Dataset Information

Chronic Midazolam Exposure on Neonates and Long-Term Neurodevelopment

ABSTRACT: About 1 in 10 U.S. newborns are born preterm and often require sedation, which may pose long-term neurodevelopmental risks. This study examined the effects of chronic exposure to midazolam (MDZ), a sedative commonly used in NICUs, using a rodent model. Researchers assessed physical, molecular, biochemical, and behavioral outcomes across development. Results showed that early MDZ exposure led to early childhood growth issues, abnormal weight gain patterns in adulthood (suggesting a risk of binge eating), reduced dopamine release, increased brain inflammation markers, and signs of anxiety and social deficits in adolescence. The study highlights potential long-term impacts of neonatal MDZ use on brain and behavior.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

DISEASE(S): Mixed Disorder As Reaction To Stress

SUBMITTER: Gurudutt Pendyala

LAB HEAD: Dr. Gurudutt N. Pendyala

PROVIDER: PXD062940 | Pride | 2025-10-27

REPOSITORIES: Pride

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

Nguyen Nghi M NM Athota Pranavi P Flores Adrian A Trease Andrew A Meyer Daniel D Singu Vamsi K VK Krishnamoorthy Chandan C Schaal Victoria L VL Bhakat Reeyan R Sualy Kunal K Natarajan Sathish Kumar SK Stauch Kelly K Yelamanchili Sowmya V SV Pendyala Gurudutt G

Molecular psychiatry 20250709 11

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 (N ...[more]

PMID: 40634532

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Project description:BackgroundA very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3-4 years.MethodsWe retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34-42 weeks' postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70-84, 85-100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes.ResultsWe observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85-100 groups (post hoc, p = 0.024).ConclusionsIn VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3-4 years.ImpactIn very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3-4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1-2 years, we used brain metabolite concentrations.

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