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Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants

  • Clinical Research Article
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Abstract

Background

Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective.

Methods

In 36 infants born <32 weeks’ gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06–0.13 mg/mL) vs. high (top tertile, range 0.22–0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age.

Results

Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups.

Conclusion

Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting.

Impact

This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

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Fig. 1: Lactoferrin concentration (mg/mL) assayed in whole human milk by electrochemiluminescence multiplex immunoassay technology.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request and with approval of the IRB.

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Acknowledgements

Ms. Chloe Sermet provided technical assistance.

Funding

This research was funded by Brigham and Women’s Hospital Department of Pediatric Newborn Medicine, Bill and Melinda Gates Foundation Call to Action Grant (OPP1211778), NICHD (K23 HD091390, A.C.C.L.), Brigham & Women’s Hospital Stork Fund, Brigham Research Institute Fund to Sustain Research Excellence, Harvard Clinical and Translational Science Center (National Center for Advancing Translational Science, grants 1UL1TR001102 and 1UL1TR002541).

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Authors and Affiliations

  1. Department of Pediatrics, Division of Newborn Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Agata M. P. Atayde, Sara Cherkerzian, Ingrid Olson, Chloe Andrews, Anne C. C. Lee, Sarbattama Sen, Kaitlin George, Katherine Bell & Mandy B. Belfort

  2. Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Agata M. P. Atayde & Neena R. Kapoor

  3. Harvard Medical School, Boston, MA, USA

    Sara Cherkerzian, Anne C. C. Lee, Sarbattama Sen, Katherine Bell & Mandy B. Belfort

  4. Department of Pediatrics, LRF Mother-Milk-Infant Center of Research Excellence (MOMI CORE), Human Milk Institute (HMI), University of California, San Diego, La Jolla, CA, USA

    Lars Bode

  5. Children’s Hospital, Orange County, University of California, Irvine, CA, USA

    Terrie Inder

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  1. Agata M. P. Atayde
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Contributions

A.M.P.A, N.R.K. and M.B.B conceptualized the study; L.B., S.C., K.B. M.B.B., T.I. and K.D. contributed to data acquisition; S.C. assisted in data analysis; A.M.P.A. wrote the initial manuscript draft; all authors provided critical review and editing of the manuscript and approved the final draft. All authors met the Pediatric Research authorship requirements.

Corresponding author

Correspondence to Mandy B. Belfort.

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Parents provided written informed consent for their infant(s) to participate in the study.

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Atayde, A.M.P., Kapoor, N.R., Cherkerzian, S. et al. Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants. Pediatr Res (2024). https://doi.org/10.1038/s41390-023-03002-5

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