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  • Quality Improvement Article
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Unplanned natural experiment: probiotics prevent necrotizing enterocolitis, a single center quality improvement report

Journal of Perinatology (2025)Cite this article

Subjects

Abstract

Objective

To reduce necrotizing enterocolitis (NEC) in infants born <32 weeks or <1500 g by implementing probiotics protocol using quality improvement (QI) methodology. Probiotics were discontinued following the FDA warning.

Methods

Multidisciplinary team developed an evidence-based protocol and identified key drivers for implementation. Protocol compliance was the process measure. NEC rate was the outcome measure tracked at baseline, during the QI initiative, and after the FDA warning. Death and sepsis were the balancing measures.

Results

Protocol compliance was 84.5%. The baseline NEC rate was 4.6%, decreased in the post-implementation group to 0.6%, then increased following the FDA warning to 3.8% (p = 0.045). Two special cause variations were observed in relation to implementing and discontinuing probiotics. None of the infants who received probiotics died or developed probiotics associated sepsis.

Conclusions

QI initiative safely implemented probiotics and reduced NEC. The regulatory ban of probiotics was associated with a rebound in NEC rate.

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Fig. 1
Fig. 2: P chart for percentage of infants who received probiotics.
Fig. 3: P chart for infants with NEC from 2019 to 2024.
Fig. 4: T chart for days between NEC cases from 2019 to 2024.

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Data availability

The dataset generated and analyzed during the current study is available from the corresponding author upon reasonable request.

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Author information

Authors and Affiliations

  1. Division of Neonatology, CHOC Children’s, Orange, CA, USA

    Anne Denslow, Gina O’Toole, Sue Freck, Rihana Morejon, Beverly Walti, Christine Bixby, Irfan Ahmad & Michel Mikhael

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  1. Anne Denslow
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  2. Gina O’Toole
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  3. Sue Freck
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  4. Rihana Morejon
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  5. Beverly Walti
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  6. Christine Bixby
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  7. Irfan Ahmad
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  8. Michel Mikhael
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Contributions

Ms Denslow and Dr Mikhael conceptualized and designed the study, collected data, analyzed and interpreted the data, drafted the initial manuscript, and critically reviewed and revised the manuscript. Ms. O’Toole participated in the conceptualization of the study design, collected data, interpreted results, and critically reviewed and revised the manuscript. Ms Freck, Ms Morejon, Ms Walti, Dr Bixby, and Dr. Ahmad participated in the conceptualization of the study design and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Michel Mikhael.

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Competing interests

The authors declare no competing interests.

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CHOC’s institutional review board reviewed the project and determined that it did not meet the requirement for human subject research.

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Denslow, A., O’Toole, G., Freck, S. et al. Unplanned natural experiment: probiotics prevent necrotizing enterocolitis, a single center quality improvement report. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02520-w

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