327 - Exposures of Neonates in the NICU to Opioid Analgesic and Sedative Agents

Lena S. Sun, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; Shawn Jackson, Boston Children's Hospital, Boston, MA, United States; MICHAEL W. KUZNIEWICZ, Kaiser Permanante, Los Gatos, CA, United States; Jonathan Davis, Tufts Medical Center, Boston, MA, United States; Ann Kim, Columbia University, New York, NY, United States; Guohua Li, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States

Background: Neurotoxicity from prolonged or repeated exposures to sedative and anesthetic agents (DRUGS) in the developing brain is well documented in preclinical studies, but the risks of adverse neurodevelopmental (ND) outcome in neonates with such exposures remain unknown. Preterm neonates (PREMIES) with developing brains may be particularly vulnerable to exposure to DRUGS.

Objective: Characterize exposures to opioid analgesic, sedative/anesthetic agents in neonates (NEO) using the PHIS database.

Design/Methods: This study was approved by Columbia University IRB. Data are NICU discharges from 2012 and 2023 in PHIS database. PREMIES included: extreme preterm neonates (EP): < 28 weeks gestational age (GA), very preterm neonates (VP): 28-31 weeks GA, and late preterm (LP): 32-36 weeks GA. Data were analyzed by ANOVA (continuous), Chi-square tests (categorical). Poisson regression analyses assessed GA groups and the outcome variables of interest. R was used for all analyses.

Results: A total 374,018 NEO, with 49.5% (n=185,293) PREMIES and 50.5 % (n=188,725) full term neonates (FT) included for analysis. There were 15.4% (n=28,537) EP, 18.5% (n=34,191) VP, 66.1% (n=188,725) LP. Patient demographic & clinical data are presented in Tables 1 and 2.

Exposure to DRUGS occurred in 35.1% NEO and 62.1% (n=114,970) PREMIES, in 81.3% (n=23,150) EP, 45.6% (n=15,593) VP, and 25.8% (n=31,580) LP. DRUG exposure prevalence was opioids > benzodiazepines (BENZO) > propofol > dexmedetomidine > ketamine. PREMIES were more likely than FT to receive opioids and BENZOS, but not propofol, dexmedetomidine or ketamine. Opioids and BENZO exposures were also gestational-age dependent, with more exposures at younger gestational age. Durations of exposure were 3.3±12.5 days in NEO, 2.6±9.8 days in FT, 4.0 ± 14.7 days in PREMIES, and 12.1±26.5, 3.2±12.7, 2.1±9.8 days among EP, VP and LP, respectively. Durations of exposure were 1.6±10.4 days in NEO, 1.0±7.5 days in FT, 2.1±12.6 days in PREMIES, and 7.4±23.8, 1.7±10.8, 1.0±8.3 days among EP, VP and LP, respectively. DRUGS exposure data are detailed in Table 3.

Conclusion(s): PREMIES have more and longer periods of exposures to opioids and BENZO than FT infants, and the prevalence and durations of exposures were GA-dependent. Thus, PREMIES with the most immature brains may be at greater ND risks from such exposures. These data fill the knowledge gap needed for design of future studies examining ND risks associated with DRUGS exposure in NEO and PREMIES.

Patient Demographic Characteristics
Table 1.pdfSummary of patient demographic data

Patient Clinical Characteristics
Table 2.pdfSummary of patient clinical data

Exposures to Analgesic/Sedative/Anesthetic Agents
Table 3.pdf Summary of exposures to analgesic/sedative/anesthetic agents