Neonatal morphine exposure in very preterm infants-cerebral development and outcomes

J Pediatr. 2015 May;166(5):1200-1207.e4. doi: 10.1016/j.jpeds.2015.02.012.


Objective: To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood.

Study design: Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine.

Results: At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed.

Conclusions: Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / drug effects*
  • Brain / pathology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Intensive Care Units, Neonatal
  • Intensive Care, Neonatal
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Morphine / adverse effects*
  • Organ Size
  • Regression Analysis
  • Treatment Outcome
  • Victoria


  • Morphine