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Biologically active breast milk proteins in association with very preterm delivery and stage of lactation



The aim of this study was to identify the independent effect of very preterm gestation on breast milk content of biologically active proteins (secretory immunoglobulin A (sIgA), lysozyme, lactoferrin, osteoprotegerin (OPG), leptin, adiponectin and β-endorphin (b-EP)) during the first month of lactation.

Study Design:

We collected samples of transitional (6 to 8 and 13 to 15 days) and mature (20 to 22 and 27 to 29 days) milk from mothers after term (38 to 41 weeks) or very preterm (24 to 31 weeks) delivery. The levels of sIgA, lysozyme, lactoferrin, OPG, leptin, adiponectin and b-EP in the breast milk were quantified using enzyme-linked immunosorbent assay or enzyme immunoassay kits. Statistical analysis included descriptive statistics and regression analysis.


Sixty breast milk samples were collected from 15 mothers after very preterm (preterm breast milk, PBM) and 20 samples from 5 mothers after term (term breast milk, TBM) deliveries. Decrease in lysozyme, lactoferrin, OPG, leptin, adiponectin and b-EP but no change in sIgA was recorded during the first month of lactation in both TBM and PBM. The IgA, lysozyme and adiponectin were higher in PBM than in TBM, whereas concentrations of lactoferrin, OPG and leptin were higher in TBM than in PBM (P<0.05 to 0.0001). A similar pattern was seen in the lysozyme, leptin and adiponectin concentration in mature milk. Increased b-EP levels in breast milk were associated with the vaginal mode of delivery but not gestational age.


Although a similar pattern of change was observed in the breast milk bioactive proteins during the first month of lactation after term and very preterm gestation, PBM is a better source of factors with antibacterial/anti-inflammatory activities but is constantly deficient in leptin, which is involved in neuroendocrine regulation.

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  1. American Academy of Pediatrics. Breastfeeding and the use of human milk. Work group on breastfeeding. Pediatrics 1997; 100: 1035–1039.

    Article  Google Scholar 

  2. Resto M, O’Connor D, Leef K, Funanage V, Spear M, Locke R . Leptin levels in preterm human breast milk and infant formula. Pediatrics 2001; 108: E15.

    Article  CAS  Google Scholar 

  3. Zanardo V, Nicolussi S, Carlo G, Marzari F, Faggian D, Favaro F et al. Beta endorphin concentrations in human milk. J Pediatr Gastroenterol Nutr 2001; 33: 160–164.

    Article  CAS  Google Scholar 

  4. Martin LJ, Woo JG, Geraghty SR, Altaye M, Davidson BS, Banach W et al. Adiponectin is present in human milk and is associated with maternal factors. Am J Clin Nutr 2006; 83: 1106–1111.

    Article  CAS  Google Scholar 

  5. Goldman A, Garza C, Nichols B, Goldblum R . Immunologic factors in human milk during the first year of lactation. J Pediatr 1982; 100: 563–567.

    Article  CAS  Google Scholar 

  6. Lönnerdal B . Human milk proteins: key components for the biological activity of human milk. Adv Exp Med Biol 2004; 554: 11–25.

    Article  Google Scholar 

  7. Vidal K, van den Broek P, Lorget F, Donnet-Hughes A . Osteoprotegerin in human milk: a potential role in the regulation of bone metabolism and immune development. Pediatr Res 2004; 55: 1001–1008.

    Article  CAS  Google Scholar 

  8. Ahima RS, Saper CB, Flier JS, Elmquist JK . Leptin regulation of neuroendocrine system. Front Neuroendocrinonol 2000; 21: 263–267.

    Article  CAS  Google Scholar 

  9. Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoetic cells. Proc Natl Acad Sci USA 1996; 93: 14564–14568.

    Article  CAS  Google Scholar 

  10. Bielicki J, Huch R, von Mandach U . Time-course of leptin levels in term and preterm human milk. Eur J Endocrinol 2004; 151: 271–276.

    Article  CAS  Google Scholar 

  11. Montagne P, Cuilliere ML, Mole C, Bene 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 

  12. Ballabio C, Bertino E, Coscia A, Fabris C, Fuggetta D, Molfino S et al. Immunoglobulin-A profile in breast milk from mothers delivering full term and preterm infants. Int J Immunopathol Pharmacol 2007; 20: 119–128.

    Article  CAS  Google Scholar 

  13. Velona T, Abbiati L, Beretta B, Gaiaschi A, Flauto U, Tagliabue P et al. Protein profiles in breast milk from mothers delivering term and preterm babies. Pediatr Res 1999; 45: 658–663.

    Article  CAS  Google Scholar 

  14. Koenig A, de Albuquerque Diniz EM, Barbosa SF, Vaz FA . Immunologic factors in human milk: the effects of gestational age and pasteurization. J Hum Lact 2005; 21: 439–443.

    Article  Google Scholar 

  15. Younes B, Al-Hakeem A, Al-Shammary F, Imambaccus Y . Breast milk lysozyme concentration in relation to age, period of lactation and parity of mothers. Med Sci Res 1994; 22: 323–324.

    CAS  Google Scholar 

  16. Schanler RJ, Hurst NM, Lau C . The use of human milk and breastfeeding in premature infants. Clin Perinatol 1999; 26: 379–398.

    Article  CAS  Google Scholar 

  17. McGuire W, Henderson G, Fowlie PW . Feeding the preterm infant. BMJ 2004; 329: 1227–1230.

    Article  Google Scholar 

  18. Goldman AS . Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J Nutr 2000; 130: 426S–431S.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  20. Doneray H, Orbak Z, Yildiz L . The relationship between breast milk leptin and neonatal weight gain. Acta Paediatr 2009; 98: 643–647.

    Article  CAS  Google Scholar 

  21. Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A . Antiinfective properties of human milk. J Nutr 2008; 138: 1801S–1806S.

    Article  CAS  Google Scholar 

  22. Deckers D, Vanlint D, Callewaert L, Aertsen A, Michiels CW . Role of the lysozyme inhibitor ivy in growth or survival of Escherichia coli and Pseudomonas aeruginosa bacteria in hen egg white and in human saliva and breast milk. Appl Environ Microbiol 2008; 74: 4434–4439.

    Article  CAS  Google Scholar 

  23. Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME . Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun 2004; 316: 924–929.

    Article  CAS  Google Scholar 

  24. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79–83.

    Article  CAS  Google Scholar 

  25. 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 

  26. Uçar B, Kirel B, Bör O, Kiliç FS, Doǧruel N, Aydoǧdu SD et al. Breast milk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. J Pediatr Endocrinol Metab 2000; 13: 149–156.

    Article  Google Scholar 

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We thank Nitin Goyal, Uday Nadgir and Zindadil Gandhi for running the ELISAs and EIAs. We also express our most sincere appreciation for the benevolent mothers for their participation and commitment to this research project.

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Correspondence to A Petrova.

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Mehta, R., Petrova, A. Biologically active breast milk proteins in association with very preterm delivery and stage of lactation. J Perinatol 31, 58–62 (2011).

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