title: Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?
abstract: BACKGROUND
  Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure.
  
  
  OBJECTIVE
  We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life.
  
  
  METHODS
  We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain.
  
  
  RESULTS
  Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general 'average' by Dutch norms.
  
  
  CONCLUSIONS
  Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings.
authors: Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Gerbrich E
authors: GE
authors: van den Bosch
authors: Tonya
authors: T
authors: White
authors: Hanan
authors: H
authors: El Marroun
authors: Sinno H P
authors: SH
authors: Simons
authors: Aad
authors: A
authors: van der Lugt
authors: Jos N
authors: JN
authors: van der Geest
authors: Dick
authors: D
authors: Tibboel
authors: Monique
authors: M
authors: van Dijk
mesh_terms: D000375:Aging; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000187:drug effects*; D002648:Child; D059350:Chronic Pain / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007234:Infant, Premature / Q000254:growth & development*; D008279:Magnetic Resonance Imaging; D008297:Male; D009020:Morphine / Q000009:adverse effects* / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D051381:Rats; D012121:Respiration, Artificial / Q000379:methods*
chemical_list: D009020:Morphine