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Serum intestinal fatty acid binding protein is elevated during feeding advancement in necrotizing enterocolitis

Pediatric Research (2025)Cite this article

Abstract

Background

In retrospective studies, intestinal fatty acid binding protein (I-FABP) has been suggested as a potential biomarker to identify NEC prior to clinical diagnosis. We hypothesize that increasing I-FABP levels with feeding advancement may be a biomarker of intestinal stress prior to clinical suspicion of NEC.

Methods

Prospective study of neonates ≤ 32-week gestation and ≤1500 grams enrolled within 72 h of life. Blood was obtained for biomarker assessment with feeding advancement. ELISA was used to assay serum I-FABP (sI-FABP).

Results

Of 96 patients enrolled, 9 were diagnosed with NEC. sI-FABP values remained low in healthy controls and NEC patients at the initial stages of feeding, up to 60 mL/kg/day. In those who developed NEC, there was a significantly higher sI-FABP at the final sample compared to their own earlier samples (p < 0.0001) or matched controls (p < 0.001). Those who developed NEC while feed volumes were being increased had a significantly higher sI-FABP than others. Receiver operating characteristic (ROC) curve analysis identified sI-FABP of 4.8 ng/mL to be predictive of early NEC with 80% sensitivity and 100% specificity (AUC 0.92; p < 0.01).

Conclusion

Elevation in sI-FABP with increasing volume of enteral feeds correlates with, and precedes, clinical suspicion of NEC.

Impact

  • Serum intestinal fatty acid binding protein elevation during feeding advancement is a sensitive and specific biomarker for necrotizing enterocolitis that precedes clinical suspicion.

  • Early and accurate identification of infants at risk for necrotizing enterocolitis prior to development of symptoms allows the identification of patients at risk that may benefit from early intervention or trial of potential therapies.

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Fig. 1: Study enrollment flowchart.
Fig. 2: Initial vs. Final sI-FABP (ng/mL).
Fig. 3: sI-FABP (ng/mL) vs. Feed Volume (mL/kg/day).
Fig. 4: sI-FABP ROC Curve.

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References

  1. Dominguez, K. M. & Moss, R. L. Necrotizing enterocolitis. Clin. Perinatol. 39, 387–401 (2012).

    Article  PubMed  Google Scholar 

  2. Rich, B. S. & Dolgin, S. E. Necrotizing enterocolitis. Pediatr. Rev. 38, 552–559 (2017).

    Article  PubMed  Google Scholar 

  3. Battersby, C., Santhalingam, T., Costeloe, K. & Modi, N. Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review. Arch. Dis. Child Fetal Neonatal Ed. 103, F182–F189 (2018).

    Article  PubMed  Google Scholar 

  4. Denning, N. L. & Prince, J. M. Neonatal intestinal dysbiosis in necrotizing enterocolitis. Mol. Med 24, 4 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ibrahim, N. R., Van Rostenberghe, H., Ho, J. J. & Nasir, A. Short versus long feeding interval for bolus feedings in very preterm infants. Cochrane Database Syst. Rev. 8, CD012322 (2021).

    PubMed  Google Scholar 

  6. Morgan, J., Young, L. & McGuire, W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst. Rev. 12, CD001970 (2014).

  7. Neu, J. & Pammi, M. Pathogenesis of Nec: impact of an altered intestinal microbiome. Semin Perinatol. 41, 29–35 (2017).

    Article  PubMed  Google Scholar 

  8. Hsueh, W. et al. Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr. Dev. Pathol. 6, 6–23 (2003).

    Article  PubMed  Google Scholar 

  9. Jones, I. H. & Hall, N. J. Contemporary outcomes for infants with necrotizing enterocolitis-a systematic review. J. Pediatr. 220, 86–92.e83 (2020).

    Article  PubMed  Google Scholar 

  10. Lieberman, J. M., Sacchettini, J., Marks, C. & Marks, W. H. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 121, 335–342 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Relja, B. et al. Intestinal-Fabp and Liver-Fabp: novel markers for severe abdominal injury. Acad. Emerg. Med 17, 729–735 (2010).

    Article  PubMed  Google Scholar 

  12. Gollin, G., Marks, C. & Marks, W. H. Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel. Surgery 113, 545–551 (1993).

    CAS  PubMed  Google Scholar 

  13. Zamora, I. J. et al. Low abdominal nirs values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis. PLoS One 10, e0125437 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schurink, M. et al. Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study. PLoS One 10, e0121336 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mannoia, K. et al. Necrotizing enterocolitis is associated with neonatal intestinal injury. J. Pediatr. Surg. 46, 81–85 (2011).

    Article  PubMed  Google Scholar 

  16. Shaaban, A. I. E., Alfqy, O. A. E., Shaaban, H. M. K., YH, A. M. & Assar, E. H. Potential role of serum intestinal fatty acid-binding protein as a marker for early prediction and diagnosis of necrotizing enterocolitis in preterm neonates. J. Indian Assoc. Pediatr. Surg. 26, 393–400 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Aydemir, C. et al. Serum intestinal fatty acid binding protein level for early diagnosis and prediction of severity of necrotizing enterocolitis. Early Hum. Dev. 87, 659–661 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Viswanathan, S., Merheb, R., Wen, X., Collin, M. & Groh-Wargo, S. Standardized slow enteral feeding protocol reduces necrotizing enterocolitis in micropremies. J. Neonatal Perinat. Med. 10, 171–180 (2017).

    Article  CAS  Google Scholar 

  19. Dako, J. et al. Slow enteral feeding decreases risk of transfusion associated necrotizing enterocolitis. J. Neonatal Perinat. Med. 11, 231–239 (2018).

    Article  CAS  Google Scholar 

  20. Dorling, J. et al. Two speeds of increasing milk feeds for very preterm or very low-birthweight infants: the SIFT RCT. Health Technol. Assess. 24, 1–94 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Abiramalatha, T., Thomas, N. & Thanigainathan, S. High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants. Cochrane Database Syst. Rev. 3, CD012413 (2021).

    PubMed  Google Scholar 

  22. Sbragia, L. et al. Intestinal fatty acid-binding protein as a marker of necrotizing enterocolitis incidence and severity: a scoping review. J. Surg. Res. 303, 613–627 (2024).

    Article  CAS  PubMed  Google Scholar 

  23. Edelson, M. B. et al. Plasma intestinal fatty acid binding protein in neonates with necrotizing enterocolitis: a pilot study. J. Pediatr. Surg. 34, 1453–1457 (1999).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank our colleagues from the Ohio Perinatal Research Network who contributed significantly to patient recruitment and sample/data collection for the study: No financial assistance was received in support of this study.

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Authors and Affiliations

  1. Center for Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, USA

    Sophia G. Hameedi, Jessica G. Wright, Carly G. Schafer & Oluyinka O. Olutoye

  2. Division of Pediatric Surgery, Ribeirão Preto Medical School, University of São Paulo, Sao Paulo, Brazil

    Lourenço Sbragia

  3. Department of Pediatric Surgery, Nationwide Children’s Hospital, Columbus, OH, USA

    Oluyinka O. Olutoye

  4. Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, USA

    Oluyinka O. Olutoye

Authors
  1. Sophia G. Hameedi
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  2. Jessica G. Wright
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  3. Carly G. Schafer
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  4. Lourenço Sbragia
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  5. Oluyinka O. Olutoye
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Contributions

S.H. conceptualization, methodology, validation, formal analysis, investigation, writing—original draft, writing—review and editing, visualization. J.W. writing—original draft, writing—review & editing. C.S. investigation, data curation. L.S. conceptualization, writing—original draft, writing–review & editing, supervision. O.O.O. conceptualization, methodology, validation, resources, writing—original draft, writing—review & editing, supervision.

Corresponding author

Correspondence to Oluyinka O. Olutoye.

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The authors declare no competing interests.

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Informed consent was obtained for all subjects enrolled in this study.

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Hameedi, S.G., Wright, J.G., Schafer, C.G. et al. Serum intestinal fatty acid binding protein is elevated during feeding advancement in necrotizing enterocolitis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04614-9

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