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<p>Approximately 1 in 10 U.S. newborns are born preterm (&lt;37 weeks of gestation), facing risks of low birth weight, respiratory and birth deficits often requiring surgery, mechanical ventilation, and prolonged sedation. Such long-term exposure to sedatives in these babies can potentially pose neurodevelopmental risks and can further impact changes later in life. The present study focused on midazolam (MDZ), a benzodiazepine class drug commonly used as sedative in the neonatal intensive care unit (NICU). Using a robust preclinical rodent model mimicking chronic MDZ exposure, we did a comprehensive characterization on the phenotypic, molecular, biochemical, and behavioral outcomes in these exposed neonates across key developmental milestones. Our findings indicate that long-term MDZ exposure during the neonatal period negatively affects physical attributes in early childhood. While adult bodyweights between control and MDZ-exposed rats remain comparable, the MDZ rats exhibit accelerated and robust weight gain, potentially indicating a predisposition for binge eating behavior. Additionally, dopamine release in MDZ-exposed rats is markedly reduced in adulthood. Elevated levels of pro-inflammatory cytokines and growth factors in the brain during adulthood suggest a shift in development due to early MDZ exposure. Further, trends of heightened anxiety-like behavior and reduced social interaction during early adolescence compared to other stages were observed. Collectively, our study provides a comprehensive assessment of how long-term MDZ exposure during neonatal stages impacts outcomes throughout life, laying the foundation for understanding mechanisms that contribute to neurodevelopmental complications associated with long-term MDZ use in neonates.</p>

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Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月9日

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  • Nghi M. Nguyen,
  • Pranavi Athota,
  • Adrian Flores,
  • Andrew Trease,
  • Daniel Meyer,
  • Vamsi K. Singu,
  • Chandan Krishnamoorthy,
  • Victoria L. Schaal,
  • Reeyan Bhakat,
  • Kunal Sualy,
  • Sathish Kumar Natarajan,
  • Kelly Stauch,
  • Sowmya V. Yelamanchili,
  • Gurudutt Pendyala

摘要

Approximately 1 in 10 U.S. newborns are born preterm (<37 weeks of gestation), facing risks of low birth weight, respiratory and birth deficits often requiring surgery, mechanical ventilation, and prolonged sedation. Such long-term exposure to sedatives in these babies can potentially pose neurodevelopmental risks and can further impact changes later in life. The present study focused on midazolam (MDZ), a benzodiazepine class drug commonly used as sedative in the neonatal intensive care unit (NICU). Using a robust preclinical rodent model mimicking chronic MDZ exposure, we did a comprehensive characterization on the phenotypic, molecular, biochemical, and behavioral outcomes in these exposed neonates across key developmental milestones. Our findings indicate that long-term MDZ exposure during the neonatal period negatively affects physical attributes in early childhood. While adult bodyweights between control and MDZ-exposed rats remain comparable, the MDZ rats exhibit accelerated and robust weight gain, potentially indicating a predisposition for binge eating behavior. Additionally, dopamine release in MDZ-exposed rats is markedly reduced in adulthood. Elevated levels of pro-inflammatory cytokines and growth factors in the brain during adulthood suggest a shift in development due to early MDZ exposure. Further, trends of heightened anxiety-like behavior and reduced social interaction during early adolescence compared to other stages were observed. Collectively, our study provides a comprehensive assessment of how long-term MDZ exposure during neonatal stages impacts outcomes throughout life, laying the foundation for understanding mechanisms that contribute to neurodevelopmental complications associated with long-term MDZ use in neonates.