Placental Inflammation

  • Raymond W. Redline

The placenta and fetus present a substantial challenge to the maternal immune system (Lu et al. 1991). Vigorous local immune responses can potentially activate maternal anti-fetal allograft immunity but a less than adequate local immune response would allow pathogens to enter the placenta and gain access to an immature fetal immune system that is ill-prepared to respond to them. Clearly, the balance between reactivity and suppression is most sorely tested when strong antigens such as microorganisms, alloantigens, novel placental antigens, or maternal autoantigens are expressed in the placental environment and become targets for maternal immunity. Irrespective of their etiology, the resulting immune responses can lead to adverse outcomes such as intrauterine fetal demise, premature delivery, fetal growth restriction, and organ-specific damage to the developing conceptus.

As is the case for all organs, the placenta and implantation site contain populations of resident inflammatory cells that are believed to play crucial roles in placental development and function. The two most prominent (and occasionally misinterpreted) resident populations are large granular lymphocytes in the decidualized endometrium and Hofbauer cells of the villous stroma. The former have been shown to consist primarily of natural killer cells and are believed to play a non-immunologic role in regulating maternal vascular remodeling and trophoblast invasion (Ashkar et al. 2000). They tend to cluster near endometrial glands and maternal vessels without any accompanying tissue damage. The latter are tissue mac-rophages believed to play a role in villous vascular development and in protection of the fetus from pathogens and other potentially harmful mediators that might inadvertently cross the maternal-fetal trophoblastic barrier (Wood 1983; Anteby et al. 2005). They tend to be monomorphic in appearance and are generally uniformly distributed throughout the villous stroma. They are most prominent in preterm placentas. Notably absent from the uteroplacental arena are neutrophils, eosinophils, and B and T lymphocytes. It is the presence of these latter cells that constitutes pathologic placental inflammation. Acute neutro-phil-dominated inflammatory responses (predominantly chorioamnionitis) are observed in approximately 20% of all delivered placentas and are virtually always the result of ascending bacterial infections from the cervicovaginal tract (Kraus et al. 2004). Chronic lymphocytic inflammatory responses occur in 5% to 15% of placentas and are with rare exceptions not associated with documented infection. To what extent these latter reactions represent autoimmune or alloimmune reactions versus the sequela of previous infections or infections by as yet unrecognized pathogens remains an open question at this time.


Bacterial Vaginosis Francisella Tularensis Congenital Syphilis Chronic Endometritis Histologic Chorioamnionitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abramowsky C, Beyer-Patterson P, Cortinas E (1991) Nonsyphilitic spirochetosis in second-trimester fetuses. Pediat Pathol 11:827–838.CrossRefGoogle Scholar
  2. Alba Greco M, Wieczorek R, Sachdev R, Kaplan C, Nuovo GJ, Demopoulos R (1992) Phenotype of villous stromal cells in placentas with cytomegalovirus, syphilis, and nonspecific villitis. Am J Pathol 141: 835–842.Google Scholar
  3. Altshuler G, Russell P (1975) The human placental vil-litides: a review of chronic intrauterine infection. Curr Topics Pathol 60:63–112.Google Scholar
  4. Anteby EY, Natanson-Yaron S, Greenfield C, et al. (2005) Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching. Placenta 26:476–483.PubMedCrossRefGoogle Scholar
  5. Ashkar AA, Di Santo JP, Croy BA (2000) Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 192:259–270.PubMedCrossRefGoogle Scholar
  6. Becroft DM, Thompson JM, Mitchell EA (2005) Placen-tal villitis of unknown origin: epidemiologic associations. Am J Obstet Gynecol 192:264–271.PubMedCrossRefGoogle Scholar
  7. Bendon R, Bornstein S, Faye-Petersen O (1998) Two fetal deaths associated with maternal sepsis and with thrombosis of the intervillous space of the placenta. Placenta 19:385–389.PubMedCrossRefGoogle Scholar
  8. Bittencourt AL (1976) Congenital Chagas disease. Am J Dis Child 130:97–103.PubMedGoogle Scholar
  9. Bittencourt AL, Garcia AG (2002) The placenta in hematogenous infections. Pediatr Pathol Mol Med 21:401–432.PubMedCrossRefGoogle Scholar
  10. Blanc W (1980) Pathology of the placenta and cord in ascending and hematogenous infections. In: Marshall W (ed) Perinatal Infections, CIBA Foundation Symposium 77. Excerpta Medica, London, pp. 17–38.CrossRefGoogle Scholar
  11. Boyd TK, Redline RW (2000) Chronic histiocytic inter-villositis: a placental lesion associated with recurrent reproductive loss. Hum Pathol 31:1389–1392.PubMedCrossRefGoogle Scholar
  12. Burgess AM, Hutchins GM (1996) Inflammation of the lungs, umbilical cord and placenta associated with meconium passage in utero. Review of 123 autopsied cases. Pathol Res Pract 192:1121–1128.PubMedGoogle Scholar
  13. Coid CR, Fox H (1983) Short review: campylobacters as placental pathogens. Placenta 4:295–306.PubMedCrossRefGoogle Scholar
  14. Dammann O, Allred EN, Leviton A, et al. (2004) Fetal vasculitis in preterm newborns: interrelationships, modifiers, and antecedents. Placenta 25:788–796.PubMedCrossRefGoogle Scholar
  15. DiSalvo D (1998) The correlation between placental pathology and intraventricular hemorrhage in the preterm infant. The Developmental Epidemiology Network Investigators. Pediatr Res 43:15–19.PubMedGoogle Scholar
  16. Doss BJ, Greene MF, Hill J, et al (1995) Massive chronic intervillositis associated with recurrent abortions. Hum Pathol 26:1245–1251.PubMedCrossRefGoogle Scholar
  17. Driscoll SG, Gorbach A, Feldman D (1962) Congenital listeriosis: diagnosis from placental studies. Obstet Gynecol 20:216–220.Google Scholar
  18. Elliott WG (1970) Placental Toxoplasmosis: report of a case. Am J Clin Pathol 53:413–417.PubMedGoogle Scholar
  19. Figueroa R, Bracero LA, Aguero-Rosenfeld M, Beneck D, Coleman J, Schwartz I (1996) Confirmation of Bor-relia burgdorferi spirochetes by polymerase chain reaction in placentas of women with reactive serol-ogy for Lyme antibodies. Gynecol Obstet Invest 41:240–243.PubMedCrossRefGoogle Scholar
  20. Fowler KB, Stagno S, Pass RF (2003) Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 289:1008–1011.PubMedCrossRefGoogle Scholar
  21. Fraser RB, Wright JR (2002) Eosinophilic/T-cell chori-onic vasculitis. Pediatr Devel Pathol 5:350–355.CrossRefGoogle Scholar
  22. Friedland JS, Jeffrey I, Griffin GE, Booker M, Courte-nay-Evans R (1994) Q fever and intrauterine death. Lancet 343:288.PubMedCrossRefGoogle Scholar
  23. Gersell DJ, Phillips NJ, Beckerman K (1991) Chronic chorioamnionitis: a clinicopathologic study of 17 cases. Int J Gynecol Pathol 10:217–229.PubMedCrossRefGoogle Scholar
  24. Goldenberg R, Hauth J, Andrews W (2000) Intrauterine infection and preterm delivery. N Engl J Med 342:1500–1507.PubMedCrossRefGoogle Scholar
  25. Gomez B, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM (1998) The fetal inflammatory response syndrome. Am J Obstet Gynecol 179:194–202.PubMedCrossRefGoogle Scholar
  26. Greenough A (1994) The TORCH screen and intrauter-ine infections. Arch Dis Child 70:F163–F165.Google Scholar
  27. Guzick DS, Winn K (1985) The association of chorio-amnionitis with preterm delivery. Obstet Gynecol 65:11–16.PubMedGoogle Scholar
  28. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA (1988). A case-control study of chorioamnionic infection and histologic chori-oamnionitis in prematurity. N Engl J Med 319: 972–980.PubMedCrossRefGoogle Scholar
  29. Hood IC, DeSa DJ, Whyte RK (1983) The inflammatory response in candidal chorioamnionitis. Hum Pathol 14:984–990.PubMedCrossRefGoogle Scholar
  30. Hyde SR, Benirschke K (1997) Gestational psittacosis: case report and literature review. Mod Pathol 10:602–607.PubMedGoogle Scholar
  31. Jacques S, Qureshi F (1998) Chronic chorioamnionitis: a clinicopathologic and immunohistochemical study. Hum Pathol 29:1457–1461.PubMedCrossRefGoogle Scholar
  32. Keenan WJ, Steichen JJ, Mahmood K, Altshuler G (1977) Placental pathology compared with clinical outcome. Am J Dis Child 131:1224–1227.PubMedGoogle Scholar
  33. Khong TY, Bendon RW, Qureshi F, et al. (2000) Chronic deciduitis in the placental basal plate: defini-tion and inter-observer reliability. Hum Pathol 31:292–295.PubMedCrossRefGoogle Scholar
  34. Kida M, Abramowsky CR, Santoscoy C (1989) Crypto-coccosis of the placenta in a woman with acquired immunodeficiency syndrome. Hum Pathol 20:920– 921.PubMedCrossRefGoogle Scholar
  35. Knowles S, Frost T (1989) Umbilical cord sclerosis as an indicator of congenital syphilis. J Clin Pathol 42:1157–1159.PubMedCrossRefGoogle Scholar
  36. Kraus FT, Redline R, Gersell DJ, Nelson DM, Dicke JM (2004) AFIP Atlas of Nontumor Pathology: Placental Pathology American Registry of Pathology, Washington, DC.Google Scholar
  37. Labarrere CA, Faulk W (1995) Maternal cells in chori-onic villi from placentae of normal and abnormal human pregnancies. Am J Reprod Immunol 33: 54–59.PubMedGoogle Scholar
  38. Langston C, Kaplan C, Macpherson T, et al. (1997) Practice guideline for examination of the placenta. Arch Pathol Lab Med 121:449–476.PubMedGoogle Scholar
  39. Lyon A (2000) Chronic lung disease of prematurity. The role of intra-uterine infection. Eur J Paediatr 159: 798–802.CrossRefGoogle Scholar
  40. Lu CY, Redline R, Dustin L, McKay DB, Shea CM (1991) Inhibition of macrophage and T-lymphocyte functions in the placenta and decidua during listeriosis: implications for tolerance of the fetoplacental allograft. In: Wegmann TG, Gill TJ 3rd, Nisbet-Brown E (eds) Immunobiology of the Maternal Fetal Interface. Oxford University Press, New York.Google Scholar
  41. Mamudo MR, Ordi J, Menendez C, et al. (2000) Placen-tal pathology in malaria: a histological, immunohis-tochemical and quantitative study. Hum Pathol 31:85–93.CrossRefGoogle Scholar
  42. Mostoufi-zadeh M, Driscoll SG, Biano SA, Kundsin RB (1984) Placental evidence of cytomegalovirus infection of the fetus and neonate. Arch Pathol Lab Med 108:403–406.PubMedGoogle Scholar
  43. Navarro C, Blanc WA (1974) Subacute necrotizing funisitis. A variant of cord inflammation with a high rate of perinatal infection. J Pediatr 85:689–697.Google Scholar
  44. Nijhuis EWP, van Nort G (1998) Clinicopathological correlations in chronic intervillositis. Pediatr Dev Pathol 1:457.Google Scholar
  45. Ohyama M, Fukui T, Tanaka Y, et al. (2001) Measles virus infection in the placenta of monozygotic twins. Mod Pathol 14:1300–1303.PubMedCrossRefGoogle Scholar
  46. Ohyama M, Itani Y, Yamanaka M, et al. (2002) Re-evaluation of chorioamnionitis and funisitis with a special reference to subacute chorioamnionitis. Hum Pathol 33:183–190.PubMedCrossRefGoogle Scholar
  47. O'Malley A, Gillan JE (2005) The incidence of viral infection causing villitis. Placenta 26:A.38.Google Scholar
  48. Ordi J, Ismail MR, Ventura PJ, et al. (1998) Massive chronic intervillositis of the placenta associated with malaria infection. Am J Surg Pathol 22: 1006–1011.PubMedCrossRefGoogle Scholar
  49. Qureshi F, Jacques SM, Benson RW, et al. (1998) Candida funisitis: A clinicopathologic study of 32 cases. Pediatr Dev Pathol 1:118–124.PubMedCrossRefGoogle Scholar
  50. Qureshi F, Jacques SM, Reyes MP (1993) Placental his-topathology in syphilis. Hum Pathol 24:779–784.PubMedCrossRefGoogle Scholar
  51. Redline RW (2004) Placental inflammation. Semin Neonatol 9:265–274.PubMedCrossRefGoogle Scholar
  52. Redline RW (2005) Severe fetal placental vascular lesions in term infants with neurologic impairment. Am J Obstet Gynecol 192:452–457.PubMedCrossRefGoogle Scholar
  53. Redline RW, Abramowsky CR (1985) Clinical and pathologic aspects of recurrent placental villitis. Hum Pathol 16:727–731.PubMedCrossRefGoogle Scholar
  54. Redline RW, Ariel I, Baergen RN, et al. (2004) Fetal vascular obstructive lesions: nosology and reproduc-ibility of placental reaction patterns. Pediatr Dev Pathol 7:443–452.PubMedCrossRefGoogle Scholar
  55. Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C (2003) Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol 6:435–448.PubMedCrossRefGoogle Scholar
  56. Redline RW, O'Riordan MA (2000) Placental lesions associated with cerebral palsy and neurologic impairment following term birth. Arch Pathol Lab Med 124:1785–1791.PubMedGoogle Scholar
  57. Redline RW, Patterson P (1993) Villitis of unknown etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells. Am J Pathol 143:473–479.PubMedGoogle Scholar
  58. Redline RW, Patterson P (1994) Patterns of placental injury: correlations with gestational age, placental weight, and clinical diagnosis. Arch Pathol Lab Med 118:698–701.PubMedGoogle Scholar
  59. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M (1998) Placental lesions associated with neurologic impairment and cerebral palsy in very low birth weight infants. Arch Pathol Lab Med 122:1091–1098.PubMedGoogle Scholar
  60. Renaud R, Brettes P, Castanier C, Loubiere R (1972) Placental bilharziasis. Int J Gynaecol Obstet 10:24– 30.Google Scholar
  61. Rogerson SJ, Beeson JG (1999) The placenta in malaria: mechanisms of infection, disease and foetal morbidity. Ann Trop Med Parasitol 93:S35–42.PubMedCrossRefGoogle Scholar
  62. Rogerson SJ, Pollina E, Getachew A, Tadesse E, Lema VM, Molyneux ME (2003) Placental monocyte infil-trates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes. Am J Trop Med Hyg 68:115–119.PubMedGoogle Scholar
  63. Salafia C, Silberman L, Herrera N, Mahoney M (1988) Placental pathology at term associated with elevated midtrimester serum alpha-fetoprotein concentration. Am J Obstet Gynecol 158:1064–1066.PubMedGoogle Scholar
  64. Steel JH, Malatos S, Kennea N, et al. (2005) Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res 57:404–411.PubMedCrossRefGoogle Scholar
  65. Styer AK, Parker HJ, Roberts DJ, Palmer-Toy D, Toth TL, Ecker JL (2003) Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy. Am J Obstet Gynecol 189:1184–1186.PubMedCrossRefGoogle Scholar
  66. Valderrama E (1992) Massive chronic intervillositis: Report of three cases. Lab Invest 66:10P.Google Scholar
  67. Vigneswaran R, Aitchison SJ, McDonald HM, Khong TY, Hiller JE (2004) Cerebral palsy and placental infection: a case-cohort study. BMC Pregn Childbirth 4:1471–1476.Google Scholar
  68. Walter PR, Garin Y, Blot P (1982). Placental pathologic changes in malaria. Am J Pathol 109:330– 342.PubMedGoogle Scholar
  69. Wood GW (1983) Role of macrophages in the elimination of anti-fetal antibody during its transport through the human placenta. Surv Synth Pathol Res 1:196–207.Google Scholar
  70. Xiao J, Garcia LG, Winklerlowen B, et al. (1997) ICAM-1–mediated adhesion of peripheral blood monocytes to the maternal surface of placental syncytiotropho-blasts: implications for placental villitis. Am J Pathol 150:1845–1860.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2007

Authors and Affiliations

  • Raymond W. Redline
    • 1
  1. 1.Department of Pathology and Reproductive BiologyCase School of Medicine, Institute of PathologyClevelandUSA

Personalised recommendations