The Potential Impact of Preemptive Pharmacogenetic Genotyping in the Neonatal Intensive Care Unit.

OBJECTIVE: To evaluate the use of drugs with pharmacogenomic (PGx) guidelines from the Clinical Pharmacogenetics Implementation Consortium in early childhood. STUDY DESIGN: A retrospective observational study of patients admitted to the neonatal intensive care (NICU) between 2005 and 2018 with at least 1 subsequent hospitalization at or after 5 years of age was performed to determine PGx drug exposure. Data regarding hospitalizations, drug exposures, gestational age, birth weight, and congenital anomalies and/or a primary genetic diagnosis were collected. Incidence of PGx drug and drug class exposures was determined and patient specific factors predictive of exposure were investigated. RESULTS: During the study, 19 195 patients received NICU care and 4196 (22%) met study inclusion; 67% received 1-2, 28% 3-4, and 5% 5 or more PGx-drugs in early childhood. Preterm gestation, low birth weight (<2500 g), and the presence of any congenital anomalies and/or a primary genetic diagnosis were statistically significant predictors of Clinical Pharmacogenetics Implementation Consortium drug exposures (P < .01, P < .01, P < .01, respectively). CONCLUSIONS: Preemptive PGx testing in patients in the NICU could have a significant impact on medical management during the NICU stay and throughout early childhood.

A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients.

STUDY OBJECTIVE: Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. DESIGN: We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. MEASUREMENTS AND MAIN RESULTS: Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom-designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3-1.2), GC (1, 0.3-1.3), and GG (0.8, 0.3-1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24-1.07), 0.72 (0.22-0.98), 0.58 (0.3-0.94), (p = 0.67). CONCLUSIONS: These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.

Opportunity for pharmacogenetics testing in patients with sickle cell anemia.

Background: Patients with sickle cell disease (SCD) are exposed to numerous drugs over their lifespan, and many of these drugs have Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for personalized dosing. The authors' aim was to ascertain the number of drugs with CPIC guidelines prescribed to SCD patients. Materials & methods: A search of Indiana University Health affiliated hospitals' electronic medical record identified 957 patients with a diagnosis of SCD. Drugs or drug classes with CPIC actionable guidelines ordered as inpatient and outpatient prescriptions were collected from SCD patients. Results: During the 16-year period, 892 (93%) patients received at least one drug that could have been dosed according to CPIC guidelines. Conclusion: Preemptive pharmacogenetics testing should be considered in SCD patients in order to utilize these data throughout the patient's life.