Routine supplementation with a multistrain probiotic appears to lead to a reduction in the incidence of necrotizing enterocolitis (NEC) in preterm infants, as shown in a Dutch implementation study.
In a high-risk neonatal intensive care unit (NICU) setting, the incidence of NEC decreased from 11.9 percent to 5.3 percent following the implementation of a multistrain probiotic intervention (adjusted risk ratio [ARR], 0.49, 95 percent confidence interval [CI], 0.34–0.70; p<0.001), reported first author Dr Ceren Imren from Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues. [JAMA Netw Open 2026;9:e2631601]
The result was consistent for medical NEC (ARR, 0.50, 95 percent CI, 0.26–0.95; p=0.03), surgical NEC (ARR, 0.44, 95 percent CI, 0.22–0.88; p=0.02), and fatal NEC (ARR, 0.47, 95 percent CI, 0.26–0.86; p=0.01), as well as among extremely preterm infants (ARR, 0.49, 95 percent CI, 0.34–0.72; p<0.001).
The rate of all-cause mortality remained unchanged after the implementation of the probiotic intervention (from 11.7 percent to 11.5 percent; ARR, 1.06, 95 percent CI, 0.82–1.39; p=0.64). However, non–NEC-associated mortality increased from 7.2 percent to 9.6 percent (ARR, 1.42, 95 percent CI, 1.01–1.98; p=0.04).
“Probiotic implementation was not associated with lower all-cause mortality due to a higher non–NEC-related mortality rate after implementation, which did not appear directly attributable to probiotic use,” Imren and colleagues said.
Late-onset sepsis rate decreased from 40.1 percent in the pre-implementation period to 27.6 percent in the postimplementation period (ARR, 0.72, 95 percent CI, 0.63–0.83; p<0.001), mainly due to fewer culture-negative episodes (17.2 percent vs 7 percent; p<0.001), as the authors pointed out.
“This finding may reflect improved gut barrier function and reduced feeding intolerance and systemic inflammation, leading to fewer episodes of clinical instability without proven infection,” they explained.
The median time to full enteral feeding was 9 days in the pre-implementation period vs 8 days in the postimplementation period (p<0.001), and the incidence of focal intestinal perforation was similar between the two periods (1.3 percent vs 1.1 percent).
One case of probiotic-associated sepsis occurred and coincided with fulminant NEC in an infant, with the blood culture growing Bifidobacterium infantis. The infant died due to severe pulmonary haemorrhage despite intensive support.
“Although causality remains uncertain, the event underscores the importance of careful monitoring,” according to Imren and colleagues.
Strain specificity matters
“Strain specificity is critical when selecting probiotic products for use in NICUs,” wrote Dr Thomas Abrahamsson from Linköping University and Crown Princess Victoria Children’s Hospital, Linköping, Sweden, in an accompanying editorial. [JAMA Netw Open 2026;9:e2631608]
Additionally, “probiotic preparations intended for use in preterm infants have to be manufactured in accordance with good manufacturing practice standards. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has outlined specific quality requirements for probiotic products used in this population,” Abrahamsson continued.
In the Dutch implementation trial, the probiotic formulation contained Bifidobacterium infantis Bb-02, Bifidobacterium lactis BB-12, and Streptococcus thermophilus TH-4. Abrahamsson noted that this specific formulation has been shown to be efficacious in preventing NEC in two independent randomized controlled trials and is among those recommended by ESPGHAN. Furthermore, each production batch used in the implementation programme was accompanied by certification of strain identity, purity, viable counts at the end of shelf life, and antibiotic susceptibility and resistance profiles.
That said, “the study by Imren and colleagues represents an important contribution to the field by evaluating the impact of implementing routine probiotic supplementation in the NICU setting. Their findings underscore that only probiotic strains with demonstrated efficacy in rigorously conducted clinical trials should be implemented in clinical practice,” Abrahamsson said.
The study included 1,413 preterm infants (median gestational age 28 weeks, 52.5 percent male), including 598 in the pre-implementation period and 815 in the postimplementation period. In the postimplementation period, infants received a multistrain probiotic supplement (B. infantis Bb-02, B. lactis BB-12, and S. thermophilus TH-4) as part of enteral feeding.