677 - Objective Trends in Necrotizing Enterocolitis (NEC) and Probiotic Use Utilizing Epic's Cosmos dataset

Publication Number: 1654.677

Thomas Nienaber, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, United States; Greg P. Muthig, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Kevin Dysart, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Lindsey A. Knake, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States; Evan Miller, Nemours Children's Hospital, Newark, DE, United States; Sara Handley, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Heather Burris, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Jennifer F. Culhane, Yale School of Medicine, New Haven, CT, United States; Jae H.. Kim, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Background: Necrotizing enterocolitis (NEC) affects 5-10% of very low birth weight infants and carries high mortality. RCTs suggest probiotics reduce NEC and death, but the AAP advises caution due to safety concerns. In Sept 2023, the FDA warned against probiotic use in preterm infants, prompting changes in NICU practices. This study assesses shifts in probiotic use and NEC rates following the advisory.

Objective: To assess changes in probiotic use and NEC rates following the FDA's September 2023 advisory. Primary goals include quantifying shifts in probiotic administration and NEC incidence, and evaluating associations of probiotic use with NEC and mortality.

Design/Methods: We used Epic Cosmos, a large deidentified dataset with 1,809 hospitals contributing, to identify infants < 34 weeks or < 1500g born between 2017-2025. An interrupted time series (ITS) analysis with segmented regression assessed monthly rates of and changes in hospital departments' probiotic use and NEC (any stage via ICD codes). NEC-related death, and overall mortality were also assessed over time.

Results: 297,465 infants met inclusion criteria; 18,731 had NEC and 14,387 received probiotics. From 2017-2023, probiotic use rose from 4.4% to 6.9% (p < 0.001), with hospital departments using probiotics increasing from 88 to 228; while NEC rates rose from 5.8% to 6.7% (p < 0.001). After the 2023 FDA advisory, probiotic use dropped to 0.7% in 2024 (p < 0.001), while NEC rates slightly increased to 6.9% (p = 0.159). Of 1109 departments, 548 had stable NEC rates post-advisory, 165 increased, 224 decreased, and 172 lacked sufficient data after 2023. Among NEC cases, odds of death were slightly higher with probiotics (OR 1.3; 95% CI: 1.1-1.7; p = 0.003). No significant change in NEC or NEC/death combined.

Conclusion(s): To date, this is the largest dataset to have been used to assess the correlation between NEC and probiotic use. Following the FDA's September 2023 advisory, probiotic use in preterm infants declined sharply. Despite this, most hospital departments did not experience a statistically significant rise in necrotizing enterocolitis (NEC), mortality, or the composite outcome of NEC or death. However, a subset of departments did report increased NEC rates, suggesting that other contributing factors may have a greater influence on NEC than probiotics. These findings indicate no consistent association between probiotic use and NEC prevention. Further research should explore alternative risk factors and support development of regulated probiotic formulations for neonatal care.

Temporal Trends in Birthweight, NEC and Probiotics
Figure 1. showing the birthweight distribution for the cohort (panel A), the rate of necrotizing enterocolitis overtime (panel B) and the rate of probiotic usage by birthweight category overtime (panel C). The birthweight distribution is reflective of expected weights for newborns admitted to the Neonatal Intensive Care Unit (NICU).

Monthly NEC and Probiotics Rates
Figure 2. Rate of necrotizing enterocolitis and probiotic usage over time with abrupt decrease in probiotic usage around September 29, 2023. This is the date the FDA issued its Dear Doctor letter regarding the use of probiotics in the neonatal setting.

NEC and Probiotics Rates by post 2023 trajectories
Figure 3. Departmental trajectories for the rate of NEC (orange lines) and probiotics (green lines) after September 29, 2023 (the interruption date shown by the vertical dashed line) were determined using an interrupted time series (ITS) analysis, using 3 month rolling averages for NEC, and shown relative to the number of departments contributing (dashed line with counts on the secondary y axis). The trajectories of Stable, Increasing, or Deceasing are determined in an ITS by the trajectories after the interruption date. 95% confidence intervals are shown by the shaded regions along each solid line.