Probiotics Linked to Decreased Mortality in Preterm Infants

 

• Use of probiotics in neonatal units was associated with decreased mortality in preterm and low-birth-weight infants.
• Rates of necrotizing enterocolitis and late-onset sepsis were not different versus those who did not receive probiotics.
• Incidence of probiotic sepsis was rare.

Use of probiotics in neonatal units was associated with decreased mortality in preterm and low-birth-weight infants, a Canadian retrospective cohort study suggested.

Among 32,667 infants born before 34 weeks' gestation, probiotics were associated with decreased mortality rates (adjusted odds ratio 0.62, 98.3% CI 0.53-0.73), but not decreased rates of necrotizing enterocolitis (aOR 0.92, 98.3% CI 0.78-1.09) or late-onset sepsis (aOR 0.90, 98.3% CI 0.80-1.01), reported Belal Alshaikh, MD, MSCE, of the University of Calgary in Alberta, Canada, and colleagues.

For the 7,401 infants with a birth weight less than 1,000 g, probiotics were also associated with decreased mortality rates (aOR 0.58, 98.3% CI 0.47-0.71), but again not decreased rates of necrotizing enterocolitis (aOR 0.90, 98.3% CI 0.71-1.13) or late-onset sepsis (aOR 1.01, 98.3% CI 0.86-1.18), they wrote in Pediatricsopens in a new tab or window.

Incidence of probiotic sepsis was rare, occurring in 27 infants born before 34 weeks' gestation and 20 infants with a birth weight less than 1,000 g. Three infants with probiotic sepsis died, with the condition deemed a possible cause in two cases.

Despite results from previous meta-analyses showing reductions in necrotizing enterocolitis, mortality, and late-onset sepsis with probiotics in very preterm infants, "the adoption of probiotics among neonatal intensive care units (NICUs) varies because of a lack of pharmaceutical-grade products, low to moderate certainty on efficacy, and potential for harm in the form of probiotic sepsis," Alshaikh and colleagues noted.

Real-world dataopens in a new tab or window also reported cases of probiotic sepsis and mortality in preterm neonates, which led the FDAopens in a new tab or window and Health Canadaopens in a new tab or window to issue warning letters about probiotic use in NICUs.

"Given the importance of making informed decisions about probiotics, reporting of beneficial and harmful associations is essential," the authors wrote.

In a commentary accompanying the studyopens in a new tab or window, Roger Soll, MD, and Erika Edwards, PhD, MPH, both of the University of Vermont in Burlington, noted that "the reported effectiveness of probiotic supplementation in infants less than 1,000 g birth weight and the rare cases of probiotic sepsis give some comfort to those choosing to use available probiotic agents."

"However, the exact species of probiotic and the role of breastfeeding (and possible improvements in how we obtain and feed breast milk to critically ill preterm infants) require further research," they added. "The evidence that we have made little if any improvement in the rates of [necrotizing enterocolitis] over the past decade adds urgency to the efforts to find an effective product that will meet regulatory standards."

For this study, Alshaikh and colleagues included infants born before 34 weeks' gestation and admitted to 33 Canadian Neonatal Network units from January 2016 through December 2022. Infants who were moribund on admission, died within 2 days, were admitted more than 2 days after birth, had major congenital anomalies, or never received enteral feeds were excluded.

Of the 32,667 included infants, 57.5% received probiotics (median gestational age 29 weeks), and 42.5% did not (median gestational age 31 weeks).

Because of the retrospective observational nature of the study, there was risk for potential biases and confounding. In addition, because the study spanned more than 7 years, other strategies may have been introduced within NICUs and influenced mortality or necrotizing enterocolitis rates, Alshaikh and colleagues noted.

Furthermore, probiotic sepsis was defined based on the genera of Bifidobacterium and Lactobacillus, and the database used for the study did not collect information needed to determine the link between strains isolated and probiotics used. Finally, the research team did not have data on race and ethnicity.

Disclosures

The study was funded by the Canadian Institutes of Health Research.

The study authors reported no relevant conflicts of interest.

Soll reported serving as vice president of Vermont Oxford Network, being an unpaid member of the Vermont Oxford Network board of directors, and serving as director of the Vermont Oxford Network for Evidence-Based Practice. Edwards reported receiving grant funding from Vermont Oxford Network.

Primary Source

Pediatrics

Source Reference: opens in a new tab or windowAlshaikh BN, et al "Effectiveness and risks of probiotics in preterm infants" Pediatrics 2025; DOI: 10.1542/peds.2024-069102.

Secondary Source

Pediatrics

Source Reference: opens in a new tab or windowSoll RF, Edwards EM "Safety and efficacy of probiotics for preterm infants" Pediatrics 2025; DOI: 10.1542/peds.2024-069450.

https://www.medpagetoday.com/pediatrics/generalpediatrics/114183