Aim: Determine whether SNPs of OPRM1 118A>G (asn<sup>40</sup>asp), COMT 472G>A (val<sup>158</sup>met) and ARRB2 8622C>T are associated with morphine rescue in newborns on mechanical ventilation. Materials & methods: This is a pharmacogenetic analysis of a randomized controlled trial in (pre)term newborns (n = 64) at a level III Neonatal Intensive Care Unit (NICU) who received placebo infusion and for whom need and dose for rescue morphine was documented. Results: For OPRM1 and COMT separately, the expected risk for rescue morphine or morphine dose was not significantly increased. However, the combined OPRM1/COMT 'high-risk' genotype lead to a significant association with the need for rescue (OR: 5.12; 95% CI: 1.12-23.3; p = 0.035). No association was found between OPRM1/COMT 'high-risk' genotype and total morphine dose administered. Conclusion: Combined OPRM1 118A>G and COMT 472G>A genotype might serve as a predictor for the need of rescue morphine in premature and term newborns on mechanical ventilation.

COMT, morphine, newborns, OPRM1, pain, pediatric, pharmacogenetics, ventilation,
Department of Pediatric Surgery

Matić, M, Simons, S.H.P, Lingen, R.A, van Rosmalen, J.M, Elens, L, de Wildt, S.N, … van Schaik, R.H.N. (2014). Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics, 15(10), 1287–1295. doi:10.2217/pgs.14.100