Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates.

Kuzniewicz, M. W., Sun, L. S., Lahiri, A., Jackson, S. S., & Davis, J. M. (2025). Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates.. Journal of Perinatology : Official Journal of the California Perinatal Association.

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.

Last updated on 02/15/2026
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