Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns

Subjects

Abstract

Objectives:

Lactoferrin (LF) is a breast milk glycoprotein with protective effects against neonatal infections, mainly in premature and low-birth-weight (LBW) neonates. The aims of this study were to determine LF concentration in breast milk of mothers of LBW infants during the first 2 months postpartum, and to identify the factors associated with LF concentration.

Study Design:

Prospective study conducted as a part of an ongoing clinical trial in three Neonatal Units in Peru. We included 346 mothers of neonates with a birth weight <2000 g. We measured LF concentration in four stages of lactation using a commercial enzyme-linked immunosorbent assay kit. Multivariate analysis was performed to assess the association between maternal and neonatal factors, and LF concentration.

Results:

We collected 695 milk samples. LF mean concentration±standard deviation was 14.92±7.96 mg ml−1 in colostrum (n=277), 10.73±5.67 in transitional milk (n=55), 10.34±6.27 at 1 month (n=259) and 8.52±6.47 at 2 months (n=104). There was a significant difference in LF concentration between different stages of lactation (P<0.001). Mothers with higher LF concentration in colostrum had higher values in the following 2 months. High maternal income and multiple gestation were significantly associated with higher LF levels; in contrast, maternal peripartum infections and male neonatal gender were associated with lower LF levels.

Conclusions:

LF concentration in breast milk of mothers of LBW infants was high and remained elevated even at 1 and 2 months postpartum. LF concentration in colostrum was higher in mothers with higher income and multiple pregnancies, and lower in mothers with peripartum infections.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Stoll BJ .The global impact of neonatal infection.Clin Perinatol 1997; 24: 1–21.

    Article  CAS  Google Scholar 

  2. Shane AL, Stoll BJ .Neonatal sepsis: progress towards improved outcomes.J Infect 2014; 68 (Suppl 1): S24–S32.

    Article  Google Scholar 

  3. Ferreira RC, Mello RR, Silva KS .Neonatal sepsis as a risk factor for neurodevelopmental changes in preterm infants with very low birth weight.J Pediatr (Rio J) 2014; 90: 293–299.

    Article  Google Scholar 

  4. van Vliet EOG, de Kieviet JF, Oosterlaan J, van Elburg RM .Perinatal infections and neurodevelopmental outcome in very preterm and very low-birth-weight infants: a meta-analysis.JAMA Pediatr 2013; 167: 662–668.

    Article  Google Scholar 

  5. Dong Y, Speer CP .Late-onset neonatal sepsis: recent developments.Arch Dis Child Fetal Neonatal Ed 2015; 100: F257–F263.

    Article  Google Scholar 

  6. Underwood MA .Human milk for the premature infant.Pediatr Clin North Am 2013; 60: 189–207.

    Article  Google Scholar 

  7. Furman L, Taylor G, Minich N, Hack M .The effect of maternal milk on neonatal morbidity of very low-birth-weight infants.Arch Pediatr Adolesc Med 2003; 157: 66–71.

    Article  Google Scholar 

  8. Vogel HJ .Lactoferrin, a bird’s eye view.Biochem Cell Biol 2012; 90: 233–244.

    Article  CAS  Google Scholar 

  9. Embleton ND, Berrington JE, McGuire W, Stewart CJ, Cummings SP .Lactoferrin: antimicrobial activity and therapeutic potential.Semin Fetal Neonatal Med 2013; 18: 143–149.

    Article  Google Scholar 

  10. Ochoa TJ, Cleary TG .Effect of lactoferrin on enteric pathogens.Biochimie 2009; 91: 30–34.

    Article  CAS  Google Scholar 

  11. Turin CG, Zea-Vera A, Pezo A, Cruz K, Zegarra J, Bellomo S et al.Lactoferrin for prevention of neonatal sepsis.Biometals 2014; 27: 1007–1016.

    Article  CAS  Google Scholar 

  12. Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H et al.Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial.JAMA 2009; 302: 1421–1428.

    Article  CAS  Google Scholar 

  13. Akin IM, Atasay B, Dogu F, Okulu E, Arsan S, Karatas HD et al.Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells.Am J Perinatol 2014; 31: 1111–1120.

    Article  Google Scholar 

  14. Ochoa TJ, Zegarra J, Cam L, Llanos R, Pezo A, Cruz K et al.Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g.Pediatr Infect Dis J 2015; 34: 571–576.

    Article  Google Scholar 

  15. Pammi M, Abrams SA .Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants.Cochrane Database Syst Rev 2015; 2: CD007137.

    Google Scholar 

  16. Sherman MP, Adamkin DH, Niklas V, Radmacher P, Sherman J, Wertheimer F et al.Randomized controlled trial of talactoferrin oral solution in preterm infants.J Pediatr 2016; 175 (68–73): e3.

    Google Scholar 

  17. Barrington KJ, Assaad M-A, Janvier A .The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant.J Perinatol 2016; 36: 666–669.

    Article  CAS  Google Scholar 

  18. Ballard O, Morrow AL .Human milk composition: nutrients and bioactive factors.Pediatr Clin North Am 2013; 60: 49–74.

    Article  Google Scholar 

  19. Rai D, Adelman AS, Zhuang W, Rai GP, Boettcher J, Lönnerdal B .Longitudinal changes in lactoferrin concentrations in human milk: a global systematic review.Crit Rev Food Sci Nutr 2014; 54: 1539–1547.

    Article  CAS  Google Scholar 

  20. Lönnerdal B, Zavaleta N, Kusunoki L, Lanata CF, Peerson JM, Brown KH .Effect of postpartum maternal infection on proteins and trace elements in colostrum and early milk.Acta Paediatr 1996; 85: 537–542.

    Article  Google Scholar 

  21. Ronayne de Ferrer PA, Baroni A, Sambucetti ME, López NE, Ceriani Cernadas JM .Lactoferrin levels in term and preterm milk.J Am Coll Nutr 2000; 19: 370–373.

    Article  CAS  Google Scholar 

  22. Broadhurst M, Beddis K, Black J, Henderson H, Nair A, Wheeler T .Effect of gestation length on the levels of five innate defence proteins in human milk.Early Hum Dev. 2015; 91: 7–11.

    Article  CAS  Google Scholar 

  23. Goldman AS, Garza C, Nichols BL, Goldblum RM .Immunologic factors in human milk during the first year of lactation.J Pediatr 1982; 100: 563–567.

    Article  CAS  Google Scholar 

  24. Hamosh M .Bioactive factors in human milk.Pediatr Clin North Am 2001; 48: 69–86.

    Article  CAS  Google Scholar 

  25. Dawarkadas AM, Saha K, Mathur NB .A comparative study of cells and anti-microbial proteins in colostrum of mothers delivering pre- and full-term babies.J Trop Pediatr 1991; 37: 214–219.

    Article  CAS  Google Scholar 

  26. Montagne P, Cuillière ML, Molé C, Béné MC, Faure G .Immunological and nutritional composition of human milk in relation to prematurity and mother’s parity during the first 2 weeks of lactation.J Pediatr Gastroenterol Nutr 1999; 29: 75–80.

    Article  CAS  Google Scholar 

  27. Teng CT .Lactoferrin gene expression and regulation: an overview.Biochem Cell Biol 2002; 80: 7–16.

    Article  CAS  Google Scholar 

  28. Hennart PF, Brasseur DJ, Delogne-Desnoeck JB, Dramaix MM, Robyn CE .Lysozyme, lactoferrin, and secretory immunoglobulin A content in breast milk: influence of duration of lactation, nutrition status, prolactin status, and parity of mother.Am J Clin Nutr 1991; 53: 32–39.

    Article  CAS  Google Scholar 

  29. Sanchez-Pozo A, Lopez Morales J, Izquierdo A, Martinez-Valverde A, Gil A .Protein composition of human milk in relation to mothers’ weight and socioeconomic status.Hum Nutr Clin Nutr 1987; 41: 115–125.

    CAS  PubMed  Google Scholar 

  30. Otsuki K, Yoda A, Saito H, Mitsuhashi Y, Toma Y, Shimizu Y et al.Amniotic fluid lactoferrin in intrauterine infection.Placenta 1999; 20: 175–179.

    Article  CAS  Google Scholar 

  31. Pacora P, Maymon E, Gervasi MT, Gomez R, Edwin SS, Yoon BH et al.Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes.Am J Obstet Gynecol 2000; 183: 904–910.

    Article  CAS  Google Scholar 

  32. Leelahakul V, Tanaka F, Sinsuksai N, Vichitsukon K, Pinyopasakul W, Kido N et al.Comparison of the protein composition of breast milk and the nutrient intake between Thai and Japanese mothers.Nurs Health Sci 2009; 11: 180–184.

    Article  Google Scholar 

  33. Prentice A, Prentice AM, Cole TJ, Whitehead RG .Determinants of variations in breast milk protective factor concentrations of rural Gambian mothers.Arch Dis Child 1983; 58: 518–522.

    Article  CAS  Google Scholar 

  34. Breakey AA, Hinde K, Valeggia CR, Sinofsky A, Ellison PT .Illness in breastfeeding infants relates to concentration of lactoferrin and secretory Immunoglobulin A in mother’s milk.Evol Med Public Health 2015; 2015: 21–31.

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to all the members of the NEOLACTO Research Group: Rospigliosi M, MD, Borda G, MD, Webb V, MD, Lino A, MD, Cama A, MD, Llanos R, MD, Chumbes O, MD, Cuba, L, MD, Tresierra J, MD, Chincaro C, MD, Alarcon W, MD, Bravo E, MD, Pacheco K, MD, Guillen D, MD, Medina P, MD, Tori A, MD, Rivas M, MD, Campos M, MD, Tucto L, RN, Suarez C, RN, Huanay M, RN and Rojas N, RN. We also want to express our most sincere gratitude to the volunteer mothers, for their participation and commitment to the project. This work was funded by the National Institute of Child Health & Human Development (NICHD), grant number: R01-HD067694. Clinical Trial Registration: Lactoferrin for Prevention of Sepsis in Infants (NEOLACTO), NCT01525316, web link: https://clinicaltrials.gov/ct2/show/NCT01525316.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to C G Turin.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turin, C., Zea-Vera, A., Rueda, M. et al. Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns. J Perinatol 37, 507–512 (2017). https://doi.org/10.1038/jp.2016.265

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2016.265

Search

Quick links