Evidence map›Paper›PMID 40634532›Full record

ArticleMolecular psychiatry2025

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

Nghi M Nguyen, Pranavi Athota, Adrian Flores, Andrew Trease, Daniel Meyer, Vamsi K Singu, Chandan Krishnamoorthy, Victoria L Schaal, Reeyan Bhakat, Kunal Sualy and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Nghi M NguyenDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Pranavi AthotaDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Adrian FloresDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.ORCID http://orcid.org/0009-0006-1481-8948
Andrew TreaseDepartment of Neurological Sciences, UNMC, Omaha, NE, USA.
Daniel MeyerDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Vamsi K SinguDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Chandan KrishnamoorthyDepartment of Nutrition & Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.ORCID http://orcid.org/0000-0001-5909-3107
Victoria L SchaalDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.ORCID http://orcid.org/0000-0002-2868-389X
Reeyan BhakatDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Kunal SualyDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Sathish Kumar NatarajanChild Health Research Institute, Omaha, NE, USA.ORCID http://orcid.org/0000-0001-7491-8592
Kelly StauchDepartment of Neurological Sciences, UNMC, Omaha, NE, USA.
Sowmya V YelamanchiliDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.ORCID http://orcid.org/0000-0003-1530-0527
Gurudutt PendyalaDepartment of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, USA. gpendyala@unmc.edu.ORCID http://orcid.org/0000-0002-7226-7367

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

MidazolamAnimalsAnimals, NewbornAnxietyBehavior, AnimalBrainDisease Models, AnimalDopamineFemaleHypnotics and SedativesMaleNeurodevelopmental DisordersRatsRats, Sprague-DawleyDopamineHypnotics and SedativesMidazolam

Identifiers

PMID40634532
PMCPMC12532581

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.