Towards personalized medicine in preterm newborns: Morphine analgesia predicted by genotype

Abstract

After preterm birth, newborns are exposed to repetitive stressors of neonatal pain and analgesia is essential. Non-maturational covariates and painful events during their treatment at the neonatal intensive care unit [1]. Respiratory support, surgical interventions, infections, skin breaking and other painful procedures all contribute to the cumulative amount of distress in the early life of preterm infants. Appropriate analgesia to protect these vulnerable patients is obligatory, but remains an important challenge. Randomised controlled trials showed that the routine use of morphine in thefirstweek of life is not beneficial on the short term outcome of preterm ventilated newborns [2,3], and effects on the long term are partly unclear [4,5]. Today, most units treat the preterm newborns pain based on the individual needs based on pain assessment scores. Neonatologists are reluctant to prescribe sedatives and analgesics because of fear for side effects on the developing brain. The use of morphine is highly dependent on treatment centre and local policy [1]. Neonatal analgesia andmorphine use is complicated by the fact that pain is difficult to assess. Large inter-individual variability morphine pharmacokinetics and in the effects of analgesics add to this. The amounts of morphine needed to maintain adequate analgesia in preterm newborns vary widely. Predetermination of appropriate dosing and drugs for individual preterm infants would be a great step forward in the medical care of these patients. Grunau, Carleton and colleagues now published their study in EBioMedicine on the genotypic variance in genes related to morphine biotransformation and their association with the amounts of morphine needed during the neonatal period of life and on the behavioural long-term outcome of these infants [6]. Pharmacogenetics, the study of genetic polymorphisms on the pharmacokinetics and dynamics, has only been of limited value for neonatal care up till now. This is partly caused by the fact that maturational effects are very large and therefore generally accepted as the most important factors in neonatal clinical pharmacology [7]. Pharmacokinetics and dynamics of morphine are highly influenced by post-natalmaturation. Activity ofmetabolizing enzymes, but also opioid receptor expression and related pain sensitivity importantly change with age [8]. The system is however very complex and most data are derived from animal models. Further understanding