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Updated: Jun 20, 2026

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
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Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment

Nghi M Nguyen1,2,3, Pranavi Athota1, Adrian Flores1

  • 1Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.

Molecular Psychiatry
|July 9, 2025
PubMed

Insights

Neonatal exposure to midazolam (MDZ), a common ICU sedative, can lead to long-term neurodevelopmental issues. This study shows chronic MDZ use in newborns alters physical development, brain chemistry, and behavior into adulthood.

Area of Science:

  • Neonatal pharmacology
  • Neurodevelopmental toxicology
  • Pediatric intensive care

Background:

  • Preterm birth affects 1 in 10 U.S. newborns, increasing risks for surgical interventions, mechanical ventilation, and prolonged sedation.
  • Long-term sedative exposure in neonates may pose significant neurodevelopmental risks with lasting impacts.
  • Midazolam (MDZ), a benzodiazepine, is frequently used for sedation in neonatal intensive care units (NICUs).

Purpose of the Study:

  • To investigate the long-term effects of neonatal midazolam (MDZ) exposure on neurodevelopmental outcomes.
  • To comprehensively characterize phenotypic, molecular, biochemical, and behavioral changes in neonates exposed to MDZ.
  • To establish a preclinical model for understanding MDZ's impact on development across key life stages.

Main Methods:

  • Utilized a preclinical rodent model to simulate chronic midazolam (MDZ) exposure in neonates.
  • Conducted a comprehensive assessment of physical attributes, body weight, and eating behaviors.
  • Analyzed dopamine release, pro-inflammatory cytokine levels, and growth factors in the brain.
  • Evaluated anxiety-like behavior and social interaction across developmental milestones.

Main Results:

  • Neonatal MDZ exposure negatively impacted early physical development and led to accelerated adult weight gain, suggesting binge eating predisposition.
  • Adult MDZ-exposed rats showed significantly reduced dopamine release and elevated pro-inflammatory cytokines and growth factors in the brain.
  • Heightened anxiety-like behavior and reduced social interaction were observed during early adolescence in MDZ-exposed rats.

Conclusions:

  • Long-term midazolam (MDZ) exposure during the neonatal period has profound and lasting effects on physical, biochemical, and behavioral outcomes.
  • Early MDZ exposure may predispose individuals to altered eating behaviors, reduced dopamine function, and neuroinflammation.
  • Findings provide a foundation for understanding the mechanisms underlying neurodevelopmental complications associated with neonatal sedative use.

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