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Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates

Journal of Perinatology (2025)Cite this article

Subjects

Abstract

Objective

To quantify opioid and benzodiazepine exposure in extremely preterm neonates and assess variation by gestational age, facility, and clinical factors.

Study design

Cross-sectional study of 1501 neonates born at 23–28 weeks gestation at Kaiser Permanente Northern California (2011–2021). Medication data were extracted from electronic records. Cumulative opioid and benzodiazepine exposures were standardized to morphine and lorazepam equivalents per kg. Logistic regression evaluated associations with clinical comorbidities.

Results

Thirty percent of neonates were exposed to both drug classes, 24% to opioids alone, and 1.5% to benzodiazepines alone. Exposure was inversely related to gestational age and varied widely across facilities. High opioid exposure (≥10 MME/kg) was associated with mechanical ventilation (aOR 3.7), vasopressors (aOR 4.6), oxygen at 36 weeks (aOR 1.7), and severe IVH (aOR 2.5).

Conclusions

Opioid and benzodiazepine use is common and variable in extremely preterm neonates. Standardized pain management and long-term outcome studies are urgently needed.

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Fig. 1: Duration of Opioid and Benzodiazepine Use by Gestational Age.
Fig. 2: Cumulative Exposure to Opioids and Benzodiazepines.
Fig. 3: Inter-Facility Variation in Opioid and Benzodiazepine Exposure by Gestational Age.

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Acknowledgements

Funded in part by a grant from the US Food and Drug Administration U01FD007702.

Author information

Authors and Affiliations

  1. Division of Research, Perinatal Research Unit, Kaiser Permanente Northern California, Pleasanton, CA, USA

    Michael W. Kuzniewicz & Aditi Lahiri

  2. Department of Pediatrics, University of California School of Medicine, San Francisco, CA, USA

    Michael W. Kuzniewicz

  3. Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA

    Lena S. Sun

  4. Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA

    Lena S. Sun

  5. Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Shawn S. Jackson

  6. The Department of Pediatrics and the Tufts Clinical and Translational Science Institute, Tufts Medical Center, Boston, MA, USA

    Jonathan M. Davis

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  1. Michael W. Kuzniewicz
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  2. Lena S. Sun
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  4. Shawn S. Jackson
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Contributions

All authors contributed to the: 1. Conception and design of the work. 2. The acquisition, analysis, and interpretation of data. 3. Drafting the work and reviewing it critically for important intellectual content. 4. Final approval of the version to be published.

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Correspondence to Michael W. Kuzniewicz.

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Kuzniewicz, M.W., Sun, L.S., Lahiri, A. et al. Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02513-9

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