title: Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years.
abstract: BACKGROUND
  Extremely low birth weight (ELBW) infants are exposed to many painful procedures while in the neonatal intensive care unit (NICU), such as catheter insertion and endotracheal intubation. Exposure of ELBW infants to repetitive pain and stress in the NICU can lead to cardiovascular instability and may alter neuronal and synaptic organization. Opioid analgesics are administered to reduce pain, stress and to potentially reduce poor neurologic outcomes. They may also be utilized as sedation for mechanically ventilated ELBW infants. There is limited data in regards to neurodevelopmental outcomes of preterm infants exposed to opioids, and available studies have conflicting results.
  
  
  OBJECTIVE
  To examine the relationship between cumulative opioid dose in ELBW infants in the NICU and neurodevelopmental outcomes at 20 months corrected age (CA).
  
  
  METHODS
  100 ELBW infants who had complete neurodevelopmental assessments at 20 months CA were categorized by cumulative opioid exposure during the NICU stay (high vs. low/no opioid). Outcome measures included cognitive, motor and language scores from the Bayley Scales of Infant and Toddler Development-III (BSITD-III). Multiple regression analyses adjusted for the impact of social and neonatal risk factors on outcome.
  
  
  RESULTS
  There were 60 patients with high and 40 with low/no opioid exposure. Infants in the high dose group had a higher number of median ventilator days (53.5 vs. 45.6 days, p=0.046) and a higher incidence of necrotizing enterocolitis (5% vs. 21.7%, p=0.022). There were no significant differences in BSITD-III scores between the two opiate groups. In multivariate analysis cumulative opioid dose was associated with lower cognitive scores on the BSITD-III even after adjusting for social and neonatal risk factors (β=-0.247, p=0.012).
  
  
  CONCLUSIONS
  Cumulative opioid dose is associated with worse cognitive scores at 20 months CA even after adjusting for social and neonatal risk factors.
authors.affiliation: Department of Pharmacy, Rush University Medical Center, 1653 W Congress Pkwy, Room 0036 Atrium, Chicago, IL 60612, United States. Electronic address: Melissa_a_kocek@rush.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kocek
authors.affiliation: Department of Pharmacy, Rush University Medical Center, 1653 W Congress Pkwy, Room 0036 Atrium, Chicago, IL 60612, United States. Electronic address: rogerwilcox@gmail.com.
authors.forename: Roger
authors.initials: R
authors.lastname: Wilcox
authors.affiliation: Department of Pharmacy, Rush University Medical Center, 1653 W Congress Pkwy, Room 0036 Atrium, Chicago, IL 60612, United States. Electronic address: christophercrank@rushcopley.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Crank
authors.affiliation: Department of Pediatrics, Rush University Medical Center, 1653 W Congress Parkway, Pavilion 353, United States. Electronic address: kousiki_patra@rush.edu.
authors.forename: Kousiki
authors.initials: K
authors.lastname: Patra
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000777:Anesthetics / Q000009:adverse effects*; D002657:Child Development / Q000187:drug effects*; D003071:Cognition; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D052577:Infant, Extremely Low Birth Weight / Q000254:growth & development*; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data*; D008297:Male
chemical_list: D000701:Analgesics, Opioid; D000777:Anesthetics
keywords: BSITD-III; ELBW; Neurodevelopment; Opioids; Pain