Related Experiment Video
Updated: Mar 27, 2026
Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants
Emma G Duerden1, Ting Guo1, Lorin Dodbiba1
1Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario.
Insights
Midazolam exposure in preterm neonates was linked to reduced hippocampal growth and poorer cognitive outcomes. Invasive procedures did not show this association, suggesting caution with midazolam use.
Area of Science:
- Neonatal Intensive Care
- Neuroscience
- Developmental Pediatrics
Background:
- Very preterm neonates undergo painful procedures in NICU care.
- Analgesics and sedatives, like opiates and benzodiazepines, are crucial but may impact brain development.
- The hippocampus is particularly vulnerable to these exposures and may influence long-term outcomes.
Purpose of the Study:
- To assess the impact of invasive procedures and analgesic-sedative exposure on hippocampal growth in preterm neonates.
- To determine if hippocampal growth influences neurodevelopmental outcomes.
Main Methods:
- 138 preterm neonates (gestational age 27.7 weeks) underwent MRI and DTI scans at two time points.
- Hippocampal volumes and diffusion measures (axial diffusivity, radial diffusivity, mean diffusivity) were analyzed.
- Cognitive, language, and motor skills were assessed at 18.7 months using Bayley Scales of Infant Development-III.
Main Results:
- Higher midazolam (a benzodiazepine) dose correlated with smaller hippocampal volumes and increased mean diffusivity (microstructural change).
- Invasive procedures did not significantly affect hippocampal volume or diffusion measures.
- Lower cognitive scores were associated with reduced hippocampal growth, midazolam dose, and surgery.
Conclusions:
- Midazolam exposure is associated with hippocampal macro- and microstructural alterations in preterm infants.
- These changes align with hippocampal dysmaturation and predict poorer neurodevelopmental outcomes.
- Caution is advised regarding midazolam use in preterm neonates, especially those not undergoing surgery.
Objective:
Very preterm-born neonates (24-32 weeks of gestation) are exposed to stressful and painful procedures during neonatal intensive care. Analgesic and sedation therapies are essential, and opiates and benzodiazepines are commonly used. These medications may negatively impact brain development. The hippocampus may be especially vulnerable to the effects of pain and analgesic and/or sedative therapies and contribute to adverse outcomes. The effect of invasive procedures and analgesic-sedative exposure on hippocampal growth was assessed, as was that of hippocampal growth on neurodevelopmental outcome.
Methods:
A total of 138 neonates (51% male, median gestational age = 27.7 weeks) underwent magnetic resonance imaging and diffusion tensor imaging (DTI) scans, early in life (postmenstrual age [PMA] = 32.3 weeks) and at term-equivalent age (PMA = 40.2 weeks). Volumes and DTI measures of axial diffusivity, radial diffusivity, and mean diffusivity (MD) were obtained from the hippocampus. Cognitive, language, and motor abilities were assessed using the Bayley Scales of Infant Development-III at 18.7 months median corrected age. Models testing the association of invasive procedures with hippocampal volumes and DTI measures accounted for birth gestational age, sex, PMA, dose of analgesics/sedatives (fentanyl, morphine, midazolam), mechanical ventilation, hypotension, and surgeries.
Results:
Total midazolam dose predicted decreased hippocampal volumes (β = -1.8, p < 0.001) and increased MD (β = 0.002, p = 0.02), whereas invasive procedures did not (β = 0, p > 0.5 each). Lower cognitive scores were associated with hippocampal growth (β = -0.31, p = 0.003), midazolam dose (β = -0.27, p = 0.03), and surgery (β = -8.32, p = 0.04).
Interpretation:
Midazolam exposure was associated with macro- and microstructural alterations in hippocampal development and poorer outcomes consistent with hippocampal dysmaturation. Use of midazolam in preterm neonates, particularly those not undergoing surgery, is cautioned.
More Related Videos
05:13Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes
Published on: February 28, 2025
15:27Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development
Published on: July 13, 2014
Related Concept Videos
01:29Drug Dosing: Infants and Children
01:19Sedatives and Hypnotics Drugs: Benzodiazepines
Benzodiazepines work by enhancing the effects of the inhibitory neurotransmitter GABA. They bind to the GABAA receptor, increasing its affinity for GABA, which opens chloride...
01:21Factors Affecting Drug Response: Overview
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...