Current Problems in Pediatric and Adolescent Health Care
Volume 37, Issue 1 , Pages 7-36 , January 2007

Human Breast Milk: Current Concepts of Immunology and Infectious Diseases

  • Robert M. Lawrence, MD

      Affiliations

    • University of Florida Department of Pediatrics, Division of Pediatric Immunology and Infectious Diseases, Gainesville, FL
    • Dr. Lawrence is co-author of a book on breastfeeding, Breastfeeding: A Guide for the Medical Profession, published by Elsevier Mosby.
    • ,
  • Camille A. Pane, MD

      Affiliations

    • University of Florida College of Public Health and Health Professions, Department of Public Health, Gainesville, FL.
    • Dr. Pane has no conflicts of interest.

References 

  1. Ryan AS, Wenjun Z, Acosta A. Breastfeeding continues to increase into the new millennium. Pediatrics. 2002;110(6):1103–1109
  2. Breastfeeding: Data and Statistics: Breastfeeding Practices—Results from the 2004 National Immunization Survey. 2004 [cited 2006 02/10/06]; Available from: http://www.cdc.gov/breastfeeding/data/NIS_data/data_2004.htm.
  3. Ross Products Division of Abbott. Mothers Survey, Ross Products Division of Abbott: 2004 Breastfeeding Trends. Columbus, OH; 2004.
  4. Healthy People 2010. 2000 [cited 2006 02/09/06]; Available from: http://www.healthypeople.gov/document/html/objectives/16-19.htm.
  5. American Academy of PediatricsWork Group on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 1997;100(6):1035–1039
  6. Breastfeeding: maternal and infant aspects. Washington, DC: American College of Obstetricians and Gynecologists; 2000;
  7. AAFP Policy Statement on Breastfeeding. Leawood, KS: American Academy of Family Physicians; 2001;
  8. Gartner LM, Morton J, Lawrence RA, Naylor AJ, O’Hare D, Schanler RJ, et al. Breastfeeding and the use of human milk. Pediatrics. 2005;115(2):496–506
  9. Whitsett JA. Surfactant proteins in innate host defense of the lung. Biol Neonate. 2005;88(3):175–180
  10. Newburg DS. Innate immunity and human milk. J Nutr. 2005;135(5):1308–1312
  11. Salminen SJ, Gueimonde M, Isolauri E. Probiotics that modify disease risk. J Nutr. 2005;135(5):1294–1298
  12. Isaacs CE. Human milk inactivates pathogens individually, additively, and synergistically. J Nutr. 2005;135(5):1286–1288
  13. Phadke SM, Deslouches B, Hileman SE, Montelaro RC, Wiesenfeld HC, Mietzner TA. Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection. J Nutr. 2005;135(5):1289–1293
  14. Morrow AL, Ruiz-Palacios GM, Jiang X, Newburg DS. Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea. J Nutr. 2005;135(5):1304–1307
  15. Christensen RD, MacFarlane JL, Taylor NL, Hill HR, Rothstein G. Blood and marrow neutrophils during experimental group B streptococcal infection: quantification of the stem cell, proliferative, storage and circulating pools. Pediatr Res. 1982;16(7):549–553
  16. Christensen RD, Shigeoka AO, Hill HR, Rothstein G. Circulating and storage neutrophil changes in experimental type II group B streptococcal sepsis. Pediatr Res. 1980;14(6):806–808
  17. Mease AD. Tissue neutropenia: the newborn neutrophil in perspective. J Perinatol. 1990;10(1):55–59
  18. Polin RA. Role of fibronectin in diseases of newborn infants and children. Rev Infect Dis. 1990;12(Suppl 4):S428–S438
  19. Schibler KR, Trautman MS, Liechty KW, White WL, Rothstein G, Christensen RD. Diminished transcription of interleukin-8 by monocytes from preterm neonates. J Leukoc Biol. 1993;53(4):399–403
  20. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA. 1987;84(24):9233–9237
  21. Yasui K, Masuda M, Tsuno T, Matsuoka T, Komiyama A, Akabane T, et al. An increase in polymorphonuclear leucocyte chemotaxis accompanied by a change in the membrane fluidity with age during childhood. Clin Exp Immunol. 1990;81(1):156–159
  22. Wolach B, Ben Dor M, Chomsky O, Gavrieli R, Shinitzky M. Improved chemotactic ability of neonatal polymorphonuclear cells induced by mild membrane rigidification. J Leukoc Biol. 1992;51(4):324–328
  23. Hilmo A, Howard TH. F-actin content of neonate and adult neutrophils. Blood. 1987;69(3):945–949
  24. Buhrer C, Graulich J, Stibenz D, Dudenhausen JW, Obladen M. L-selectin is down-regulated in umbilical cord blood granulocytes and monocytes of newborn infants with acute bacterial infection. Pediatr Res. 1994;36(6):799–804
  25. McCracken GH, Eichenwald HF. Leukocyte function and the development of opsonic and complement activity in the neonate. Am J Dis Child. 1971;121(2):120–126
  26. Strauss RG, Snyder EL. Activation and activity of the superoxide-generating system of neutrophils from human infants. Pediatr Res. 1983;17(8):662–664
  27. Shigeoka AO, Santos JI, Hill HR. Functional analysis of neutrophil granulocytes from healthy, infected, and stressed neonates. J Pediatr. 1979;95(3):454–460
  28. Levy O, Martin S, Eichenwald E, Ganz T, Valore E, Carroll SF, et al. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics. 1999;104(6):1327–1333
  29. Satwani P, Morris E, van de Ven C, Cairo MS. Dysregulation of expression of immunoregulatory and cytokine genes and its association with the immaturity in neonatal phagocytic and cellular immunity. Biol Neonate. 2005;88(3):214–227
  30. Gillan ER, Christensen RD, Suen Y, Ellis R, van de Ven C, Cairo MS. A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood. 1994;84(5):1427–1433
  31. Bernstein HM, Pollock BH, Calhoun DA, Christensen RD. Administration of recombinant granulocyte colony-stimulating factor to neonates with septicemia: a meta-analysis. J Pediatr. 2001;138(6):917–920
  32. Carr R, Modi N, Dore C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev. 2003;(3):CD003066
  33. Hannet I, Erkeller-Yuksel F, Lydyard P, Deneys V, DeBruyere M. Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today. 1992;13(6):215;8
  34. Stites DP, Carr MC, Fudenberg HH. Ontogeny of cellular immunity in the human fetus: development of responses to phytohemagglutinin and to allogeneic cells. Cell Immunol. 1974;11(1-3):257–271
  35. Splawski JB, Jelinek DF, Lipsky PE. Delineation of the functional capacity of human neonatal lymphocytes. J Clin Invest. 1991;87(2):545–553
  36. Clement LT, Vink PE, Bradley GE. Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J Immunol. 1990;145(1):102–108
  37. Wilson CB, Lewis DB. Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infect Dis. 1990;12(Suppl 4):S410–S420
  38. Lewis DB, Yu CC, Meyer J, English BK, Kahn SJ, Wilson CB. Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells. J Clin Invest. 1991;87(1):194–202
  39. Kilpinen S, Hurme M. Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells. Immunology. 1998;94(2):167–172
  40. English BK, Hammond WP, Lewis DB, Brown CB, Wilson CB. Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells. Pediatr Res. 1992;31(3):211–216
  41. Palacios R, Andersson U. Autologous mixes lymphocyte reaction in human cord blood lymphocytes: decreased generation of helper and cytotoxic T-cell functions and increased proliferative response and induction of suppressor T cells. Cell Immunol. 1982;66(1):88–98
  42. Phillips JH, Hori T, Nagler A, Bhat N, Spits H, Lanier LL. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon, delta proteins. J Exp Med. 1992;175(4):1055–1066
  43. Nair MP, Schwartz SA, Menon M. Association of decreased natural and antibody-dependent cellular cytotoxicity and production of natural killer cytotoxic factor and interferon in neonates. Cell Immunol. 1985;94(1):159–171
  44. Yabuhara A, Kawai H, Komiyama A. Development of natural killer cytotoxicity during childhood: marked increases in number of natural killer cells with adequate cytotoxic abilities during infancy to early childhood. Pediatr Res. 1990;28(4):316–322
  45. Kohl S. The neonatal human’s immune response to herpes simplex virus infection: a critical review. Pediatr Infect Dis J. 1989;8(2):67–74
  46. Kohl S. Role of antibody-dependent cellular cytotoxicity in defense against herpes simplex virus infections. Rev Infect Dis. 1991;13(1):108–114
  47. Shore SL, Milgrom H, Wood PA, Nahmias AJ. Antibody-dependent cellular cytotoxicity to target cells infected with herpes simplex viruses: functional adequacy in the neonate. Pediatrics. 1977;59(1):22–28
  48. Merrill JD, Sigaroudinia M, Kohl S. Characterization of natural killer and antibody-dependent cellular cytotoxicity of preterm infants against human immunodeficiency virus-infected cells. Pediatr Res. 1996;40(3):498–503
  49. Morell A, Skvaril F, Hitzig WH, Barandun S. IgG subclasses: development of the serum concentrations in “normal” infants and children. J Pediatr. 1972;80(6):960–964
  50. Einhorn MS, Granoff DM, Nahm MH, Quinn A, Shackelford PG. Concentrations of antibodies in paired maternal and infant sera: relationship to IgG subclass. J Pediatr. 1987;111(5):783–788
  51. Kohler PF, Farr RS. Elevation of cord over maternal IgG immunoglobulin: evidence for an active placental IgG transport. Nature. 1966;210(40):1070–1071
  52. Ballow M, Cates KL, Rowe JC, Goetz C, Desbonnet C. Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res. 1986;20(9):899–904
  53. Stiehm ER, Fudenberg HH. Serum levels of immune globulins in health and disease: a survey. Pediatrics. 1966;37(5):715–727
  54. Ferrieri P. Neonatal susceptibility and immunity to major bacterial pathogens. Rev Infect Dis. 1990;12(Suppl 4):S394–S400
  55. Dossett JH, Williams RC, Quie PG. Studies on interaction of bacteria, serum factors and polymorphonuclear leukocytes in mothers and newborns. Pediatrics. 1969;44(1):49–57
  56. Cooper MD. Current concepts. B lymphocytes. Normal development and function. N Engl J Med. 1987;317(23):1452–1456
  57. Hayward AR, Lydyard PM. B cell function in the newborn. Pediatrics. 1979;64(5 Pt. 2 Suppl):758–764
  58. Ben-Hur H, Gurevich P, Huszar M, Ziv-Sokolovsky N, Zion H, Isaegson I, et al. Immunoglobulin A in the epithelium of the respiratory tract and intrahepatic bile ducts of fetuses and newborns with pneumonia and sepsis. Hum Antibodies. 1997;8(3):119–123
  59. Bernbaum JC, Daft A, Anolik R, Samuelson J, Barkin R, Douglas S, et al. Response of preterm infants to diphtheria-tetanus-pertussis immunizations. J Pediatr. 1985;107(2):184–188
  60. Dengrove J, Lee EJ, Heiner DC, St Geme JW, Leake R, Baraff LJ, et al. IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization. Pediatr Res. 1986;20(8):735–739
  61. Smolen P, Bland R, Heiligenstein E, Lawless MR, Dillard R, Abramson J. Antibody response to oral polio vaccine in premature infants. J Pediatr. 1983;103(6):917–919
  62. Smith RT, Eitzman DV. The development of the immune response (Characterization of the response of the human infant and adult to immunization with Salmonella Vaccines). Pediatrics. 1964;33:163–183
  63. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev. 2004;(1):CD001239
  64. Sonntag J, Brandenburg U, Polzehl D, Strauss E, Vogel M, Dudenhausen JW, et al. Complement system in healthy term newborns: reference values in umbilical cord blood. Pediatr Dev Pathol. 1998;1(2):131–135
  65. Wolach B, Dolfin T, Regev R, Gilboa S, Schlesinger M. The development of the complement system after 28 weeks’ gestation. Acta Paediatr. 1997;86(5):523–527
  66. Adamkin D, Stitzel A, Urmson J, Farnett ML, Post E, Spitzer R. Activity of the alternative pathway of complement in the newborn infant. J Pediatr. 1978;93(4):604–608
  67. Edwards MS, Buffone GJ, Fuselier PA, Weeks JL, Baker CJ. Deficient classical complement pathway activity in newborn sera. Pediatr Res. 1983;17(8):685–688
  68. Anderson DC, Hughes BJ, Edwards MS, Buffone GJ, Baker CJ. Impaired chemotaxigenesis by type III group B streptococci in neonatal sera: relationship to diminished concentration of specific anticapsular antibody and abnormalities of serum complement. Pediatr Res. 1983;17(6):496–502
  69. Lassiter HA, Wilson JL, Feldhoff RC, Hoffpauir JM, Klueber KM. Supplemental complement component C9 enhances the capacity of neonatal serum to kill multiple isolates of pathogenic Escherichia coli. Pediatr Res. 1994;35(4 Pt. 1):389–396
  70. Brandtzaeg PE. Current understanding of gastrointestinal immunoregulation and its relation to food allergy. Ann NY Acad Sci. 2002;964:13–45
  71. Polak-Charcon S, Shoham J, Ben-Shaul Y. Tight junctions in epithelial cells of human fetal hindgut, normal colon, and colon adenocarcinoma. J Natl Cancer Inst. 1980;65(1):53–62
  72. Buisine MP, Devisme L, Degand P, Dieu MC, Gosselin B, Copin MC, et al. Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands (II. Duodenum and liver, gallbladder, and pancreas). J Histochem Cytochem. 2000;48(12):1667–1676
  73. Muller CA, Autenrieth IB, Peschel A. Innate defenses of the intestinal epithelial barrier. Cell Mol Life Sci. 2005;62(12):1297–1307
  74. Picker LJ, Treer JR, Ferguson-Darnell B, Collins PA, Bergstresser PR, Terstappen LW. Control of lymphocyte recirculation in man (II. Differential regulation of the cutaneous lymphocyte-associated antigen, a tissue-selective homing receptor for skin-homing T cells). J Immunol. 1993;150(3):1122–1136
  75. Brandtzaeg P, Farstad IN, Johansen FE, Morton HC, Norderhaug IN, Yamanaka T. The B-cell system of human mucosae and exocrine glands. Immunol Rev. 1999;171:45–87
  76. Goldman AS. The immune system of human milk: antimicrobial, antiinflammatory and immunomodulating properties. Pediatr Infect Dis J. 1993;12(8):664–671
  77. Heinig MJ. Host defense benefits of breastfeeding for the infant (Effect of breastfeeding duration and exclusivity). Pediatr Clin North Am. 2001;48(1):105–123ix
  78. Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS. Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am. 1991;20(3):397–439
  79. Stoll BJ, Lee FK, Hale E, Schwartz D, Holmes R, Ashby R, et al. Immunoglobulin secretion by the normal and the infected newborn infant. J Pediatr. 1993;122(5 Pt. 1):780–786
  80. Haneberg B. Immunoglobulins in feces from infants fed human or bovine milk. Scand J Immunol. 1974;3(2):191–197
  81. Brandtzaeg P. The secretory immune system of lactating human mammary glands compared with other exocrine organs. Ann NY Acad Sci. 1983;409:353–382
  82. Giugliano LG, Ribeiro ST, Vainstein MH, Ulhoa CJ. Free secretory component and lactoferrin of human milk inhibit the adhesion of enterotoxigenic Escherichia coli. J Med Microbiol. 1995;42(1):3–9
  83. Hammerschmidt S, Talay SR, Brandtzaeg P, Chhatwal GS. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol Microbiol. 1997;25(6):1113–1124
  84. Dallas SD, Rolfe RD. Binding of Clostridium difficile toxin A to human milk secretory component. J Med Microbiol. 1998;47(10):879–888
  85. Hamosh M. Bioactive factors in human milk. Pediatr Clin North Am. 2001;48(1):69–86
  86. Sanchez L, Calvo M, Brock JH. Biological role of lactoferrin. Arch Dis Child. 1992;67(5):657–661
  87. Tomita M, Takase M, Wakabayashi H, Bellamy W. Antimicrobial peptides of lactoferrin. Adv Exp Med Biol. 1994;357:209–218
  88. Cleary TG, Hyani K, Winsor DK, Ruiz-Palacios G. Milk secretory IgA related to Shigella virulence antigens. Adv Exp Med Biol. 1991;310:369–373
  89. Hamosh M. Protective function of proteins and lipids in human milk. Biol Neonate. 1998;74(2):163–176
  90. Newburg DS. Oligosaccharides and glyconjugates in human milk: their role in host defense. J Mammary Gland Biol Neoplasia. 1996;1(3):271–283
  91. Peterson JA, Patton S, Hamosh M. Glycoproteins of the human milk fat globule in the protection of the breast-fed infant against infections. Biol Neonate. 1998;74(2):143–162
  92. Hamosh M, Peterson JA, Henderson TR, Scallan CD, Kiwan R, Ceriani RL, et al. Protective function of human milk: the milk fat globule. Semin Perinatol. 1999;23(3):242–249
  93. Garofalo RP, Goldman AS. Expression of functional immunomodulatory and anti-inflammatory factors in human milk. Clin Perinatol. 1999;26(2):361–377
  94. Donovan SM, Odle J. Growth factors in milk as mediators of infant development. Annu Rev Nutr. 1994;14:147–167
  95. Labeta MO, Vidal K, Nores JE, Arias M, Vita N, Morgan BP, et al. Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14. J Exp Med. 2000;191(10):1807–1812
  96. LeBouder E, Rey-Nores JE, Rushmere NK, Grigorov M, Lawn SD, Affolter M, et al. Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol. 2003;171(12):6680–6689
  97. Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defense. Br J Nutr. 2005;93(Suppl 1):S41–S48
  98. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291(5505):881–884
  99. Mountzouris KC, McCartney AL, Gibson GR. Intestinal microflora of human infants and current trends for its nutritional modulation. Br J Nutr 20027(5):405-20.
  100. Sghir A, Chow JM, Mackie RI. Continuous culture selection of bifidobacteria and lactobacilli from human faecal samples using fructooligosaccharide as selective substrate. J Appl Microbiol. 1998;85(4):769–777
  101. Dai D, Nanthkumar NN, Newburg DS, Walker WA. Role of oligosaccharides and glycoconjugates in intestinal host defense. J Pediatr Gastroenterol Nutr. 2000;30(Suppl 2):S23–S33
  102. Roller M, Rechkemmer G, Watzl B. Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats. J Nutr. 2004;134(1):153–156
  103. Fanaro S, Chierici R, Guerrini P, Vigi V. Intestinal microflora in early infancy: composition and development. Acta Paediatr Suppl. 2003;91(441):48–55
  104. Glass RI, Svennerholm AM, Stoll BJ, Khan MR, Hossain KM, Huq MI, et al. Protection against cholera in breast-fed children by antibodies in breast milk. N Engl J Med. 1983;308(23):1389–1392
  105. Hoy C, Millar MR, MacKay P, Godwin PG, Langdale V, Levene MI. Quantitative changes in faecal microflora preceding necrotising enterocolitis in premature neonates. Arch Dis Child. 1990;65(10 Spec No):1057–1059
  106. Millar MR, MacKay P, Levene M, Langdale V, Martin C. Enterobacteriaceae and neonatal necrotising enterocolitis. Arch Dis Child. 1992;67(1 Spec No):53–56
  107. Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS, Panigrahi P. Stool microflora in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1999;80(3):F167–F173
  108. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005;147(2):192–196
  109. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis. 1999;3(4):197–202
  110. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2005;115(1):1–4
  111. Luig M, Lui K. Epidemiology of necrotizing enterocolitis—Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41(4):174–179
  112. Euler AR, Mitchell DK, Kline R, Pickering LK. Prebiotic effect of fructo-oligosaccharide supplemented term infant formula at two concentrations compared with unsupplemented formula and human milk. J Pediatr Gastroenterol Nutr. 2005;40(2):157–164
  113. Rinne M, Kalliomaki M, Arvilommi H, Salminen S, Isolauri E. Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses. J Pediatr. 2005;147(2):186–191
  114. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants (A prospective double-blind study). Biol Neonate. 2002;82(2):103–108
  115. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322(7298):1327
  116. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the Medical Profession. 6th Edition. Philadelphia (PA): Elsevier Mosby; 2005;
  117. Gustafsson L, Hallgren O, Mossberg AK, Pettersson J, Fischer W, Aronsson A, et al. HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy. J Nutr. 2005;135(5):1299–1303
  118. Carver JD. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr Suppl. 1999;88(430):83–88
  119. Leach JL, Baxter JH, Molitor BE, Ramstack MB, Masor ML. Total potentially available nucleosides of human milk by stage of lactation. Am J Clin Nutr. 1995;61(6):1224–1230
  120. Tressler RL, Ramstack MB, White NR, Molitor BE, Chen NR, Alarcon P, et al. Determination of total potentially available nucleosides in human milk from Asian women. Nutrition. 2003;19(1):16–20
  121. Brunser O, Espinoza J, Araya M, Cruchet S, Gil A. Effect of dietary nucleotide supplementation on diarrhoeal disease in infants. Acta Paediatr. 1994;83(2):188–191
  122. Navarro J, Maldonado J, Narbona E, Ruiz-Bravo A, Garcia Salmeron JL, Molina JA, et al. Influence of dietary nucleotides on plasma immunoglobulin levels and lymphocyte subsets of preterm infants. Biofactors. 1999;10(1):67–76
  123. Pickering LK, Granoff DM, Erickson JR, Masor ML, Cordle CT, Schaller JP, et al. Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics. 1998;101(2):242–249
  124. Garofalo RP, Goldman AS. Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update. Biol Neonate. 1998;74(2):134–142
  125. Murakami M, Dorschner RA, Stern LJ, Lin KH, Gallo RL. Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk. Pediatr Res. 2005;57(1):10–15
  126. Dinarello CA, Wolff SM. The role of interleukin-1 in disease. N Engl J Med. 1993;328(2):106–113
  127. Hale KK, Smith CG, Baker SL, Vanderslice RW, Squires CH, Gleason TM, et al. Multifunctional regulation of the biological effects of TNF-alpha by the soluble type I and type II TNF receptors. Cytokine. 1995;7(1):26–38
  128. Murphey DK, Buescher ES. Human colostrum has anti-inflammatory activity in a rat subcutaneous air pouch model of inflammation. Pediatr Res. 1993;34(2):208–212
  129. Lindberg T, Ohlsson K, Westrom B. Protease inhibitors and their relation to protease activity in human milk. Pediatr Res. 1982;16(6):479–483
  130. Ostrea EM, Balun JE, Winkler R, Porter T. Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and beta-carotene in the newborn infant. Am J Obstet Gynecol. 1986;154(5):1014–1017
  131. Smolen JE, Korchak HM, Weissmann G. The roles of extracellular and intracellular calcium in lysosomal enzyme release and superoxide anion generation by human neutrophils. Biochim Biophys Acta. 1981;677(3-4):512–520
  132. Caplan M, Hsueh W, Kelly A, Donovan M. Serum PAF acetylhydrolase increases during neonatal maturation. Prostaglandins. 1990;39(6):705–714
  133. Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalstieg FC, et al. Interleukin-10 in human milk. Pediatr Res. 1995;37(4 Pt. 1):444–449
  134. Chantry D, Turner M, Abney E, Feldmann M. Modulation of cytokine production by transforming growth factor-beta. J Immunol. 1989;142(12):4295–4300
  135. Wagner CL, Anderson DM, Pittard WB. Special properties of human milk. Clin Pediatr (Phila). 1996;35(6):283–293
  136. Walker WA. The dynamic effects of breastfeeding on intestinal development and host defense. Adv Exp Med Biol. 2004;554:155–170
  137. Lau C. Effects of stress on lactation. Pediatr Clin North Am. 2001;48(1):221–234
  138. Picciano MF. Nutrient composition of human milk. Pediatr Clin North Am. 2001;48(1):53–67
  139. Jensen RG. Handbook of Milk Composition. San Diego (CA): Academic Press; 1995;
  140. Hibberd CM, Brooke OG, Carter ND, Haug M, Harzer G. Variation in the composition of breast milk during the first 5 weeks of lactation: implications for the feeding of preterm infants. Arch Dis Child. 1982;57(9):658–662
  141. Beisel WR. Nutrient Requirements in Adolescence. Cambridge (MA): MIT Press; 1976;
  142. Hoyle B, Yunus M, Chen LC. Breast-feeding and food intake among children with acute diarrheal disease. Am J Clin Nutr. 1980;33(11):2365–2371
  143. Sachdev HP, Krishna J, Puri RK. Do exclusively breast fed infants need fluid supplementation?. Indian Pediatr. 1992;29(4):535–540
  144. Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-cell response. Nat Rev Immunol. 2005;5(11):844–852
  145. Siciliano R, Rega B, Marchetti M, Seganti L, Antonini G, Valenti P. Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection. Biochem Biophys Res Commun. 1999;264(1):19–23
  146. Lawrence RM, Lawrence RA. Breast milk and infection. Clin Perinatol. 2004;31(3):501–528
  147. Labbok M, Krasovec K. Toward consistency in breastfeeding definitions. Stud Fam Plann. 1990;21(4):226–230
  148. DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children’s health. Pediatrics. 2004;113(Suppl 4):1007–1015
  149. Kramer MS, Kakuma R. The optimal duration of exclusive breastfeeding: a systematic review. Adv Exp Med Biol. 2004;554:63–77
  150. Martin JA, Kochanek KD, Strobino DM, Guyer B, MacDorman MF. Annual summary of vital statistics—2003. Pediatrics. 2005;115(3):619–634
  151. Chen A, Rogan WJ. Breastfeeding and the risk of postneonatal death in the United States. Pediatrics. 2004;113(5):e435–e439
  152. Bahl R, Frost C, Kirkwood BR, Edmond K, Martines J, Bhandari N, et al. Infant feeding patterns and risks of death and hospitalization in the first half of infancy: multicentre cohort study. Bull World Health Organ. 2005;83(6):418–426
  153. Arifeen S, Black RE, Antelman G, Baqui A, Caulfield L, Becker S. Exclusive breastfeeding reduces acute respiratory infection and diarrhea deaths among infants in Dhaka slums. Pediatrics. 2001;108(4):E67
  154. Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year?. Lancet. 2003;361(9376):2226–2234
  155. Morrow AL, Rangel JM. Human milk protection against infectious diarrhea: implications for prevention and clinical care. Semin Pediatr Infect Dis. 2004;15(4):221–228
  156. Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk glycans protect infants against enteric pathogens. Annu Rev Nutr. 2005;25:37–58
  157. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States. Pediatrics. 1997;99(6):E5
  158. Dewey KG, Heinig MJ, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants. J Pediatr. 1995;126(5 Pt 1):696–702
  159. Beaudry M, Dufour R, Marcoux S. Relation between infant feeding and infections during the first six months of life. J Pediatr. 1995;126(2):191–197
  160. Kramer MS, Chalmers B, Hodnett ED, Sevkovskaya Z, Dzikovich I, Shapiro S, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA. 2001;285(4):413–420
  161. Kramer MS, Guo T, Platt RW, Sevkovskaya Z, Dzikovich I, Collet JP, et al. Infant growth and health outcomes associated with 3 compared with 6 mo of exclusive breastfeeding. Am J Clin Nutr. 2003;78(2):291–295
  162. Duffy LC, Byers TE, Riepenhoff-Talty M, La Scolea LJ, Zielezny M, Ogra PL. The effects of infant feeding on rotavirus-induced gastroenteritis: a prospective study. Am J Public Health. 1986;76(3):259–263
  163. Duffy LC, Riepenhoff-Talty M, Byers TE, La Scolea LJ, Zielezny MA, Dryja DM, et al. Modulation of rotavirus enteritis during breast-feeding (Implications on alterations in the intestinal bacterial flora). Am J Dis Child. 1986;140(11):1164–1168
  164. Clemens JD, Rao MR, Chakraborty J, Yunus M, Ali M, Kay B, et al. Breastfeeding and the risk of life-threatening enterotoxigenic Escherichia coli diarrhea in Bangladeshi infants and children. Pediatrics. 1997;100(6):E2
  165. Walterspiel JN, Morrow AL, Guerrero ML, Ruiz-Palacios GM, Pickering LK. Secretory anti-Giardia lamblia antibodies in human milk: protective effect against diarrhea. Pediatrics. 1994;93(1):28–31
  166. Ruiz-Palacios GM, Calva JJ, Pickering LK, Lopez-Vidal Y, Volkow P, Pezzarossi H, et al. Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk. J Pediatr. 1990;116(5):707–713
  167. Morrow AL, Reves RR, West MS, Guerrero ML, Ruiz-Palacios GM, Pickering LK. Protection against infection with Giardia lamblia by breast-feeding in a cohort of Mexican infants. J Pediatr. 1992;121(3):363–370
  168. Tellez A, Winiecka-Krusnell J, Paniagua M, Linder E. Antibodies in mother’s milk protect children against giardiasis. Scand J Infect Dis. 2003;35(5):322–325
  169. Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: a meta-analysis. Arch Pediatr Adolesc Med. 2003;157(3):237–243
  170. Cesar JA, Victora CG, Barros FC, Santos IS, Flores JA. Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested case-control study. BMJ. 1999;318(7194):1316–1320
  171. Sinha A, Madden J, Ross-Degnan D, Soumerai S, Platt R. Reduced risk of neonatal respiratory infections among breastfed girls but not boys. Pediatrics. 2003;112(4):e303
  172. Pettigrew MM, Khodaee M, Gillespie B, Schwartz K, Bobo JK, Foxman B. Duration of breastfeeding, daycare, and physician visits among infants 6 months and younger. Ann Epidemiol. 2003;13(6):431–435
  173. Duffy LC, Faden H, Wasielewski R, Wolf J, Krystofik D. Exclusive breastfeeding protects against bacterial colonization and day care exposure to otitis media. Pediatrics. 1997;100(4):E7
  174. Duncan B, Ey J, Holberg CJ, Wright AL, Martinez FD, Taussig LM. Exclusive breast-feeding for at least 4 months protects against otitis media. Pediatrics. 1993;91(5):867–872
  175. Aniansson G, Alm B, Andersson B, Hakansson A, Larsson P, Nylen O, et al. A prospective cohort study on breast-feeding and otitis media in Swedish infants. Pediatr Infect Dis J. 1994;13(3):183–188
  176. Hanson LA. Protective effects of breastfeeding against urinary tract infection. Acta Paediatr. 2004;93(2):154–156
  177. Marild S, Hansson S, Jodal U, Oden A, Svedberg K. Protective effect of breastfeeding against urinary tract infection. Acta Paediatr. 2004;93(2):164–168
  178. Pisacane A, Graziano L, Mazzarella G, Scarpellino B, Zona G. Breast-feeding and urinary tract infection. J Pediatr. 1992;120(1):87–89
  179. Diehl-Jones WL, Askin DF. Nutritional modulation of neonatal outcomes. AACN Clin Issues. 2004;15(1):83–96
  180. McGuire W, Anthony MY. Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review. Arch Dis Child Fetal Neonatal Ed. 2003;88(1):F11–F14
  181. Schanler RJ, Shulman RJ, Lau C. Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula. Pediatrics. 1999;103(6 Pt 1):1150–1157
  182. Hylander MA, Strobino DM, Dhanireddy R. Human milk feedings and infection among very low birth weight infants. Pediatrics. 1998;102(3):E38
  183. el-Mohandes AE, Picard MB, Simmens SJ, Keiser JF. Use of human milk in the intensive care nursery decreases the incidence of nosocomial sepsis. J Perinatol. 1997;17(2):130–134
  184. O’Connor DL, Jacobs J, Hall R, Adamkin D, Auestad N, Castillo M, et al. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula. J Pediatr Gastroenterol Nutr. 2003;37(4):437–446
  185. Schanler RJ, Lau C, Hurst NM, Smith EO. Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics. 2005;116(2):400–406
  186. Blaymore Bier JA, Oliver T, Ferguson A, Vohr BR. Human milk reduces outpatient upper respiratory symptoms in premature infants during their first year of life. J Perinatol. 2002;22(5):354–359
  187. Raisler J, Alexander C, O’Campo P. Breast-feeding and infant illness: a dose-response relationship?. Am J Public Health. 1999;89(1):25–30
  188. 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(1):66–71

 Neither author has funding sources that contributed to the writing of this manuscript.

PII: S1538-5442(06)00107-6

doi: 10.1016/j.cppeds.2006.10.002

Current Problems in Pediatric and Adolescent Health Care
Volume 37, Issue 1 , Pages 7-36 , January 2007

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