Sedation with midazolam in the NICU: implications on neurodevelopment

The developing brain, particularly in premature infants, is highly susceptible to environmental and pharmacological influences. Premature neonates often require prolonged stays in the NICU, where midazolam (MDZ), a benzodiazepine, is commonly used as a sedative, despite concerns raised by the FDA in 2016 regarding its potential neurological complications in infants. Understanding the long-term effects of MDZ on these vulnerable patients is hindered by ethical considerations and limited research. This review emphasizes the vulnerability of premature infants to sedation and anesthesia and outlines how early exposure to MDZ can impact brain development at both molecular and behavioral levels, drawing from clinical and preclinical data. Additionally, we highlighted existing knowledge gaps and suggested avenues for further research to better comprehend the enduring consequences of MDZ exposure on neurodevelopment in this population.