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Morphine biotransformation genes and neonatal clinical factors predicted behaviour problems in very preterm children

Cecil M Y Chau1, Colin J D Ross1, Vann Chau2

  • 1BC Children's Hospital Research Institute, Vancouver, Canada; Pediatrics, University of British Columbia, Vancouver, Canada.

Ebiomedicine
|February 3, 2019
PubMed

Insights

Genetic variations influence morphine

Area of Science:

  • Neonatal care and developmental pediatrics
  • Pharmacogenomics and drug metabolism
  • Child psychology and behavioral science

Background:

  • Children born very preterm exhibit high rates of behavioral problems.
  • Morphine exposure is linked to these behavioral issues.
  • Genetic factors in morphine metabolism may explain individual differences.

Purpose of the Study:

  • To investigate if morphine-biotransformation genotypes impact long-term behavior in very preterm infants.
  • To identify specific genetic variations associated with morphine's behavioral effects.

Main Methods:

  • 198 very preterm infants (24-32 weeks gestation) were monitored until 18 months corrected age.
  • Behavioral outcomes (internalizing, externalizing) were assessed using the Child Behavior Checklist.
  • Relationships between morphine exposure, clinical factors, and gene variants (ABCB1, UGT1A9, COMT, etc.) were analyzed.

Main Results:

  • Neonatal factors and genotypes explained 39% of behavioral variance.
  • UGT1A9 rs17863783 (UGT1A6*4) minor allele: higher morphine exposure correlated with increased internalizing behavior.
  • COMT rs4680 Met/Met genotype: higher morphine exposure predicted more externalizing behavior.

Conclusions:

  • Genetic variations affecting brain morphine levels, alongside neonatal clinical factors, differentially predict internalizing and externalizing behaviors.
  • These findings highlight the role of pharmacogenomics in understanding preterm infant neurodevelopment.
Abstract

Keywords:
BehaviourGeneticsMorphinePainPolymorphismPreterm

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