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Immunoglobulin A concentration is lower in mothers’ own milk and infant stool in infants who develop necrotising enterocolitis

Pediatric Research (2025)Cite this article

Abstract

Background

Immunoglobulin A (IgA) binding gut bacteria may modulate necrotising enterocolitis (NEC). In infants <32 weeks gestation exclusively receiving their mother’s own milk (MOM) who either did or did not develop NEC, we explored IgA concentration in MOM and infant stool.

Methods

We quantified IgA and secretory IgA (sIgA) concentration by enzyme linked immunosorbent assay (ELISA). 41 NEC (median onset day 22) and 44 matched control infants, median gestation 25 weeks, contributed 202 MOM and 92 stool samples.

Results

IgA and sIgA in MOM were significantly lower for the first three weeks in infants developing NEC compared to control infants (median IgA 499 μg/ml vs 1261 µg/ml, sIgA 481 µg/ml versus 1023 µg/ml, adjusted p < 0.001 between 0–6 and 7–13 days of life, adjusted p = 0.029 days 14–20). Stool IgA concentration before disease was also significantly lower in NEC infants compared with control infants (262 µg/ml versus 491 µg/ml, p = 0.045), but there was no statistical difference in sIgA.

Conclusion

IgA and sIgA are lower in early MOM (before week 3 of life) received by infants who go on to develop NEC, reflected in lower stool IgA. Potential mechanisms require further elucidation. Targeted use of high IgA donor milk to preterm infants may be beneficial.

Impact

  • This is the first published work that evaluates both milk and stool IgA and sIgA in control preterm infants and those developing NEC and has the benefit of samples taken before disease onset for some infants.

  • In this study, IgA and sIgA are lower in early MOM (before week 3 of life) received by infants who go on to develop NEC, reflected in lower stool IgA.

  • Targeted use of high IgA donor milk to preterm infants may be beneficial.

  • Clinical practice in the interim should focus on maximising fresh MOM delivery to preterm babies.

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Fig. 1: Immunoglobulin A concentrations in MOM received by infants from day 0 to 108.
Fig. 2: Immunoglobulin A in MOM comparing NEC to matched controls.
Fig. 3: Immunoglobulin A concentrations in stool from day 0 to 80.
Fig. 4: Immunoglobulin A in infant stool comparing NEC to matched controls.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgement

N.D.E. and J.E.B. declare institutional research funding from Prolacta Biosciences and Danone Early Life Nutrition, and honoraria from Danone Early Life Nutrition, and Nestle Nutrition Institute. C.J.S. declares receiving lecture honoraria from Nestle Nutrition Institute but has no share options or other conflicts. C.L.G. has obtained a grant from the Human Milk Foundation (HMF), which partly funded this research. The other authors declare that they have no competing interests. C.A.L. is supported by the NIHR Newcastle Biomedical Research Centre.

Author information

Authors and Affiliations

  1. Neonatal Intensive Care Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals (NuTH) NHS Trust, Newcastle, UK

    Claire L. Granger, Nicholas D. Embleton & Janet E. Berrington

  2. Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle, UK

    Claire L. Granger, Andrea C. Masi, Christopher A. Lamb, Lauren C. Beck, Jeremy M. Palmer, Christopher J. Stewart & Janet E. Berrington

  3. Department of Gastroenterology, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals (NuTH) NHS Trust, Newcastle, UK

    Christopher A. Lamb

  4. Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle, UK

    Nicholas D. Embleton

Authors
  1. Claire L. Granger
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  2. Andrea C. Masi
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Contributions

C.L.G., C.A.L., N.D.E., J.M.P., C.J.S. and J.E.B. were responsible for the study concept, design and methodology. Wet lab work was performed by C.L.G. supported by J.M.P. Data analysis and interpretation was led by C.L.G. and A.C.M. and supported by all authors. C.L.G., A.C.M., and J.E.B. drafted the manuscript with subsequent critical revisions and edits from all authors. All authors approved the final manuscript for submission.

Corresponding author

Correspondence to Claire L. Granger.

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Competing interests

The authors declare no competing interests.

Consent

Participants were recruited to an ongoing REC approved sample salvage study (SERVIS Supporting Research in Vulnerable Infants REC 10/H0908/39). No additional consent was required for this study.

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Granger, C.L., Masi, A.C., Lamb, C.A. et al. Immunoglobulin A concentration is lower in mothers’ own milk and infant stool in infants who develop necrotising enterocolitis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04570-4

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