Probiotic Products in Preterm Infants: FDA ConcernsAbout Risks and Sales in Hospital Use

by Jasmine Vo, P3

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By the end of October 2023, the FDA sent a letter to healthcare providers, issuing two warning letters to companies that were marketing their probiotic products illegally as a treatment or prevention product for certain diseases in preterm infants in hospitals.1 There have been concerns about the risk of invasive or potentially fatal diseases and infections for this population after a recent preterm infant death due to use of a certain probiotic as a part of inhospital care. The FDA’s news release also mentions several reported adverse events from probiotics use in infants since 2018. One indication that the probiotics were used for is a condition called necrotizing enterocolitis.

Why are probiotics used in relation to diseases such as necrotizing enterocolitis in the first place? Necrotizing enterocolitis (NEC) is a common disease in neonates, involving inflammation of the lining of the intestinal tract.2,3 It is difficult to treat, and there is a greater risk of developing NEC if the infant is born premature or with a very low birth weight.2 In infants, the use of probiotics has been studied for preventing necrotizing enterocolitis.4 A probiotic is defined as a product that contains live microorganisms such as bacteria or yeast that are intended to have health benefits.5 Because probiotics often contain some of the same microorganisms that live in our gut naturally, also called “good bacteria”, it would be beneficial to replenish them under conditions where the community of microorganisms, or the gut microbiome, might be perturbed.2 A 2017 meta-analysis and systematic review done by Foundation Acta Paediatrica, which looked at probiotic use to prevent NEC, concluded that there was benefit, though individual results varied and there was inconclusive evidence on the particular strains that showed the results.2,4 Clinical use of probiotics have therefore been utilized in hospitals in preterm infants for conditions such as NEC, but no probiotic product exists on the market as an approved drug or biological product for infants of any age.1 Probiotics are usually marketed as dietary supplements or food ingredients, meaning the FDA is not required to regulate it.5 However, depending on the indication, probiotics can be defined as drugs, at which point the product needs an FDA approval.

What specific incidences sparked the recent letters from the FDA? The company Abbott Laboratories has a probiotic product called Similac Probiotic Tri-Blend that they sold for hospital use in preterm infants. As it was not being sold for use as a dietary supplement, rather a product for the prevention or treatment of a disease, it is now considered an unlicensed biological product and unapproved new drug.1 When the FDA compared their product’s marketing materials and intended use as on the company’s website to what it was being sold for in hospitals, they sent the company a warning letter because the probiotic product was now in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Public Health Service Act.1 Additionally, the two of the three main ingredients, B. infantis and S. thermophilus, did not meet the necessary safety requirements, and is considered an adulterated dietary supplement under the FD&C Act as well.1 Abbott Laboratories is now working with the FDA for further corrective actions in addition to discontinuing sales of that product. the choice of treatment. There are safety and manufacturing concerns surrounding the use of live microorganisms in general, along with efficacy concerns and lack of data in such a vulnerable population as preterm infants, hence an importance of FDA oversight. These considerations are highlighted by the recommendation by the American Academy of Pediatrics to not routinely or universally administer probiotics to this population, especially in preterm infants with a birthweight <1000 grams.6