title: Brain Injury and Development in Preterm Infants Exposed to Fentanyl.
abstract: BACKGROUND
  Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl.
  
  
  OBJECTIVE
  To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants.
  
  
  METHODS
  Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤30 weeks gestational age (mean gestational age 26.9 ± 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age.
  
  
  RESULTS
  Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 µg/kg, interquartile range 1-441 µg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age.
  
  
  CONCLUSIONS
  Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants.
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA ccmcpherson@partners.org.
authors.forename: Christopher
authors.initials: C
authors.lastname: McPherson
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Haslam
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pineda
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rogers
authors.affiliation: Boston Children's Hospital, Boston, MA, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Neil
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Inder
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002657:Child Development / Q000187:drug effects*; D005260:Female; D005283:Fentanyl / Q000009:adverse effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000453:epidemiology; D056784:Leukoencephalopathies / Q000139:chemically induced / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D011247:Pregnancy; D012189:Retrospective Studies
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D005283:Fentanyl
keywords: analgesics; magnetic resonance imaging; neonatal intensive care; opioid analgesics; premature infant