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Opioid-Related Pharmacogenomic Variants in a Retrospective Cohort of High-Risk Hospitalized Infants

Rabab M Barq1, Shadassa Ourshalimian1, Simran Maggo2

  • 1Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA.

The Journal of Pediatrics
|July 19, 2025
PubMed

Insights

Most high-risk infants carry opioid-related pharmacogenomic variants, differing from general populations. This suggests precision prescribing could improve pain management and reduce adverse effects in pediatric patients.

Area of Science:

  • Pediatric pharmacology
  • Genetics and genomics
  • Precision medicine

Background:

  • Opioid pharmacogenomic (PGx) variants influence drug response and adverse effects.
  • High-risk hospitalized infants may have unique genetic profiles affecting opioid metabolism and efficacy.
  • Understanding PGx variant prevalence is crucial for optimizing pain management in vulnerable pediatric populations.

Purpose of the Study:

  • To determine the frequency of opioid-related PGx variants in high-risk hospitalized infants.
  • To compare these variant frequencies with broader genetic databases.
  • To assess the implications for precision opioid prescribing in infants.

Main Methods:

  • Retrospective cohort study of infants (<1 year) with high-risk conditions.
  • Exome sequencing to identify variants in genes (COMT, DRD2/ANKK1, ABCB1, OPRM1, CYP2B6, CYP2D6) associated with opioid response.
  • Comparison of variant frequencies with the Ensembl genomic database using statistical tests.

Main Results:

  • 81.1% of infants were homozygous for at least one opioid-related PGx variant.
  • Significantly higher homozygosity for ABCB1 variants (rs1045642, rs2032582) and lower for COMT (rs4818) and OPRM1 (rs1799971) compared to Ensembl data.
  • Common metabolizer phenotypes included intermediate and normal for CYP2B6 and CYP2D6.

Conclusions:

  • Most high-risk infants carry at least one opioid-related PGx variant, with frequencies distinct from the general population.
  • Pharmacogenomic-guided opioid prescribing holds potential for optimizing pain management and minimizing adverse events in infants.
  • Further research with larger cohorts and ancestrally matched controls is needed to validate findings and clinical utility.
Abstract

Keywords:
infantsopioidspharmacogenomics

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