706 - Efficacy of Prophylactic Probiotics on Preventing Necrotizing Enterocolitis in Small for Gestational Age Neonates: A Systematic Review

Publication Number: 706.4586

Neel B. Patel, Rowan-Virtua School of Osteopathic Medicine, Woodbury, NJ, United States; Simran Gandhi, Rowan-Virtua School of Osteopathic Medicine, East Brunswick, NJ, United States; Ravij Upadhyay, Rowan-Virtua School of Osteopathic Medicine, Union, NJ, United States; Katherine Klein, Rowan- Virtua School Of Osteopathic Medicine, Manasquan, NJ, United States; Eric Eichenwald, Children’s Hospital of Philadelphia, Philadelphia, PA, United States

Background: Necrotizing Enterocolitis (NEC) remains a leading cause of morbidity and mortality in preterm neonates. While prophylactic probiotics have been suggested as a preventive measure, their efficacy in high-risk neonates, classified as small for gestational age (SGA) or < 1000 g at birth, as well as the optimal method of administration remains uncertain.

Objective: Our objective was to assess the efficacy of prophylactic probiotics in preventing NEC. Our secondary objective was to perform subgroup analyses based on the method of probiotic delivery and to evaluate efficacy in specific neonatal populations, including those with birth weight < 1000 g and those classified as SGA.

Design/Methods: We conducted a systematic review and meta-analysis using online databases including PubMed, Embase, and Scopus. The studies selected were randomized controlled trials from 1999 to 2024 which examined the incidence of NEC in preterm neonates who received prophylactic probiotics versus placebo. Studies were excluded if they involved non-human trials, were not accessible, or were not in English. Data extracted from each study included probiotic strain type, number of strains used, delivery of probiotics, number of neonates in the control and intervention group, study population weight, and incidence of NEC (Bell Stage >2).

Results: A total of 30 studies, involving 9,121 patients, were included in the analysis. There was a statistically significant reduction in the incidence of NEC with prophylactic probiotics. The overall RR was 0.53 (95% CI [0.42-0.66], p-value = 0.000). There was moderate heterogeneity observed amongst these studies (I2 = 36%). Out of the 30 studies, 29 reported probiotic delivery methods. 9/29 were through breast milk only (NEC RR = 0.48, 95% CI [0.33-0.69], p-Value = 0.000), 2/29 were formula only (NEC RR = 0.41, 95% CI [0.04-4.11], p-Value = 0.440), 14/29 were either or (RR = 0.48, 95% CI [0.34-0.68], p-Value = 0.000), and 2/29 were oral drops (NEC RR = 0.76, 95% CI [0.56-1.02], p-Value = 0.060). 17/30 studies reported neonates < 1000g or SGA separately, making up 26% of the patients included (NEC RR = 0.62, 95% CI [0.46-0.83], p-Value = 0.000).

Conclusion(s): Our systematic review demonstrates that prophylactic probiotics in preterm neonates is associated with a decreased incidence of NEC, including those neonates weighing < 1000 g at birth or those classified as SGA. Probiotics administered through breast milk alone or in combination with formula were associated with lower incidence of NEC.

Overall Effect of Prophylactic Probiotics on NEC Incidence
Figure 1. Forest plot summarizing the overall effect of prophylactic probiotics on the incidence of NEC under a random effects model.

Subgroup Analysis of Probiotic Delivery Methods on NEC Incidence
Figure 2. Subgroup analysis of NEC incidence by probiotic delivery type, comparing different administration methods under a random effects model.

Effect of Prophylactic Probiotics on NEC Prevention in Neonates <1000 g or SGA​
Figure 3. Forest plot showing the effect of prophylactic probiotics on NEC prevention in neonates under 1000 g or classified as small for gestational age (SGA) under a random effects model.

Overall Effect of Prophylactic Probiotics on NEC Incidence
Figure 1. Forest plot summarizing the overall effect of prophylactic probiotics on the incidence of NEC under a random effects model.

Subgroup Analysis of Probiotic Delivery Methods on NEC Incidence
Figure 2. Subgroup analysis of NEC incidence by probiotic delivery type, comparing different administration methods under a random effects model.

Effect of Prophylactic Probiotics on NEC Prevention in Neonates <1000 g or SGA​
Figure 3. Forest plot showing the effect of prophylactic probiotics on NEC prevention in neonates under 1000 g or classified as small for gestational age (SGA) under a random effects model.