" versus "low/no-dose").
  
  
  RESULTS
  The univariate analysis found a statistically significant decrease in cognition (P = .034) and motor skills scores (P = .006). No association was found in the multi-variable regression between fentanyl cumulative dose and Bayley-III scores. There was a significant decrease in the motor skills score between the high-dose versus low/no-dose group, 94 ± 20 versus 102 ± 15, respectively (P = .026); however, no statistical differences were noted for language or cognition scores or neurological impairment classification.
  
  
  CONCLUSIONS
  When controlling for other variables, the cumulative fentanyl dose did not correlate with neurodevelopmental outcomes. Further evaluation of benefits and risks of opioids in premature infants are needed.
authors: University of Missouri Health Care, Columbia, MO, USA.
authors: Erin M
authors: EM
authors: Lammers
authors: Peter N
authors: PN
authors: Johnson
authors: Kimberly D
authors: KD
authors: Ernst
authors: Tracy M
authors: TM
authors: Hagemann
authors: Shelley M
authors: SM
authors: Lawrence
authors: Patricia K
authors: PK
authors: Williams
authors: Michael P
authors: MP
authors: Anderson
authors: Jamie L
authors: JL
authors: Miller
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005283:Fentanyl / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal; D007804:Language Development; D008137:Longitudinal Studies; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: fentanyl; midazolam; neonate; neurodevelopment; opioid; premature