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

Agata M P Atayde; Neena R Kapoor; Sara Cherkerzian; Ingrid Olson; Chloe Andrews; Anne C C Lee; Sarbattama Sen; Lars Bode; Kaitlin George; Katherine Bell; Terrie Inder; Mandy B Belfort

doi:10.1038/s41390-023-03002-5

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

Pediatr Res. 2024 Jan 8. doi: 10.1038/s41390-023-03002-5. Online ahead of print.

Authors

Agata M P Atayde^{1

2}, Neena R Kapoor², Sara Cherkerzian^{1

3}, Ingrid Olson¹, Chloe Andrews¹, Anne C C Lee^{1

3}, Sarbattama Sen^{1

3}, Lars Bode⁴, Kaitlin George¹, Katherine Bell^{1

3}, Terrie Inder⁵, Mandy B Belfort^{6

7}

Affiliations

¹ Department of Pediatrics, Division of Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA.
² Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Harvard Medical School, Boston, MA, USA.
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.
⁵ Children's Hospital, Orange County, University of California, Irvine, CA, USA.
⁶ Department of Pediatrics, Division of Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA. mbelfort@bwh.harvard.edu.
⁷ Harvard Medical School, Boston, MA, USA. mbelfort@bwh.harvard.edu.

PMID: 38191822
DOI: 10.1038/s41390-023-03002-5

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.