Precision Therapeutics in the NICU: Why are We Missing the Mark?
As a field, neonatology has made incredible strides in the past 50 years. The most critically ill infants have increased survival and improved overall outcomes. But with these continued advances there is a threatened sense of complacency, or feeling that we “know” what we are doing in the neonatal intensive care unit (NICU). I propose that when it comes to neonatal pharmacotherapy, our knowledge is lacking and we can do better. As a profession, we must acknowledge the great and unpredictable variability in drug efficacy and toxicity for many of the drug classes we use (e.g., nonsteroidal anti-inflammatory drugs, glucocorticoids, opiates, barbiturates, etc.). We must ask ourselves if we are satisfied with continuing to use these medications without sufficient study, or are we willing to perform the difficult research, which will keep our field on the cutting edge of optimized patient care.
Weight-based dosing has been the standard of care for drug treatment in pediatrics. For certain classes of medication, we have added nuances of gestational age and postmenstrual age to the dosing schemes. And rarely, we have modified dosing algorithms further with known disease and therapeutic considerations (e.g., gentamicin dosing in hypoxic ischemic encephalopathy with therapeutic cooling). But compared to other fields, we are lacking in individualized markers to guide drug treatment. The reasons for the lagging behind of nuanced drug studies in neonates is multi-faceted, but include (1) neonates being considered a “high-risk” population for research and having relatively low patient numbers for any given disease, and thus avoided by pharmaceutical companies, (2) difficulties in recruitment/consent from overwhelmed families, (3) limited blood sampling options for pharmacokinetic (PK) studies, (4) lack of well-validated clinical end points for drug studies, and (5) early loss of equipoise and adoption of drug therapies without rigorous study, among others. In addition, few neonatologists and pediatricians have the formal pharmacology training that sheds a bright light on the deficits in our knowledge and provides the skills to systematically study currently used and novel drug therapies.
Read the full article via The Journal of Perinatology.