Clinical Edge

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Combination probiotic formulations might improve outcomes in preterm infants

Key clinical point: Some combination probiotic formulations might improve outcomes among preterm, low-birth-weight infants.

Major finding: High-certainty evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56).

Data source: Network meta-analysis of 63 trials involving 15,712 preterm infants.

Disclosures: Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.


Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.


The demonstration of decreased risks of both death and necrotizing enterocolitis (NEC) in randomized placebo-controlled trials of probiotic microbes in very preterm babies is the most compelling case for administration of probiotics to date. Questions remain, including the optimal probiotic microbe(s) and dose for this population. The ideal studies would compare commercially available probiotic products and doses to each other (rather than to placebo). In the absence of these ideal studies, a network meta-analysis is a valuable tool to compare and rank multiple treatments. One of the drawbacks of a network meta-analysis is the assumption that all interventions have similar effects in all populations (an assumption that is challenging given the marked differences in the incidence of NEC between hospitals and populations).

The study conclusion that the combination of at least one Lactobacillus strain and at least one Bifidobacterium strain is most effective in preventing both death and NEC in very preterm infants is consistent with a previous network meta-analysis and with recent recommendations of the European Society for Paediatric Gastroenterology Hepatology and Nutrition and the American Gastroenterological Association.

Administration of probiotics to very preterm infants remains uncommon in many countries, including the United States. Parents of infants with NEC commonly express frustration at the lack of information about this disease and available preventive strategies. Given an intervention with limited evidence of harm and significant evidence of benefit, it is incumbent upon neonatologists to discuss the available evidence with parents and include their wishes in the decision-making process.

Mark A. Underwood, MD, MAS, is a professor of pediatrics and chief of the division of neonatology in the department of pediatrics at the University of California, Davis. He has received honoraria from Abbott and conducted a clinical trial of probiotics that was funded by Evolve Biosystems.