397 - Exposure to opioids and benzodiazepines in preterm infants with and without major operative procedures

Publication Number: 3384.397

Lena S. Sun, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Jennifer Busse, New York Presbyterian Hospital, New York, NY, United States; Ann Kim, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Aditi Lahiri, Kaiser Permanente Division of Research, Berkeley, CA, United States; Michael W. Kuzniewicz, Kaiser Permanente Northern California, Los Gatos, CA, United States; Shawn Jackson, Boston Children's Hospital, Boston, MA, United States; Caleb Ing, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States

Background: Preclinical studies have shown that exposure to sedative, analgesic and anesthetic agents (SAA) increase the risks of neurotoxicity to the developing brain. In 2016, FDA issued a drug warning regarding repeated and prolonged exposures of SAA in children under age 3 years. Data are lacking in preterm infants, a vulnerable patient group that often receives prolonged exposure to SAA in the Neonatal Intensive Care Unit and when they undergo surgery for life threatening conditions.

Objective: To characterize SAA exposures in preterm infants (PREMIE) and examine differences in exposures between those who had surgery or not.

Design/Methods: Study was approved by IRB at Columbia University Medical Center. A total 756 infants with gestational age (GA) < 32 weeks born between March 2020 to December 2024 were included in the study. The study cohorts were: (1) NICU Preterm Exposed Cohort (NPE): patients who only had SAA in NICU with no surgery, (2) Surgical/Procedural Preterm Exposed Cohort (SPE): patients who had surgery and SAA exposure, (3) NICU Preterm Unexposed to SAA (UE): patients with no SAA exposures. Opioids (OP) and benzodiazepines (BENZO) exposures are expressed as morphine milligram equivalents (MME) and lorazepam milligram equivalents (LME). Outcomes were mortality and length of stay (LOS). Data are presented as means±SD, analyzed by unpaired t (continuous), Chi-square tests (categorical). P< 0.05 was deemed significant.

Results: There were 402 UE and 354 exposed PREMIE (EXP), with 320 NPE and 34 SPE. Patient characteristics are summarized in Table 1. EXP and UE differed in BW (1009.5±425.6 g vs 1184.1±378.2 g), sex, but not in GA, and other demographics. NPEC and SPE did not differ in BW, sex or GA. NPE had more MME OP than SPE, while SPE had more BENZOS LME than NPE.
EXP had longer LOS (88.1±56.3 days) than UE (51.3±29.7 days) But, there were no differences between UE and EXP in mortality. (both 6.2% ). Among PREMIE with SAA exposures, NPE had more cumulative doses of OP, and less BENZO (7.7± 12.9 MME, 2.7± 2.6 LME) than SPE (2.0±1.2 MME, 6.6±8.1 LME) but similar LOS (87.6±56.1 vs 93.3±58.3)

Conclusion(s): In our single center study, 45% of PREMIE received OP and/or BENZO. Differences in the types of SAA drugs exposure between surgical and non-surgical EXP patients may reflect variation in practice between surgical specialty providers and others. Future studies are needed to examine whether they may influence long term neurodevelopmental outcomes in the preterm population.

Patient Characteristics of Preterm Infants
Table 1 PAS 2026.pdfPatient Characteristic