Can pharmacogenetics inform morphine dosing in the neonatal intensive care unit? A retrospective evaluation

Acutely ill infants in the neonatal intensive care unit (NICU) present with complex medical conditions necessitating individualized therapeutic strategies. These infants exhibit significant variability in gestational age, birth weight, organ maturity and drug metabolism, increasing the risk of adverse drug reactions. Morphine is commonly prescribed in the NICU and is associated with a wide range of dosing as well as a high risk of adverse events. The objective of this retrospective study was to explore the potential relevance of pharmacogenomics to morphine dosing for our local level III NICU. Infants admitted between March and December 2022 were enrolled. Residual EDTA blood collected during routine clinical care was retrieved, and DNA was extracted for 55 patients. Targeted genotyping was performed to detect the rs1799971G > A variant of OPRM1 and the rs4680 G > A variant of COMT. Morphine dosing details were retrieved from medical records, and they were compared to genotypes. Median morphine oral equivalents per day (mg/kg) trended with OPRM1 genotype: AA, 0.0916 (n = 40); AG, 0.1500 (n = 13); GG, 0.2284 (n = 2). Median morphine oral equivalents and the number of days of treatment trended with COMT genotype: GG, 0.1429 mg/kg, 4 days (n = 17); AG, 0.1231 mg/kg, 6 days (n = 22); AA, 0.0875 mg/kg, 8 days (n = 15). Extremely premature infants required the highest morphine doses for the longest duration. Although statistical significance of these findings was not achieved, our data suggest that further studies are warranted to determine whether pharmacogenomics may be beneficial to individualize morphine dose requirements and improve outcomes for acutely ill infants in the NICU.