FDA's Probiotic Warning for Preterm Infants: What Happened and Lessons for US and EU Product Makers

What happened: the FDA's 2023 warning on probiotics for preterm infants

Between 27 September and 31 October 2023, the US Food and Drug Administration (FDA) took a series of linked actions on probiotic products sold for use in hospitalised preterm infants. They followed the death of a preterm infant who developed sepsis after receiving a probiotic in hospital.^[2]

Timeline of the FDA actions

This was a targeted action against two products and how they were marketed, not a recall of probiotics in general. FDA’s enforcement report now lists both recalls as terminated.^[5][6]

What the FDA established

The infant death and other adverse events

In its letter to healthcare providers, the FDA said a preterm infant with a birthweight under 1,000 g was given Evivo with MCT Oil (Infinant Health) as part of in-hospital care, developed sepsis caused by Bifidobacterium longum and later died. Genomic sequencing showed the bacterium that caused the sepsis was a genetic match to the bacteria in the product.^[2]

In its 26 October 2023 announcement, the FDA said certain probiotics used in hospitals to prevent necrotising enterocolitis (NEC) “have contributed to invasive disease, including one infant death in 2023”, and have been associated with more than two dozen other reported adverse events in the US since 2018.^[1]

No probiotic is approved as a drug for infants

The FDA stated that it “has not approved any probiotic product for use as a drug or biological product in infants of any age”. Healthcare providers who give live bacteria or yeast to treat, mitigate, cure or prevent a disease must file an Investigational New Drug (IND) application.^[1][2]

What the two warning letters found

Table 1. Products named in the FDA’s 2023 actions

Similac Probiotic Tri-Blend is not an infant formula, and the FDA said this action is not related to its earlier concerns about powdered infant formula.^[1]

What is still unknown

As of 2 November 2026, we found no published FDA conclusion on the following points.

• Other possible deaths. In October 2023 the FDA said it was investigating reports that these products may have contributed to further adverse events, including death.^[1] We found no later FDA statement giving the result, so this article does not state any death count beyond the one the FDA confirmed.
• Full case details. The full clinical details of the fatal case have not been released. ISAPP notes that the public information points to bacteraemia from the probiotic organism itself, which is different from earlier case reports caused by contamination of a product.^[8]
• Which products are still used. A survey of US neonatal units found that 29.1% of 289 units gave prophylactic probiotics to premature infants before the warnings, and that use dropped considerably afterwards.^[13]
• An approved product. No probiotic was approved as a drug or biologic for infants when the FDA acted.^[1] One developer, Infant Bacterial Therapeutics, said in May 2026 that it aimed to submit a Biologics License Application for its Limosilactobacillus reuteri candidate IBP-9414 during 2026.^[14] We found no FDA approval as of 2 November 2026.
• An EU equivalent. We found no EU-level notice equivalent to the FDA’s. European paediatric societies have instead called for “a more nuanced and supportive approach to the use of certain probiotics” in preterm infants.^[9]

General risk analysis: why preterm infants are different

The FDA’s warning letters explain the concern. Preterm infants are physiologically immature, and their gut lining is more permeable, which can let live microorganisms cause opportunistic infections and sepsis.^[3][4] The FDA also notes that bacteraemia and fungaemia caused by probiotic organisms have been reported in the medical literature in very preterm and very low birthweight infants.^[2]

The evidence on benefit is two-sided

The FDA itself acknowledges conflicting data on the safety and effectiveness of probiotics for preventing NEC.^[1] A 2023 network meta-analysis of 106 trials in 25,840 preterm infants found that multiple-strain probiotics were associated with lower all-cause mortality (risk ratio 0.69) and lower severe NEC (risk ratio 0.38) than placebo.^[7] ISAPP adds that no meta-analysis has linked probiotic use in preterm infants to more sepsis, and calls for stringent manufacturing standards for products used in this group.^[8] The American Academy of Pediatrics, quoted by the FDA, does not support routine, universal use in preterm infants, particularly those under 1,000 g.^[2]

These are clinical questions for neonatal teams, not for product makers. What a maker controls is whether the product is safe, made to a pharmaceutical-grade standard and sold only for uses the law allows. This article is not medical advice.

Intended use decides how a probiotic is regulated

United States

Both warning letters turned on intended use, not on a labelling error. Website text, NICU sales handouts and product guides that linked the product to reducing NEC made each product a drug and a biological product, which needs an approved Biologics License Application or an IND.^[3][4] Abbott’s label said the product was “not intended for infants with compromised intestinal permeability”, but the FDA found that its other marketing materials contradicted this.^[4]

The food route was closed too. The FDA said B. infantis Bb-02 is not a dietary ingredient, so in a supplement it needed food additive approval or GRAS status, and it found no basis to treat any use in food for preterm infants as GRAS.^[4] It judged each strain separately: TH-4 was a new dietary ingredient with inadequate safety information for preterm infants.^[4] For how US probiotic claims work on general-population products, see FRL’s guide to probiotic claims in the EU and US.

European Union

EFSA’s qualified presumption of safety (QPS) list covers taxonomic units such as Bifidobacterium and Lactobacillus species for food and feed safety assessments, with qualifications such as checking strains for acquired antimicrobial resistance genes.^[10] It is a safety screen for a taxon, not an authorisation for use in hospitalised preterm infants. Because we found no EU-level rule for this use, check the product’s status in each member state before supplying hospitals there.

Lessons for infant probiotic product makers

• Define the user first. If a customer could give the product to hospitalised preterm infants, treat it as a drug-pathway question. Write the intended population into the specification and sales materials, and decide in advance whether hospital and neonatal channels are in or out.^[1]
• Audit every claim, not just the pack. The FDA used websites, infographics and handouts given to hospital staff as evidence of intended use.^[4]
• Build the safety file at strain level. The FDA assessed Bb-02 and TH-4 separately.^[4] Screen each strain for acquired resistance genes.^[10]
• Prove identity and purity in the finished product. A 2026 study of 15 probiotic supplements and foods for special medical purposes on the Polish market found that few products matched their label counts, and recorded eleven detections of microorganisms not on the label, although none contained pathogens.^[11] FRL’s supplement identity-testing recall analysis covers the same control in other products.
• Label what is in the product. FAO/WHO guidelines recommend declaring the genus, species and strain, the minimum viable count at the end of shelf life, and storage conditions.^[12] See what CFU means and how it is tested.
• Keep the records. Keep batch records and retained samples, so an adverse-event report can be traced to a lot.

Table 2. Checklist for infant probiotic products

For the wider method, see FRL’s steps to identify and validate probiotic microorganisms.

For brands & formulators

Food Research Lab helps probiotic and infant nutrition brands review intended use, strain safety evidence and claims before launch in the US and EU. We map the marketing claims in every channel against the regulatory route, check the strain-level safety file, and set out the identity, purity and viability tests the finished product needs. Start with our regulatory and scientific research service, or see our infant nutrition work.

1. U.S. Food and Drug Administration. (2023, October 26). FDA raises concerns about probiotic products sold for use in hospitalized preterm infants [Press announcement]. https://www.fda.gov/news-events/press-announcements/fda-raises-concerns-about-probiotic-products-sold-use-hospitalized-preterm-infants (cited for: one infant death in 2023, more than two dozen adverse events since 2018, ongoing investigation, no approved probiotic drug for infants, IND requirement, both warning letters, Abbott discontinuing sales, conflicting evidence)
2. U.S. Food and Drug Administration. (2023, September 29). Warning regarding use of probiotics in preterm infants [Dear Healthcare Provider letter]. https://www.fda.gov/media/172606/download (cited for: the fatal case, birthweight under 1,000 g, B. longum sepsis, genomic match, literature reports of bacteraemia and fungaemia, AAP statement)
3. U.S. Food and Drug Administration. (2023, September 28). Infinant Health, Inc formerly Evolve Biosystems Inc. – 667715 [Warning letter]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/infinant-health-inc-formerly-evolve-biosystems-inc-667715-09282023 (cited for: Evivo with MCT Oil marketing for the NICU, unapproved drug and unlicensed biologic, EVC001 as an unsafe food additive, preterm gut permeability)
4. U.S. Food and Drug Administration. (2023, October 24). Abbott Laboratories – 669353 [Warning letter]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/abbott-laboratories-669353-10242023 (cited for: NICU marketing materials and NEC claims, unapproved drug and unlicensed biologic, Bb-02 unsafe food additive and not GRAS for preterm infants, TH-4 new dietary ingredient with inadequate safety information, label disclaimer contradicted)
5. U.S. Food and Drug Administration. (2023). Enforcement report: Recall F-0299-2024, Evivo with MCT Oil, Infinant Health [Recall record, openFDA]. https://api.fda.gov/food/enforcement.json?search=recall_number:%22F-0299-2024%22 (cited for: voluntary Class II recall from 27 September 2023, nine lots, 3,257 cartons, 13 states, reason “unapproved food additive”, status terminated)
6. U.S. Food and Drug Administration. (2023). Enforcement report: Recall F-0328-2024, Similac Probiotic Tri-Blend, Abbott Laboratories [Recall record, openFDA]. https://api.fda.gov/food/enforcement.json?search=recall_number:%22F-0328-2024%22 (cited for: voluntary Class II recall from 31 October 2023, lot 45002IP, 226,650 packets, reason for recall, status terminated)
7. Wang, Y., Florez, I. D., Morgan, R. L., Foroutan, F., Chang, Y., Crandon, H. N., Zeraatkar, D., Bala, M. M., Mao, R. Q., Tao, B., Shahid, S., Wang, X., Beyene, J., Offringa, M., Sherman, P. M., El Gouhary, E., Guyatt, G. H., & Sadeghirad, B. (2023). Probiotics, prebiotics, lactoferrin, and combination products for prevention of mortality and morbidity in preterm infants: A systematic review and network meta-analysis. JAMA Pediatrics, 177(11), 1158–1167. https://doi.org/10.1001/jamapediatrics.2023.3849 (cited for: 106 trials, 25,840 infants, multiple-strain probiotics and mortality RR 0.69 and severe NEC RR 0.38)
8. International Scientific Association for Probiotics and Prebiotics. (2023, October 6; updated 2025, June 21). Probiotic administration in preterm infants: Scientific statement. https://isappscience.org/probiotic-administration-in-preterm-infants-scientific-statement/ (cited for: case details not released, organism versus contamination, no meta-analysis linking probiotics to more sepsis, stringent manufacturing standards)
9. van den Akker, C. H. P., Embleton, N. D., Lapillonne, A., Mihatsch, W. A., Salvatore, S., Canani, R. B., Dinleyici, E. C., Domellöf, M., Guarino, A., Gutiérrez-Castrellón, P., Hojsak, I., Indrio, F., Mosca, A., Orel, R., van Goudoever, J. B., Weizman, Z., Mader, S., Zimmermann, L. J. I., Shamir, R., … Szajewska, H. (2024). Reevaluating the FDA’s warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI. Journal of Pediatric Gastroenterology and Nutrition, 78(6), 1403–1408. https://doi.org/10.1002/jpn3.12204 (cited for: European societies’ call for a more nuanced and supportive approach)
10. EFSA Panel on Biological Hazards. (2025). Update of the list of qualified presumption of safety (QPS) recommended microbiological agents intentionally added to food or feed as notified to EFSA 21: Suitability of taxonomic units notified to EFSA until September 2024. EFSA Journal, 23(1), e9169. https://doi.org/10.2903/j.efsa.2025.9169 (cited for: QPS as a taxon-level safety screen and its strain-level qualifications, including acquired antimicrobial resistance genes)
11. Zawistowska-Rojek, A., Rybak, J., Smoleń, P., Kociszewska, A., Rudnicki-Velasquez, P., Węgrzyńska, K., Zaręba, T., Tyski, S., & Baraniak, A. (2026). Evaluating the quality of selected commercial probiotic products, both dietary supplements and foods for special medical purposes. Foods, 15(2), 373. https://doi.org/10.3390/foods15020373 (cited for: 15 products, few matching label counts, eleven detections of unlabelled microorganisms, no pathogens)
12. Food and Agriculture Organization of the United Nations & World Health Organization. (2006). Probiotics in food: Health and nutritional properties and guidelines for evaluation (FAO Food and Nutrition Paper 85). https://www.fao.org/3/a0512e/a0512e.pdf (cited for: recommended label content: genus, species, strain, minimum viable count at end of shelf life, storage conditions)
13. Wala, S. J., Ragan, M. V., Pryor, E., Canvasser, J., Diefenbach, K. A., & Besner, G. E. (2024). Contemporary use of prophylactic probiotics in NICUs in the United States: A survey update. Journal of Perinatology, 44(5), 739–744. https://doi.org/10.1038/s41372-024-01952-0 (cited for: 29.1% of 289 US NICUs used probiotics before the warnings, and use fell afterwards)
14. Infant Bacterial Therapeutics AB. (2026, May 6). Interim report January 1 – March 31, 2026 [Company release]. https://www.inderes.fi/en/releases/infant-bacterial-therapeutics-ab-publ-interim-report-january-1-march-31-2026 (cited for: the company’s stated plan to submit a BLA for IBP-9414 in 2026; a company statement, not an FDA decision)