Clinical Reviews in Allergy & Immunology

, Volume 34, Issue 2, pp 191–204 | Cite as

Host Factors in Amniotic Fluid and Breast Milk that Contribute to Gut Maturation

  • Carol L. Wagner
  • Sarah N. Taylor
  • Donna Johnson


The gut represents a complex organ system with regional differences, which reflect selective digestive and absorptive functions that change constantly in response to bodily requirements and the outside milieu. As a barrier to the external environment, gut epithelium must be renewed rapidly and repeatedly. Growth and renewal of gut epithelial cells is dependent on controlled cell stimulation and proliferation by a number of signaling processes and agents, including gut peptides—both endogenous and exogenous sources. This cascade of events begins during fetal development; with the ingestion of amniotic fluid, this process is enhanced and continued during infancy and early childhood through the ingestion of human milk. Events influenced by amniotic fluid during fetal development and those influenced by human milk that unfold after birth and early childhood to render the gut mature are presented.


Amniotic fluid Breast milk Gut Maturation 


  1. 1.
    Neu J, Li N (2003) The neonatal gastrointestinal tract: developmental anatomy, physiology, and clinical implications. Neoreviews e4:7–13Google Scholar
  2. 2.
    Shah U, Sanderson I (1999) Role of the intestinal lumen in the ontogeny of the gastrointestinal tract. In: Sanderson I, Walker W (eds) Development of the gastrointestinal tract. B.C. Decker, Hamilton, CanadaGoogle Scholar
  3. 3.
    Weaver L, Walker WA (1988) Epidermal growth factor and the developing human gut. Gastroenterology 94:845–847PubMedGoogle Scholar
  4. 4.
    Blakelock R, Upadhyay V, Kimble R, Pease P, Kolbe A, Harding J (1998) Is a normally functioning gastrointestinal tract necessary for normal growth in late gestation? Pediatr Surg Int 13:17–20PubMedGoogle Scholar
  5. 5.
    Dupont C, Goutail-Flaud MF (1990) Alterations of intestinal permeability to sugars in infants following neonatal surgery. J Pediatr Gastroenterol Nutr 11:66–71PubMedGoogle Scholar
  6. 6.
    Khen N, Jaubert F, Sauvat F, Fourcade L, Jan D, Martinovic J, Vekemans M, Landais P, Brousse N, Leborgne M et al (2004) Fetal intestinal obstruction induces alteration of enteric nervous system development in human intestinal atresia. Pediatr Res 56:975–980PubMedGoogle Scholar
  7. 7.
    Condino A, Barleycorn A, Lu W, Maheshwari A, Christensen R, Calhoun D (2004) Abnormal intestinal histology in neonates with congenital anomalies of the gastrointestinal tract. Biol Neonate 85:145–150PubMedGoogle Scholar
  8. 8.
    Trahair J, Harding R, Bocking A, Silver M, Robinson P (1986) The role of ingestion in the development of the small intestine in fetal sheep. Q J Exp Physiol 71:99–104PubMedGoogle Scholar
  9. 9.
    Trahair JF, Harding R (1995) Restitution of swallowing in the fetal sheep restores intestinal growth after midgestation esophageal obstruction. J Pediatr Gastroenterol Nutr 20:156–161PubMedGoogle Scholar
  10. 10.
    Trahair J, Sangild P (2000) Fetal organ growth in response to oesophageal infusion of amniotic fluid, colostrum, milk or gastrin-releasing peptide: a study in fetal sheep. Reprod Fertil Dev 12:87–95PubMedGoogle Scholar
  11. 11.
    Godlewski M, Slupecka M, Wolinske J, Skrzypek T, Skrzypek H, Motyl T, Zabielski R (2005) Into the unknown–The death pathways in the neonatal gut epithelium. J Physiol Pharmacol 56:7–24PubMedGoogle Scholar
  12. 12.
    Hamosh M (1996) Digestion in the newborn. Clin Perinatology 23:191–209Google Scholar
  13. 13.
    Maheshwari A (2004) Role of cytokines in human intestinal villous development. Clinics Perinatology 31:1–11Google Scholar
  14. 14.
    Brandtzaeg P (2002) The secretory immunoglobulin system: Regulation and biological significance. In: Davis M, Isaacs C (eds) Integrating population outcomes, biological mechanisms and research methods in the study of human milk and lactation. Plenum, New York, pp 1–16Google Scholar
  15. 15.
    van Odijk J, Kull I, Borres MP, Brandtzaeg P, Edberg U, Hanson LA, Host A, Kuitunen M, Olsen SF, Skerfving S et al (2003) Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy 58:833–843PubMedGoogle Scholar
  16. 16.
    Sherman P, Forstner J, Roomi N, Khatri I, Forstner G (1985) Mucin depletion in the intestine of malnourished rats. Am J Physiol 284:G418–G423Google Scholar
  17. 17.
    Underwood MA, Sherman MP (2006) Nutritional characteristics of amniotic fluid. Neoreviews 7:e310–e316Google Scholar
  18. 18.
    Brace R (1997) Physiology of amniotic fluid volume regulation. Clin Obstet Gynecol 40:280–289PubMedGoogle Scholar
  19. 19.
    Mulvihill SJ, Stone MM, Debas HT, Fonkalsrud EW (1985) The role of amniotic fluid in fetal nutrition. J Pediatr Surg 20:668–672PubMedGoogle Scholar
  20. 20.
    Pitkin R, Reynolds W (1975) Fetal ingestion and metabolism of amniotic fluid protein. Am J Obstet Gynecol 123:356–363PubMedGoogle Scholar
  21. 21.
    Mandelbaum B, Evans T (1969) Life in the amniotic fluid. Am J Obstet Gynecol 104:365–377PubMedGoogle Scholar
  22. 22.
    Chochinov R, Ketupanya A, Mariz I, Underwood L, Daughaday W (1976) Amniotic fluid reactivity detected by somatomedin C radioreceptor assay: correlation with growth hormone, prolactin, and fetal renal maturation. J Clin Endocrinal Metab 42:983–986Google Scholar
  23. 23.
    Barka T, Van der Noen H, Gresik E, Kerenyi T (1978) Immunoreactive epidermal growth factor in human amniotic fluid. Mt Sinai J Med 45:679–684PubMedGoogle Scholar
  24. 24.
    Mulvihill SJ, Hallden G, Debas HT (1989) Trophic effect of amniotic fluid on cultured fetal gastric mucosal cells. J Surg Res 1989:327–329Google Scholar
  25. 25.
    Merimee T, Grant M, Tyson J (1984) Insulin-like growth factors in amniotic fluid. J Clin Endocrinal Metab 59:752–755Google Scholar
  26. 26.
    Maheshwari A, Lu W, Lacson A, Barleycorn AA, Nolan S, Christensen RD, Calhoun DA (2002) Effects of interleukin-8 on the developing human intestine. Cytokine 20:256–267PubMedGoogle Scholar
  27. 27.
    Koldovsky O, Britton J, Grimes J (1991) Milk-borne epidermal growth factor (EGF) and its processing in developing gastrointestinal tract. Endocrine Regulations 25:58–62PubMedGoogle Scholar
  28. 28.
    Playford R (1995) Peptides and gastrointestinal mucosal integrity. Gut 37:595–597PubMedGoogle Scholar
  29. 29.
    Seare N, Playford R (1998) Growth factors and gut function. Proc Nutr Soc 57:403–408PubMedGoogle Scholar
  30. 30.
    Opleta-Madsen K, Hardin J, Gall D (1991) Epidermal growth factor upregulates intestinal electrolytes and nutrient transport. Am J Physiol 260:G807–G814PubMedGoogle Scholar
  31. 31.
    Bines J, Walker W (1991) Growth factors and the development of neonatal host defense. In: Mestecky J, Blair C, Ogra P (eds) Advances in experimental medicine and biology, immunology of milk and the neonate. Plenum, New York, NY, pp 31–39Google Scholar
  32. 32.
    Murphy M (1998) Growth factors and the gastrointestinal tract. Nutrition 14:771–774PubMedGoogle Scholar
  33. 33.
    Mulvihill SJ, Stone MM, Fonkalsrud EW, Debas HT (1986) Trophic effect of amniotic fluid on fetal gastrointestinal development. J Surg Res 40:291–296PubMedGoogle Scholar
  34. 34.
    D'Ercole A, Drop S, Kortleve D (1985) Somatomedin-C/insulin-like growth factor I-binding proteins in human amniotic fluid and in fetal and postnatal blood: evidence of immunological homology. J Clin Endocrinal Metab 61:612–617CrossRefGoogle Scholar
  35. 35.
    Suik A-M (1989) Insulin-like growth factor (IGF-1) and its low molecular weight binding protein in human milk. Eur J Obstet Gynecol Reprod Biol 30:19–25Google Scholar
  36. 36.
    Hirai C, Ichiba H, Saito M, Shintaku H, Yamano T, Kusuda S (2002) Trophic effect of multiple growth factors in amniotic fluid or human milk on cultured human fetal small intestinal cells. J Pediatr Gastroenterol Nutr 34:524–528PubMedGoogle Scholar
  37. 37.
    Wagner CL, Forsythe DW (2000) Effect of human milk and recombinant EGF, TGFalpha, and IGF-1 on small intestinal cell proliferation. Adv Exp Med Biol 478:373–374PubMedGoogle Scholar
  38. 38.
    Booth C, Evans G, Potten C (1995) Growth factor regulation of proliferation in primary cultures of small intestinal epithelium. In Vitro Cell Dev Biol Anim 31:234–243PubMedGoogle Scholar
  39. 39.
    Minekawa R, Takeda T, Sakata M, Hayashi M, Isobe A, Yamamoto T, Tasaka K, Murata Y (2004) Human breast milk suppresses the transcriptional regulation of IL-1beta-induced NF-kappaB signaling in human intestinal cells. Am J Physiol Cell Physiol 287:C1404–C1411PubMedGoogle Scholar
  40. 40.
    Takeda T, Sakata M, Minekawa R, Yamamoto T, Hayashi M, Tasaka K, Murata Y (2004) Human milk induces fetal small intestinal cell proliferation—involvement of a different tyrosine kinase signaling pathway from epidermal growth factor receptor. J Endocrinol 181:449–457PubMedGoogle Scholar
  41. 41.
    Grosvenor C, Picciano M, Baumrucker C (1993) Hormones and growth factors in milk. Endocrine Rev 14:710–728Google Scholar
  42. 42.
    Wagner CL, Purohit D (1999) Preface. Clinical aspects of human milk and lactation. Clin Perinatol 26:xi–xivGoogle Scholar
  43. 43.
    Newburg D (2001) Bioactive components of human milk. Evolution, efficiency and protection. Adv Exper Med Biol 501:3–10Google Scholar
  44. 44.
    Polk D (1992) Do breast milk derived hormones play a role in neonatal development. Early Hum Dev 29:329–331PubMedGoogle Scholar
  45. 45.
    Peaker M, Neville M (1991) Hormones in milk: chemical signals to the offspring? J Endocrinol 131:1–3PubMedGoogle Scholar
  46. 46.
    Koldovsky O (1989) Search for role of milk borne biologically active peptides for the suckling. J Nutr 119:1543–1551PubMedGoogle Scholar
  47. 47.
    Clark JA, Doelle SM, Halpern MD, Saunders TA, Holubec H, Dvorak K, Boitano SA, Dvorak B (2006) Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol 291:G938–G949Google Scholar
  48. 48.
    Moran J, Courtney M, Orth D, Vaughan R, Coy S, Mount C, Sherrell B, Greene H (1983) Epidermal growth factor in human milk: Daily production and diurnal variation during early lactation in mothers delivering at term and at premature gestation. J Pediatr 103:402–405PubMedGoogle Scholar
  49. 49.
    Gaull GE, Wright E, Isaacs CE (1985) Significance of growth modulators in human milk. Pediatrics 75:142–145PubMedGoogle Scholar
  50. 50.
    Wright E, Gaull G (1983) Nerve growth factor is present in human milk. Pediatr Res 17:144Google Scholar
  51. 51.
    Srivastava M, Lippes J, Srivastavabi S (1999) Hepatocyte growth factor in human milk and reproductive tract fluids. Am J Reprod Immunol 42:347–354PubMedGoogle Scholar
  52. 52.
    Baxter R, Zaltsman Z, Turtle J (1984) Immunoreactive somatomedin-C/insulin-like growth factor I and its binding protein in human milk. J Clin Endocrinal Metab 58:955–959Google Scholar
  53. 53.
    Shehadeh N, Shamir R, Berant M, Etzioni A (2001) Insulin in human milk and the prevention of type 1 diabetes. Pediatric Diabetes 2:175–177PubMedGoogle Scholar
  54. 54.
    Zumkeller W (1992) Relationship between insulin-like growth factor-I and -II and IGF-binding proteins in milk and the gastrointestinal tract: Growth and development of the gut. J Pediatr Gastroenterol Nutr 15:357–369PubMedGoogle Scholar
  55. 55.
    Donovan S, Hintz R, Rosenfeld R (1991) Insulin like growth factors I and II and their binding proteins in human milk: effect of heat treatment on IGF and IGF binding protein stability. J Pediatr Gastroenterol Nutr 13:242–253PubMedGoogle Scholar
  56. 56.
    Maheshwari A, Christensen RD, Calhoun DA (2003) ELR+ CXC chemokines in human milk. Cytokine 24:91–102PubMedGoogle Scholar
  57. 57.
    Bryan D-L, Forsyth KD, Gibson RA, Hawkes JS (2006) Interleukin-2 in human milk: A potential modulator of lymphocyte development in the breastfed infant. Cytokine 33:289–293PubMedGoogle Scholar
  58. 58.
    Garofalo R, Chheda S, Mei F, Palkowetz K, Rudloff H, Schmalstieg F, Rassin D, Goldman A (1995) Interleukin 10 in human milk. Pediatr Res 37:444–449PubMedGoogle Scholar
  59. 59.
    Okada M, Ohmura E, Kamiya Y, Murakami H, Onoda N, Iwashita M, Wakai K, Tsushima T, Shizume K (1991) Transforming growth factor (TGF)-alpha in human milk. Life Sci 48:1151–1156PubMedGoogle Scholar
  60. 60.
    Peptrides P, Hosang M, Shooter E, Bohlen P (1984) Transforming growth factors in human milk: isolation and partial chemical and biological characterization. In: Proc 7th Int Congress Endocr. p 1139Google Scholar
  61. 61.
    Wagner CL, Forsythe DW, Wagner MT (1998) The effect of recombinant TGFalpha, human milk, and human milk macrophage media on gut epithelial proliferation is decreased in the presence of a neutralizing TGFalpha antibody. Biol Neonate 74:363–371PubMedGoogle Scholar
  62. 62.
    Saito S, Yoshida M, Ichijo M, Tsujii T (1993) Transforming growth factor-beta in human milk. Clin Exp Immunol 94:220–224PubMedCrossRefGoogle Scholar
  63. 63.
    Hawkes J, Bryan D-L, James M, Gibson R (1999) Cytokines (IL-1[beta], IL-6, TNF-[alpha], TGF-[beta]1, and TGF-[beta]2) and Prostaglandin E2 in human milk during the first three months Postpartum. Pediatr Res 46:194–199PubMedGoogle Scholar
  64. 64.
    Eicher D, Wagner CL (1997) Vascular endothelial growth factor (VEGF) is present in human milk. Pediatr Res 41:478AGoogle Scholar
  65. 65.
    Siafakas C, Anatolitou F, Fusunyan R, Walker W, Sanderson I (1999) Vascular endothelial growth factor (VEGF) is present in human breast milk and its receptor is present on intestinal epithelial cells. Pediatr Res 45:652–657PubMedGoogle Scholar
  66. 66.
    Koldovsky O, Thornburg W (1987) Hormones in milk. J Pediatr Gastroenterol Nutr 6:172–196PubMedGoogle Scholar
  67. 67.
    Kling PJ, Sullivan TM, Roberts RA, Philipps AF, Koldovsky O (1998) Human milk as a potential enteral source of erythropoietin. Pediatr Res 43:216–221PubMedGoogle Scholar
  68. 68.
    Miller-Gilbert AL, Dubuque SH, Dvorak B, Williams CS, Grille JG, Woodward SS, Koldovsky O, Kling PJ (2001) Enteral absorption of erythropoietin in the suckling rat. Pediatr Res 50:261–267PubMedGoogle Scholar
  69. 69.
    Calhoun D, Lunoe M, Du Y, Christensen RD (2000) Granulocyte-stimulating colony factor is present in human milk and its receptor is present in human fetal intestines. Pediatrics 105:e7PubMedGoogle Scholar
  70. 70.
    Wagner C (2002) Amniotic fluid and human milk: A continuum of effect? [Editorial]. J Pediatr Gastroenterol Nutr 34:513–514PubMedGoogle Scholar
  71. 71.
    Rouwet EV, Heineman E, Buurman WA, ter Riet G, Ramsay G, Blanco CE (2002) Intestinal permeability and carrier-mediated monosaccharide absorption in preterm neonates during the early postnatal period. Pediatr Res 51:64–70PubMedGoogle Scholar
  72. 72.
    Weaver L, Laker M, Nelson R (1984) Intestinal permeability in the newborn. Arch Dis Child 59:236–241PubMedGoogle Scholar
  73. 73.
    Weaver LT, Laker MF, Nelson R, Lucas A (1987) Milk feeding and changes in intestinal permeability and morphology in the newborn. J Pediatr Gastroenterol Nutr 6:351–358PubMedGoogle Scholar
  74. 74.
    Lucas A, Cole T (1990) Breast milk and necrotizing enterocolitis. Lancet 336:1519–1523PubMedGoogle Scholar
  75. 75.
    Catassi C, Bonucci A, Coppa GV, Carlucci A, Giorgi PL (1995) Intestinal permeability changes during the first month: effect of natural versus artificial feeding. J Pediatr Gastroenterol Nutr 21:383–386PubMedGoogle Scholar
  76. 76.
    Iwamori M, Hirota K, Utsuki T, Momoeda K, Ono K, Tsuchida Y, Okumura K, Hanaoka K (1996) Sensitive method for the determination of pulmonary surfactant phospholipid/sphingomyelin ratio in human amniotic fluids for the diagnosis of respiratory distress syndrome by thin-layer chromatography-immunostaining. Analytical Biochem 238:29–33Google Scholar
  77. 77.
    Zeisel S, Char Z, Sheard N (1986) Choline, phosphatidylcholine and sphingomyelin in human and bovine milk and infant formulas. J Nutr 116:50–58PubMedGoogle Scholar
  78. 78.
    Motouri M, Matsuyama H, Yamamura J, Tanaka K, Aoe S, Iwanaga T, Kawakami H (2003) Milk sphingomyelin accelerates enzymatic and morphological maturation of the intestine in artificially reared rats. J Pediatr Gastroenterol Nutr 36:241–247PubMedGoogle Scholar
  79. 79.
    Perin N, Clandinin M, Thomson A (1997) Importance of milk and diet on ontogeny and adaptation of the intestine. J Pediatr Gastroenterol Nutr 24:419–425PubMedGoogle Scholar
  80. 80.
    Hanson L, Ceafalau L, Mattsby-Baltzer I, Lagerberg M, Hjalmarsson A, Ashraf R, Zaman S, Jalil F (2000) The mammary gland—infant intestine immunologic dyad. Adv Exp Med Biol 478:65–76PubMedGoogle Scholar
  81. 81.
    Wagner C, Forsythe D, Pittard W (1995) Variation in the biochemical forms of transforming growth factor-alpha present in human milk and secreted by human milk macrophages. Biol Neonate 68:325–333PubMedGoogle Scholar
  82. 82.
    Hanson L, Ahlstedt S, Anderson B, Carlsson B, Fallstrom S, Mellander L, Porras O, Soderstrom T, Eden C (1985) Protective factors in milk and the development of the immune system. Pediatrics 75:172–176PubMedGoogle Scholar
  83. 83.
    Hanson L, Andersson B, Carlsson B, Dahlgren U, Mellander L, Porras O, Svanborg Eden C, Soderstrom T (1985) The secretory IgA system. Klin Paediatr 197:330–333Google Scholar
  84. 84.
    Weaver L (2001) The child is father to the man. Clinical Medicine 1:38–43PubMedGoogle Scholar
  85. 85.
    Waterland R, Garza C (2002) Early postnatal nutrition determines adult pancreatic glucose-responsive insulin secretion and islet gene expression in rats. J Nutr 132:357–364PubMedGoogle Scholar
  86. 86.
    Waterland R, Lin J-R, Smith C, Jirtle R (2006) Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15:705–716PubMedGoogle Scholar
  87. 87.
    Weston W, Carson B, Barkin R, Seater G, Dusin R, Hect S (1977) Monocyte macrophage function in the newborn. Am J Dis Child 131:1241–1242PubMedGoogle Scholar
  88. 88.
    Klein R, Fischer T, Gard S, Biberstein M, Rich K, Stiehm E (1977) Defective mononuclear and polymorphonuclear chemotaxis in human newborns, infants, and young children. Pediatrics 60:467–472PubMedGoogle Scholar
  89. 89.
    Balda M, Fallon M, van Itallie C, Anderson J (1992) Structure, regulation, and pathophysiology of tight junctions in the gastrointestinal tract. Yale J Biol Med 65:725–735PubMedGoogle Scholar
  90. 90.
    Axelsson I, Jakobsson I, Lindberg T, Polberger S, Benediktsson B, Raiha N (1989) Macromolecular absorption in preterm and term infants. Acta Pediatr Scand 78:532–537Google Scholar
  91. 91.
    Schanler R (1997) Human milk for the premature infant. ABM News and Views 3:1–6Google Scholar
  92. 92.
    Schanler R, Hurst N, Lau C (1999) The use of human milk and breastfeeding in premature infants. Clin Perinatol 26:379–398PubMedGoogle Scholar
  93. 93.
    Jesse N, Neu J (2006) Necrotizing enterocolitis: Relationship to innate immunity, clinical features, and strategies for prevention. Neoreviews 7:e143–e150Google Scholar
  94. 94.
    Stevenson DK, Blakely ML (2006) Historical perspectives: necrotizing enterocolitis: an inherited or acquired condition? Neoreviews 7:e125–e134Google Scholar
  95. 95.
    Neu J, Mackey AD (2003) Neonatal gastrointestinal innate immunity. Neoreviews 4:e14–e19Google Scholar
  96. 96.
    He F, Morita H, Ouwehand A, Hosada M, Hiramatsu M, Kurisaka J-i, Benno Y, Salminen S (2002) Stimulation of the secretion of pro-inflammatory cytokines by bidifibacterium strains. Microbiol Immunol 46:781–785PubMedGoogle Scholar
  97. 97.
    Jensen R (ed) (1995) Handbook of milk composition. Academic, San DiegoGoogle Scholar
  98. 98.
    Ogra SS, Weintraub DI, Ogra PL (1978) Immunologic aspects of human colostrum and milk: interaction with the intestinal immunity of the neonate. Adv Exp Med Biol 107:95–107PubMedGoogle Scholar
  99. 99.
    Patton S, Keenan TW (1975) The milk fat globule membrane. Biochim Biophys Acta 415:273–309PubMedGoogle Scholar
  100. 100.
    Huston GE, Patton S (1986) Membrane distribution in human milks throughout lactation as revealed by phospholipid and cholesterol analyses. J Pediatr Gastroenterol Nutr 5:602–607PubMedCrossRefGoogle Scholar
  101. 101.
    Patton S, Borgstrom B, Stemberger BH, Welsch U (1986) Release of membrane from milk fat globules by conjugated bile salts. J Pediatr Gastroenterol Nutr 5:262–267PubMedGoogle Scholar
  102. 102.
    Patton S, Huston GE (1986) A method for isolation of milk fat globules. Lipids 21:170–174PubMedGoogle Scholar
  103. 103.
    Wagner C, Baatz J, Forsythe D, Virella G, Patton S (2002) TGFa is associated with the milk fat globule membrane. Adv Exper Med Biol 503:323–324Google Scholar
  104. 104.
    Crago S, Prince S, Pretlow T, McGhee J, Mestecky J (1979) Human colostral cells. I. Separation and characterization. Clin Exp Immunol 38:585–597PubMedGoogle Scholar
  105. 105.
    Smith C, Goldman A (1968) The cells of human colostrum. I. In vitro studies of morphology and function. Pediatr Res 2:103–109PubMedGoogle Scholar
  106. 106.
    Yoon BH, Jun JK, Park KH, Syn HC, Gomez R, Romero R (1996) Serum C-reactive protein, white blood cell count, and amniotic fluid white blood cell count in women with preterm premature rupture of membranes. Obstet Gynecol 88:1034–1040PubMedGoogle Scholar
  107. 107.
    Yoon B, Yang S, Jun J, Park K, Kim C, Romero R (1996) Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: A comparison with amniotic fluid white blood cell count. Obstet Gynecol 87:231–237PubMedGoogle Scholar
  108. 108.
    Maymon E, Romero R, Chaiworapongsa T, Kim JC, Berman S, Gomez R, Edwin S (2001) Value of amniotic fluid neutrophil collagenase concentrations in preterm premature rupture of membranes. Am J Obstet Gynecol 185:1143–1148PubMedGoogle Scholar
  109. 109.
    Widdowson E, Colombo V, Artavanis C (1976) Changes in the organs of pigs in response to feeding for the first 24 hour4s after birth. II. The digestive tract. Biol Neonate 23:272–281Google Scholar
  110. 110.
    Stoddart R, Widdowson E (1976) Changes in the organs of pigs in response to feeding for the first 24 hours after birth. III. Fluorescence histochemistry of the carbohydrates in the intestine. Biol Neonate 29:18–27PubMedGoogle Scholar
  111. 111.
    Widdowson EM (1984) Milk and the newborn animal. Proc Nutr Soc 43:87–100PubMedGoogle Scholar
  112. 112.
    Hall R, Widdowson EM (1979) Response of the organs of rabbits to feeding during the first days after birth. Biol Neonate 35:131–139PubMedCrossRefGoogle Scholar
  113. 113.
    Heird W, Schwarz S, Hansen I (1984) Colostrum-induced enteric mucosal growth in beagle puppies. Pediatr Res 18:512–515PubMedGoogle Scholar
  114. 114.
    Berseth C (1987) Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk. Am J Physiol 253:G662–G665PubMedGoogle Scholar
  115. 115.
    Oguchi S, Shinohara K, Yamashiro Y, Walker W, Sanderson I (1997) Growth factors in breast milk and their effect on gastrointestinal development. Acta Paed Sin 38:332–337Google Scholar
  116. 116.
    Ichiba H, Kusuda S, Itagane Y, Fujita K, Issiki G (1992) Measurement of growth promoting activity in human milk using a fetal small intestinal cell line. Biol Neonate 61:47–53PubMedGoogle Scholar
  117. 117.
    Kuitunen M, Savilahti E, Sarnesto A (1994) Human alpha-lactalbumin and bovine beta-lactoglobulin absorption in infants. Allergy 49:354–360PubMedGoogle Scholar
  118. 118.
    Kuitunen M, Savilahti E (1995) Mucosal IgA, mucosal cow's milk antibodies, serum cow's milk antibodies and gastrointestinal permeability in infants. Pediatr Allergy Immunol 6:30–35PubMedGoogle Scholar
  119. 119.
    Freed G, Fraley K, Schanler R (1992) Attitudes of expectant fathers regarding breast-feeding. Pediatrics 89:224–227Google Scholar
  120. 120.
    Kuitunen M, Savilahti E (1996) Gut permeability to human alpha-lactalbumin, beta-lactoglobulin, mannitol, and lactulose in celiac disease. J Pediatr Gastroenterol Nutr 22:197–204PubMedGoogle Scholar
  121. 121.
    Goto K, Chew F, Torun B, Peerson JM, Brown KH (1999) Epidemiology of altered intestinal permeability to lactulose and mannitol in Guatemalan infants. J Pediatr Gastroenterol Nutr 28:282–290PubMedGoogle Scholar
  122. 122.
    Bjarnason I, MacPherson A, Hollander D (1995) Intestinal permeability: an overview. Gastroenterology 108:1566–1581PubMedGoogle Scholar
  123. 123.
    Keating J, Bjarnason I, Somasundaram S, Macpherson A, Francis N, Price AB, Sharpstone D, Smithson J, Menzies IS, Gazzard BG (1995) Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea. Gut 37:623–629PubMedGoogle Scholar
  124. 124.
    Macpherson A, Khoo UY, Forgacs I, Philpott-Howard J, Bjarnason I (1996) Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut 38:365–375PubMedGoogle Scholar
  125. 125.
    Bjarnason I, Peters TJ (1996) Influence of anti-rheumatic drugs on gut permeability and on the gut associated lymphoid tissue. Baillieres Clin Rheumatol 10:165–176PubMedGoogle Scholar
  126. 126.
    Laker M, Bull HJ, Menzies I (1982) Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man. Eur J Clin Invest 12:485–491PubMedGoogle Scholar
  127. 127.
    Udall J, Colony P, Fritze L, Pang K, Trier J, Walker W (1981) Development of gastrointestinal mucosal barrier. II. The effect f natural versus artificial feeding on intestinal permeability to macromolecules. Pediatr Res 15:245–249PubMedGoogle Scholar
  128. 128.
    Adlerberth I, Hanson LA, Wold AE (1999) Ontogeny of the intestinal flora. In: Sanderson I, Walker W (eds) Development of the gastrointestinal tract. B. C. Decker, Hamilton, pp 279–292Google Scholar
  129. 129.
    Lindberg E, Nowrouzian F, Adlerberth I, Wold A (2000) Long-time persistence of superantigen-producing Staphylococcus aureus strains in the intestinal microfora of healthy infants. Pediatr Res 48:741–747PubMedGoogle Scholar
  130. 130.
    Hooper L (2004) Bacterial contributions to mammalian gut development. Trend Microbiol 12:129–134Google Scholar
  131. 131.
    Matsuki T, Watanabe K, Tanaka R, Fukuda M, Oyaizu H (1999) Distribution of bifidobacterial species in human intestinal microflora examined with 16S rRNA-gene-targeted species-specific primers. Appl Environ Microbiol 65:4506–4512PubMedGoogle Scholar
  132. 132.
    He F, Ouwehand A, Isolauri E et al (2001) Comparisonof mucosal adhesion and species identification of bifidobacteria isolated from healthy and allergic infants. FEMS Immunol Med Microbiol 30:43–47PubMedGoogle Scholar
  133. 133.
    Gueimonde M, Sakata S, Kalliomaki M, Isolauri E, Benno Y, Salminen S (2006) Effect of maternal consumption of Lactobacillus GG on transfer and establishment of fecal bifidobacterial microbiota in neonates. J Pediatr Gastroenterol Nutr 42:166–170PubMedGoogle Scholar
  134. 134.
    Benno Y, Sawada K, Mitsuoka T (1984) The intestinal microflora of infants: composition of fecal flora in breast fed and bottle fed infants. Microbiol Immunol 28:975–986PubMedGoogle Scholar
  135. 135.
    Kobayashi A, Kawai S, Ohbe Y, Benno Y (1988) Fecal flora of infants with biliary atresia: effects of absence of bile on fecal flora. Am J Clin Nutr 48:1211–1213PubMedGoogle Scholar
  136. 136.
    Mitsuoka T (1990) Bifidobacteria and their role in human health. J Ind Microbiol 6:263–268Google Scholar
  137. 137.
    Dewey K, Heinig M, Nommsen L (1995) Differences in morbidity between breast-fed and formula-fed infants. J Pediatr 126:696–702PubMedGoogle Scholar
  138. 138.
    Persson L, Ivarsson A, Hernell O (2002) Breast-feeding protects against celiac disease in childhood—epidemiological evidence. Adv Exp Med Biol 503:115–123PubMedGoogle Scholar
  139. 139.
    Howie P, Forsyth J, Ogston S, Clark A, du Florey C (1990) Protective effect of breast feeding against infection. BMJ 300:11–16PubMedGoogle Scholar
  140. 140.
    Zhang L, Li N, Neu J (2005) Probiotics for preterm infants. Neoreviews e6:227–232Google Scholar
  141. 141.
    Schnorr K, Pearson L (1984) Intestinal absorption of maternal leukocytes by newborn lambs. J Reprod Immunol 6:329–337PubMedGoogle Scholar
  142. 142.
    Goldman A, Smith CW (1973) Host resistance factors in human milk. J Pediatr 82:1082–1090PubMedGoogle Scholar
  143. 143.
    Jain L, Vidyasagar D, Xanthou M, Ghai V, Shimada S, Bend M (1989) In vivo distribution of human milk leukocytes after ingestion of newborn baboons. Arch Dis Child 64:930–933PubMedCrossRefGoogle Scholar
  144. 144.
    Paxson C, Cress CC (1979) Survival of human milk leukocytes. J Pediatr 94:61–64PubMedGoogle Scholar
  145. 145.
    Lessaris K, Forsythe D, Wagner C (2000) Effect of human milk fortifier on the immunodetection of transforming growth factor-a and its molecular mass profile. Biol Neonate 77:156–161PubMedGoogle Scholar
  146. 146.
    Outterridge P, Lee C (1981) Cellular immunity in the mammary gland with particular reference to T, B lymphocytes and macrophages. Adv Exp Med Biol 137:513–534Google Scholar
  147. 147.
    Schroten H, Kuczera F, Kohler H, Adam R (2000) Osponophagocytosis versus lectinophagocytososis in human milk macrophages. Adv Exp Med Biol 478:95–107PubMedCrossRefGoogle Scholar
  148. 148.
    Speer C, Gahr M, Pabst M (1986) Phagocytosi-associated oxidative metabolism in human milk macrophages. Acta Paediatr Scand 75:444–451PubMedGoogle Scholar
  149. 149.
    Tsuda H, Takeshige K, Shibata Y, Minakami S (1984) Oxygen metabolism of human colostral macrophages: comparison with monocytes and polymorphonuclear leukocytes. J Biochem (Tokyo) 95:1237–1245Google Scholar
  150. 150.
    Adam R, Kuczera F, Kohler H, Schroten H (2001) Superoxide anion generation in human milk macrophages: opsonin-dependent versus opsonin-independent stimulation compared with blood monocytes. Pediatr Res 49:435–439PubMedGoogle Scholar
  151. 151.
    Robinson G, Volovitz B, Passwell J (1991) Identification of a secretory IgA receptor on breast milk macrophages: Evidence for specific activation via these receptors. Pediatr Res 29:429–434PubMedGoogle Scholar
  152. 152.
    McPherson R, Wagner CL, Hollis B (1995) The secretion of TGFB2 by human milk macrophages (HMM). Pediatr Res 37:753AGoogle Scholar
  153. 153.
    Jatsyk G, Kuvaeva I, Gribakin S (1985) Immunological preparation of the neonatal gastrointestinal tract: The importance of breast feeding. Acta Pediatr Scand 74:246–249Google Scholar
  154. 154.
    Kretchmer N (1985) Gastrointestinal and immunologic development. Pediatrics 75:187–188Google Scholar
  155. 155.
    Selby W, Poulter L, Hobbs S, Jewell D, Janossy G (1983) Heterogeneity of HLA DR positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analyses. J Clin Pathol 36:379–384PubMedGoogle Scholar
  156. 156.
    Pittard WI, Polmar S, Fanaroff AA (1977) The breastmilk macrophage: a potential vehicle for immunoglobulin transport. J Reticuloendothel Soc 22:597–603PubMedGoogle Scholar
  157. 157.
    Hanson L, Korotkova M, Haversen L, Mattsby-Baltzer I, Hahn-Zoric M, Silfverdal S-A, Strandvik B, Telemo E (2002) Breast-feeding, a complex support system for the offspring. Pediatr Int 44:347–352PubMedGoogle Scholar
  158. 158.
    Hanson L, Korotkova M, Lundin S, Haversen L, Silfverdal S-A, Mattsby-Baltzer I, Strandvik B, Telemo E (2003) The transfer of immunity from mother to child. Ann NY Acad Sci 987:199–206PubMedGoogle Scholar
  159. 159.
    Hanson L, Silfverdal S-A, Korotkova M, Erling V, Strombeck L, Olcen P, Ulanova M, Hahn-Zoric M, Zaman S, Ashraf R et al (2002) Immune system modulation by human milk. In: Davis M, Isaacs C (eds) Integrating population outcomes, biological mechanisms and research methods in the study of human milk and lactation. Plenum, New York, pp 99–106Google Scholar
  160. 160.
    Newburg D (2000) Oligosaccharides in human milk and bacterial colonization. J Pediatr Gastroenterol Nutr 30:S8–S17PubMedGoogle Scholar
  161. 161.
    Hanson L, Carlsson B, Dahlgren U, Mellander L, Svanborg Eden C (1980) The secretory IgA system in the neonatal period. Ciba Found Symp 77:187–204Google Scholar
  162. 162.
    Hanson L, Korotkova M (2002) The role of breastfeeding in prevention of neonatal infection. Semin Neonatol 7:275–281PubMedGoogle Scholar
  163. 163.
    Medzhitov R, Janeway C (2000) Innate immunity. N Engl J Med 343:338–344PubMedGoogle Scholar
  164. 164.
    Haversen L, Ohlsson B, Hahn-Zoric M, Hanson L, Mattsby-Baltzer I (2002) Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kB. Cellular Immunology 220:83–95PubMedGoogle Scholar
  165. 165.
    Newburg D, Neubauer S (1995) Carbohydrates in milk. In: Jensen R (ed) Handbook of milk composition. Academic, San Diego, pp 273–349Google Scholar
  166. 166.
    Dai D, Nanthkumar N, Newburg D, Walker W (2000) Role of oligosaccharides and glycoconjugates in intestinal host defense. J Pediatr Gastroenterol Nutr 3:S23–S33Google Scholar
  167. 167.
    Newburg D (1996) Do the binding properties of oligosaccharides in milk protect human infants from gastrointestinal bacteria? J Nutr 127:980–984Google Scholar
  168. 168.
    Rao R, Baker S, Baker R, Wagner C, Schluter A (1998) A comparison of infant formula and human milk fortifier with human milk in the protection of intestinal epithelial barrier function. Pediatr Res 43:104AGoogle Scholar
  169. 169.
    Piena-Spoel M, Albers J, ten Kate J, Tibboel D (2001) Intestinal permeability in newborns with necrotizing enterocolitis and controls: does the sugar absorption test provide guidelines for the time to (re)introduce enteral nutrition? J Pediatr Surg 36:587–592PubMedGoogle Scholar
  170. 170.
    Dai S, Klagsbrun M, Shing YW (1985) Human milk-derived growth factor prevents doudenal ulcer formation. Pediatr Res 19(9):916–918, SeptGoogle Scholar
  171. 171.
    Klagsbrun M, Neumann J, Tapper D (1979) The mitogenic activity of human breast milk. J Surg Res 26(4):417–422, AprGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Carol L. Wagner
    • 1
  • Sarah N. Taylor
    • 1
  • Donna Johnson
    • 2
  1. 1.Division of Neonatology, Department of PediatricsMedical University of South CarolinaCharlestonUSA
  2. 2.Division of Maternal–Fetal Medicine, Department of Obstetrics and GynecologyMedical University of South CarolinaCharlestonUSA

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