Semin Reprod Med 2007; 25(1): 021-039
DOI: 10.1055/s-2006-956773
Copyright © 2007 by Thieme Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Inflammation and Infection in Preterm Birth

Roberto Romero1 , 2 , Jimmy Espinoza1 , 3 , Luís F. Gonçalves1 , 3 , Juan Pedro Kusanovic1 , Lara Friel3 , Sonia Hassan1 , 3
  • 1Perinatology Research Branch, National Instituted of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan
  • 2Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan
  • 3Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
05. Januar 2007 (online)

ABSTRACT

Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labor and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labor, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. This article reviews the role of inflammation in preterm and term parturition.

REFERENCES

  • 1 Brocklehurst P. Infection and preterm delivery.  BMJ. 1999;  318 548-549
  • 2 Gibbs R S, Romero R, Hillier S L, Eschenbach D A, Sweet R L. A review of premature birth and subclinical infection.  Am J Obstet Gynecol. 1992;  166 1515-1528
  • 3 Goldenberg R L, Hauth J C, Andrews W W. Intrauterine infection and preterm delivery.  N Engl J Med. 2000;  342 1500-1507
  • 4 Ledger W J. Infection and premature labor.  Am J Perinatol. 1989;  6 234-236
  • 5 Minkoff H. Prematurity: infection as an etiologic factor.  Obstet Gynecol. 1983;  62 137-144
  • 6 Naeye R L, Ross S M. Amniotic fluid infection syndrome.  Clin Obstet Gynaecol. 1982;  9 593-607
  • 7 Romero R, Mazor M. Infection and preterm labor.  Clin Obstet Gynecol. 1988;  31 553-584
  • 8 Romero R, Mazor M, Wu Y K et al.. Infection in the pathogenesis of preterm labor.  Semin Perinatol. 1988;  12 262-279
  • 9 Gomez R, Romero R, Ghezzi F et al.. The fetal inflammatory response syndrome.  Am J Obstet Gynecol. 1998;  179 194-202
  • 10 Romero R, Gomez R, Ghezzi F et al.. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.  Am J Obstet Gynecol. 1998;  179 186-193
  • 11 Romero R, Mazor M, Munoz H et al.. The preterm labor syndrome.  Ann N Y Acad Sci. 1994;  734 414-429
  • 12 Henson P M. Dampening inflammation.  Nat Immunol. 2005;  6 1179-1181
  • 13 Ley K. History of inflammation research. In: Lee K Physiology of Inflammation. New York; Oxford University Press 2001: 1-10
  • 14 Cotran R S. Inflammation: historical perspectives. In: Gallin JI, Snyderman R, eds. Inflammation. Basic Principles and Clinical Correlates, 3rd ed. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 5-10
  • 15 Janeway C, Travers P, Walport M, Schlomchik M. Innate immunity. In: Immunobiology. 6th ed. New York; Garland Science 2005: 37-102
  • 16 Salamonsen L A, Lathbury L J. Endometrial leukocytes and menstruation.  Hum Reprod Update. 2000;  6 16-27
  • 17 Kiviat N B, Wolner-Hanssen P, Eschenbach D A et al.. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis.  Am J Surg Pathol. 1990;  14 167-175
  • 18 Haddad R, Tromp G, Kuivaniemi H et al.. Spontaneous labor at term is characterized by a genomic signature of acute inflammation in the chorioamniotic membranes but not in the systemic circulation.  Am J Obstet Gynecol. 2004;  191 S138
  • 19 Yoon B H, Romero R, Moon J B et al.. Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes.  Am J Obstet Gynecol. 2001;  185 1130-1136
  • 20 Yoon B H, Romero R, Park J S et al.. The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis.  Am J Obstet Gynecol. 2000;  183 1124-1129
  • 21 Metchnikoff E. Lectures on the Comparative Pathology of Inflammation (reprint of the 1983 English translation). New York; Dover 1968
  • 22 Brannstrom M, Enskog A. Leukocyte networks and ovulation.  J Reprod Immunol. 2002;  57 47-60
  • 23 Chard T. Cytokines in implantation.  Hum Reprod Update. 1995;  1 385-396
  • 24 Finn C A. Implantation, menstruation and inflammation.  Biol Rev Camb Philos Soc. 1986;  61 313-328
  • 25 Kelly R W, King A E, Critchley H O. Inflammatory mediators and endometrial function-focus on the perivascular cell.  J Reprod Immunol. 2002;  57 81-93
  • 26 Keelan J A, Blumenstein M, Helliwell R J et al.. Cytokines, prostaglandins and parturition-a review.  Placenta. 2003;  24(suppl A) S33-S46
  • 27 Romero R, Parvizi S T, Oyarzun E et al.. Amniotic fluid interleukin-1 in spontaneous labor at term.  J Reprod Med. 1990;  35 235-238
  • 28 Salvemini D, Cuzzocrea S. Oxidative stress in septic shock and disseminated intravascular coagulation.  Free Radic Biol Med. 2002;  33 1173-1185
  • 29 Redman C W, Sargent I L. Placental debris, oxidative stress and pre-eclampsia.  Placenta. 2000;  21 597-602
  • 30 Roberts J M, Hubel C A. Is oxidative stress the link in the two-stage model of pre-eclampsia?.  Lancet. 1999;  354 788-789
  • 31 Dekker G A, Sibai B M. The immunology of preeclampsia.  Semin Perinatol. 1999;  23 24-33
  • 32 Morris J M, Gopaul N K, Endresen M J et al.. Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.  Br J Obstet Gynaecol. 1998;  105 1195-1199
  • 33 Hoffman M, Cooper S T. Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms.  Blood Cells Mol Dis. 1995;  21 156-167
  • 34 Matzinger P. The danger model: a renewed sense of self.  Science. 2002;  296 301-305
  • 35 Hashimoto C, Hudson K L, Anderson K V. The Toll gene of drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein.  Cell. 1988;  52 269-279
  • 36 Medzhitov R, Janeway J. The Toll receptor family and microbial recognition.  Trends Microbiol. 2000;  8 452-456
  • 37 Beg A A. Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses.  Trends Immunol. 2002;  23 509-512
  • 38 Romero R, Sirtori M, Oyarzun E et al.. Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes.  Am J Obstet Gynecol. 1989;  161 817-824
  • 39 Goncalves L F, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity.  Ment Retard Dev Disabil Res Rev. 2002;  8 3-13
  • 40 Zahl P A, Bjerknes C. Induction of decidua-placental hemorrhage in mice by the endotoxins of certain gram-negative bacteria.  Proc Soc Exp Biol Med. 1943;  54 329-332
  • 41 Takeda Y, Tsuchiya I. Studies on the pathological changes caused by the injection of the Shwartzman filtrate and the endotoxin into pregnant rabbits.  Jpn J Exp Med. 1953;  21 9-16
  • 42 Rieder R F, Thomas L. Studies on the mechanisms involved in the production of abortion by endotoxin.  J Immunol. 1960;  84 189-193
  • 43 McKay D G, Wong T C. The effect of bacterial endotoxin on the placenta of the rat.  Am J Pathol. 1963;  42 357-377
  • 44 Skarnes R C, Harper M J. Relationship between endotoxin-induced abortion and the synthesis of prostaglandin F.  Prostaglandins. 1972;  1 191-203
  • 45 Kullander S. Fever and parturition. An experimental study in rabbits.  Acta Obstet Gynecol Scand Suppl. 1977;  66 77-85
  • 46 Bang B. The etiology of epizootic abortion.  J Comp Anthol Ther. 1987;  10 125
  • 47 McDuffie Jr R S, Sherman M P, Gibbs R S. Amniotic fluid tumor necrosis factor-alpha and interleukin-1 in a rabbit model of bacterially induced preterm pregnancy loss.  Am J Obstet Gynecol. 1992;  167 1583-1588
  • 48 Fidel Jr P L, Romero R, Wolf N et al.. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice.  Am J Obstet Gynecol. 1994;  170 1467-1475
  • 49 Romero R, Munoz H, Gomez R et al.. Antibiotic therapy reduces the rate of infection-induced preterm delivery and perinatal mortality.  Am J Obstet Gynecol. 1994;  170 390
  • 50 Gravett M G, Witkin S S, Haluska G J et al.. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys.  Am J Obstet Gynecol. 1994;  171 1660-1667
  • 51 Gravett M G, Haluska G J, Cook M J, Novy M J. Fetal and maternal endocrine responses to experimental intrauterine infection in rhesus monkeys.  Am J Obstet Gynecol. 1996;  174 1725-1731
  • 52 Elovitz M A, Mrinalini C. Animal models of preterm birth.  Trends Endocrinol Metab. 2004;  15 479-487
  • 53 Gilles H M, Lawson J B, Sibelas M, Voller A, Allan N. Malaria, anaemia and pregnancy.  Ann Trop Med Parasitol. 1969;  63 245-263
  • 54 Herd N, Jordan T. An investigation of malaria during pregnancy in Zimbabwe.  Cent Afr J Med. 1981;  27 62-68
  • 55 McGuire W, Hill A V, Allsopp C E, Greenwood B M, Kwiatkowski D. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria.  Nature. 1994;  371 508-510
  • 56 Osman N B, Folgosa E, Gonzales C, Bergstrom S. Genital infections in the aetiology of late fetal death: an incident case-referent study.  J Trop Pediatr. 1995;  41 258-266
  • 57 Folgosa E, Gonzalez C, Osman N B et al.. A case control study of chorioamniotic infection and histological chorioamnionitis in stillbirth.  APMIS. 1997;  105 329-336
  • 58 Kalanda B F, Verhoeff F H, Chimsuku L, Harper G, Brabin B J. Adverse birth outcomes in a malarious area.  Epidemiol Infect. 2006;  134 659-666
  • 59 Hibbard L, Thrupp L, Summeril S, Smale M, Adams R. Treatment of pyelonephritis in pregnancy.  Am J Obstet Gynecol. 1967;  98 609-615
  • 60 Patrick M J. Influence of maternal renal infection on the foetus and infant.  Arch Dis Child. 1967;  42 208-213
  • 61 Wren B G. Subclinical renal infection and prematurity.  Med J Aust. 1969;  2 596-600
  • 62 Cunningham F G, Morris G B, Mickal A. Acute pyelonephritis of pregnancy: a clinical review.  Obstet Gynecol. 1973;  42 112-117
  • 63 Fan Y D, Pastorek J G, Miller Jr J M, Mulvey J. Acute pyelonephritis in pregnancy.  Am J Perinatol. 1987;  4 324-326
  • 64 Benedetti T J, Valle R, Ledger W J. Antepartum pneumonia in pregnancy.  Am J Obstet Gynecol. 1982;  144 413-417
  • 65 Goepfert A R, Jeffcoat M K, Andrews W W et al.. Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth.  Obstet Gynecol. 2004;  104 777-783
  • 66 Jarjoura K, Devine P C, Perez-Delboy A et al.. Markers of periodontal infection and preterm birth.  Am J Obstet Gynecol. 2005;  192 513-519
  • 67 Xiong X, Buekens P, Fraser W D, Beck J, Offenbacher S. Periodontal disease and adverse pregnancy outcomes: a systematic review.  BJOG. 2006;  113 135-143
  • 68 Offenbacher S, Boggess K A, Murtha A P et al.. Progressive periodontal disease and risk of very preterm delivery.  Obstet Gynecol. 2006;  107 29-36
  • 69 Gomez R, Ghezzi F, Romero R et al.. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology.  Clin Perinatol. 1995;  22 281-342
  • 70 Cassell G H, Davis R O, Waites K B et al.. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16-20 weeks of gestation: potential effect on outcome of pregnancy.  Sex Transm Dis. 1983;  10 294-302
  • 71 Gray D J, Robinson H B, Malone J, Thomson Jr R B. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum .  Prenat Diagn. 1992;  12 111-117
  • 72 Horowitz S, Mazor M, Romero R, Horowitz J, Glezerman M. Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy.  J Reprod Med. 1995;  40 375-379
  • 73 Romero R, Munoz H, Gomez R et al.. Two thirds of spontaneous abortion/fetal deaths after genetic amniocentesis are the result of a pre-existing sub-clinical inflammatory process of the amniotic cavity.  Am J Obstet Gynecol. 1995;  172 S261(Abst)
  • 74 Wenstrom K D, Andrews W W, Hauth J C et al.. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery.  Am J Obstet Gynecol. 1998;  178 546-550
  • 75 Yoon B H, Oh S Y, Romero R et al.. An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.  Am J Obstet Gynecol. 2001;  185 1162-1167
  • 76 Fidel P, Ghezzi F, Romero R et al.. The effect of antibiotic therapy on intrauterine infection-induced preterm parturition in rabbits.  J Matern Fetal Neonatal Med. 2003;  14 57-64
  • 77 Romero R, Oyarzun E, Mazor M et al.. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight.  Obstet Gynecol. 1989;  73 576-582
  • 78 Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy.  Cochrane Database Syst Rev. 2001;  2 CD000490
  • 79 Romero R, Quintero R, Oyarzun E et al.. Intraamniotic infection and the onset of labor in preterm premature rupture of the membranes.  Am J Obstet Gynecol. 1988;  159 661-666
  • 80 Romero R, Gonzalez R, Sepulveda W et al.. Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.  Am J Obstet Gynecol. 1992;  167 1086-1091
  • 81 Mays J K, Figueroa R, Shah J et al.. Amniocentesis for selection before rescue cerclage.  Obstet Gynecol. 2000;  95 652-655
  • 82 Hassan S, Romero R, Hendler I et al.. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection.  J Perinat Med. 2006;  34 13-19
  • 83 Mazor M, Hershkovitz R, Ghezzi F et al.. Intraamniotic infection in patients with preterm labor and twin pregnancies.  Acta Obstet Gynecol Scand. 1996;  75 624-627
  • 84 Romero R, Shamma F, Avila C et al.. Infection and labor. VI. Prevalence, microbiology, and clinical significance of intraamniotic infection in twin gestations with preterm labor.  Am J Obstet Gynecol. 1990;  163 757-761
  • 85 Watts D H, Krohn M A, Hillier S L, Eschenbach D A. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor.  Obstet Gynecol. 1992;  79 351-357
  • 86 Andrews W W, Hauth J C, Goldenberg R L et al.. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery.  Am J Obstet Gynecol. 1995;  173 606-612
  • 87 Romero R, Mazor M, Morrotti R et al.. Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term.  Am J Obstet Gynecol. 1992;  166 129-133
  • 88 Bearfield C, Davenport E S, Sivapathasundaram V, Allaker R P. Possible association between amniotic fluid micro-organism infection and microflora in the mouth.  BJOG. 2002;  109 527-533
  • 89 Amann R I, Ludwig W, Schleifer K H. Phylogenetic identification and in situ detection of individual microbial cells without cultivation.  Microbiol Rev. 1995;  59 143-169
  • 90 Relman D A. The search for unrecognized pathogens.  Science. 1999;  284 1308-1310
  • 91 Ranjard L, Poly F, Nazaret S. Monitoring complex bacterial communities using culture-independent molecular techniques: application to soil environment.  Res Microbiol. 2000;  151 167-177
  • 92 Relman D A, Loutit J S, Schmidt T M, Falkow S, Tompkins L S. The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens.  N Engl J Med. 1990;  323 1573-1580
  • 93 Jalava J, Mantymaa M L, Ekblad U et al.. Bacterial 16S rDNA polymerase chain reaction in the detection of intra-amniotic infection.  Br J Obstet Gynaecol. 1996;  103 664-669
  • 94 Hitti J, Riley D E, Krohn M A et al.. Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting amniotic fluid infection among women in premature labor.  Clin Infect Dis. 1997;  24 1228-1232
  • 95 Gardella C, Riley D E, Hitti J et al.. Identification and sequencing of bacterial rDNAs in culture-negative amniotic fluid from women in premature labor.  Am J Perinatol. 2004;  21 319-323
  • 96 Yoon B H, Romero R, Kim M et al.. Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction.  Am J Obstet Gynecol. 2000;  183 1130-1137
  • 97 Yoon B H, Romero R, Lim J H et al.. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor.  Am J Obstet Gynecol. 2003;  189 919-924
  • 98 Steel J H, Malatos S, Kennea N et al.. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor.  Pediatr Res. 2005;  58 404-411 (Abst)
  • 99 Offenbacher S, Beck J D, Lieff S, Slade G. Role of periodontitis in systemic health: spontaneous preterm birth.  J Dent Educ. 1998;  62 852-858
  • 100 Jeffcoat M K, Geurs N C, Reddy M S et al.. Periodontal infection and preterm birth: results of a prospective study.  J Am Dent Assoc. 2001;  132 875-880
  • 101 Madianos P N, Lieff S, Murtha A P et al.. Maternal periodontitis and prematurity. Part II: maternal infection and fetal exposure.  Ann Periodontol. 2001;  6 175-182
  • 102 Offenbacher S, Lieff S, Boggess K A et al.. Maternal periodontitis and prematurity. Part I: obstetric outcome of prematurity and growth restriction.  Ann Periodontol. 2001;  6 164-174
  • 103 Khader Y S, Ta'ani Q. Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis.  J Periodontol. 2005;  76 161-165
  • 104 Boggess K A, Madianos P N, Preisser J S, Moise J, Offenbacher S. Chronic maternal and fetal Porphyromonas gingivalis exposure during pregnancy in rabbits.  Am J Obstet Gynecol. 2005;  192 554-557
  • 105 Downey J S, Han J. Cellular activation mechanisms in septic shock.  Front Biosci. 1998;  3 d468-d476
  • 106 Wang J E, Dahle M K, McDonald M et al.. Peptidoglycan and lipoteichoic acid in gram-positive bacterial sepsis: receptors, signal transduction, biological effects, and synergism.  Shock. 2003;  20 402-414
  • 107 Smith P F. Lipoglycans from mycoplasmas.  Crit Rev Microbiol. 1984;  11 157-186
  • 108 Romero R, Kadar N, Hobbins J C, Duff G W. Infection and labor: the detection of endotoxin in amniotic fluid.  Am J Obstet Gynecol. 1987;  157 815-819
  • 109 Romero R, Roslansky P, Oyarzun E et al.. Labor and infection. II. Bacterial endotoxin in amniotic fluid and its relationship to the onset of preterm labor.  Am J Obstet Gynecol. 1988;  158 1044-1049
  • 110 Elovitz M A, Wang Z, Chien E K, Rychlik D F, Phillippe M. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4.  Am J Pathol. 2003;  163 2103-2111
  • 111 Grigsby P L, Hirst J J, Scheerlinck J P, Phillips D J, Jenkin G. Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep.  Biol Reprod. 2003;  68 1695-1702
  • 112 Evaldson G, Malmborg A S, Nord C E, Ostensson K. Bacteroides fragilis, Streptococcus intermedius and group B streptococci in ascending infection of pregnancy. An animal experimental study.  Gynecol Obstet Invest. 1983;  15 230-241
  • 113 Kajikawa S, Kaga N, Futamura Y, Kakinuma C, Shibutani Y. Lipoteichoic acid induces preterm delivery in mice.  J Pharmacol Toxicol Methods. 1998;  39 147-154
  • 114 Jobe A H, Newnham J P, Willet K E et al.. Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol.  Am J Respir Crit Care Med. 2000;  162 1656-1661
  • 115 Jobe A H, Newnham J P, Willet K E et al.. Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs.  Am J Obstet Gynecol. 2000;  182 401-408
  • 116 Jobe A H. Antenatal associations with lung maturation and infection.  J Perinatol. 2005;  25(suppl 2) S31-S35
  • 117 Yoon B H, Kim C J, Romero R et al.. Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits.  Am J Obstet Gynecol. 1997;  177 797-802
  • 118 McLean L K, Chehab F F, Goldberg J D. Detection of viral deoxyribonucleic acid in the amniotic fluid of low-risk pregnancies by polymerase chain reaction.  Am J Obstet Gynecol. 1995;  173 1282-1286
  • 119 Yankowitz J, Weiner C P, Henderson J, Grant S, Towbin J. Outcome of low-risk pregnancies with evidence of intraamniotic viral infection detected by PCR on amniotic fluid obtained at second trimester genetic amniocenteses.  J Soc Gynecol Investig. 1996;  3 132A
  • 120 Wenstrom K D, Andrews W W, Bowles N E et al.. Intrauterine viral infection at the time of second trimester genetic amniocentesis.  Obstet Gynecol. 1998;  92 420-424
  • 121 Baschat A A, Towbin J, Bowles N E, Harman C R, Weiner C P. Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester.  J Matern Fetal Neonatal Med. 2003;  13 381-384
  • 122 Van den Veyver I B, Ni J, Bowles N et al.. Detection of intrauterine viral infection using the polymerase chain reaction.  Mol Genet Metab. 1998;  63 85-95
  • 123 Baschat A A, Harman C R, Towbin J A, Weiner C P. Fetal sonographic abnormalities and intrauterine viral infection.  Am J Obstet Gynecol. 2000;  182 S95(Abst)
  • 124 Reddy U, Zlatnik M, Baschat A A et al.. Detection of viral deoxyribonucleic acid in amniotic fluid: predictor of abnormal pregnancy.  Am J Obstet Gynecol. 2001;  185 S192 (Abst)
  • 125 Burguete T, Rabreau M, Fontanges-Darriet M et al.. Evidence for infection of the human embryo with adeno-associated virus in pregnancy.  Hum Reprod. 1999;  14 2396-2401
  • 126 Galask R P, Varner M W, Petzold C R, Wilbur S L. Bacterial attachment to the chorioamniotic membranes.  Am J Obstet Gynecol. 1984;  148 915-928
  • 127 King A E, Critchley H O, Kelly R W. Innate immune defences in the human endometrium.  Reprod Biol Endocrinol. 2003;  1 116
  • 128 Matsuzaki K. Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes.  Biochim Biophys Acta. 1999;  1462 1-10
  • 129 Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides.  Biochim Biophys Acta. 1999;  1462 55-70
  • 130 Yang L, Weiss T M, Lehrer R I, Huang H W. Crystallization of antimicrobial pores in membranes: magainin and protegrin.  Biophys J. 2000;  79 2002-2009
  • 131 Zasloff M. Antimicrobial peptides of multicellular organisms.  Nature. 2002;  415 389-395
  • 132 Condon J C, Jeyasuria P, Faust J M, Mendelson C R. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition.  Proc Natl Acad Sci USA. 2004;  101 4978-4983
  • 133 Mori K, Kurihara N, Hayashida S, Tanaka M, Ikeda K. The intrauterine expression of surfactant protein D in the terminal airways of human fetuses compared with surfactant protein A.  Eur J Pediatr. 2002;  161 431-434
  • 134 Kishore U, Bernal A L, Kamran M F et al.. Surfactant proteins SP-A and SP-D in human health and disease.  Arch Immunol Ther Exp (Warsz). 2005;  53 399-417
  • 135 Costerton W, Veeh R, Shirtliff M et al.. The application of biofilm science to the study and control of chronic bacterial infections.  J Clin Invest. 2003;  112 1466-1477
  • 136 McGroarty J A, Reid G. Detection of a Lactobacillus substance that inhibits Escherichia coli .  Can J Microbiol. 1988;  34 974-978
  • 137 Reid G, Burton J. Use of Lactobacillus to prevent infection by pathogenic bacteria.  Microbes Infect. 2002;  4 319-324
  • 138 Hargreaves D C, Medzhitov R. Innate sensors of microbial infection.  J Clin Immunol. 2005;  25 503-510
  • 139 Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity.  Microbes Infect. 2004;  6 1382-1387
  • 140 Way S S, Thompson L J, Lopes J E et al.. Characterization of flagellin expression and its role in Listeria monocytogenes infection and immunity.  Cell Microbiol. 2004;  6 235-242
  • 141 Fazeli A, Bruce C, Anumba D O. Characterization of Toll-like receptors in the female reproductive tract in humans.  Hum Reprod. 2005;  20 1372-1378
  • 142 Abrahams V M, Bole-Aldo P, Kim Y M et al.. Divergent trophoblast responses to bacterial products mediated by TLRs.  J Immunol. 2004;  173 4286-4296
  • 143 Vadillo Ortega F, Avila Vergara M A, Hernandez G C, Arechavaleta V F, Beltran M J. Apoptosis in trophoblast of patients with recurrent spontaneous abortion of unidentified cause.  Ginecol Obstet Mex. 2000;  68 122-131
  • 144 Huppertz B, Hemmings D, Renaud S J et al.. Extravillous trophoblast apoptosis-a workshop report.  Placenta. 2005;  26(suppl A) S46-S48
  • 145 Murthi P, Kee M W, Gude N M, Brennecke S P, Kalionis B. Fetal growth restriction is associated with increased apoptosis in the chorionic trophoblast cells of human fetal membranes.  Placenta. 2005;  26 329-338
  • 146 Neale D M, Mor G. The role of Fas mediated apoptosis in preeclampsia.  J Perinat Med. 2005;  33 471-477
  • 147 Wang H, Hirsch E. Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of toll-like receptor 4.  Biol Reprod. 2003;  69 1957-1963
  • 148 Kim Y M, Romero R, Chaiworapongsa T et al.. Toll-like receptor-2 and -4 in the chorioamniotic membranes in spontaneous labor at term and in preterm parturition that are associated with chorioamnionitis.  Am J Obstet Gynecol. 2004;  191 1346-1355
  • 149 Romero R, Durum S K, Dinarello C A et al.. Interleukin-1: a signal for the initiation of labor in chorioamnionitis. Presented at: 33rd Annual Meeting for the Society for Gynecologic Investigation 1986 Toronto, Canada;
  • 150 Challis J R, Lye S J, Gibb W et al.. Understanding preterm labor.  Ann NY Acad Sci. 2001;  943 225-234
  • 151 Goldenberg R L, Andrews W W, Hauth J C. Choriodecidual infection and preterm birth.  Nutr Rev. 2002;  60 S19-S25
  • 152 Menon R, Fortunato S J. Fetal membrane inflammatory cytokines: a switching mechanism between the preterm premature rupture of the membranes and preterm labor pathways.  J Perinat Med. 2004;  32 391-399
  • 153 Mohan A R, Loudon J A, Bennett P R. Molecular and biochemical mechanisms of preterm labour.  Semin Fetal Neonatal Med. 2004;  9 437-444
  • 154 Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G. Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role for genetic epidemiology in the prevention of preterm birth.  Am J Obstet Gynecol. 2004;  190 1509-1519
  • 155 Romero R, Espinoza J, Mazor M. Can endometrial infection/inflammation explain implantation failure, spontaneous abortion, and preterm birth after in vitro fertilization?.  Fertil Steril. 2004;  82 799-804
  • 156 Hagberg H, Mallard C, Jacobsson B. Role of cytokines in preterm labour and brain injury.  BJOG. 2005;  112(suppl 1) 16-18
  • 157 Hirsch E, Wang H. The molecular pathophysiology of bacterially induced preterm labor: insights from the murine model.  J Soc Gynecol Investig. 2005;  12 145-155
  • 158 Lindstrom T M, Bennett P R. The role of nuclear factor kappa B in human labour.  Reproduction. 2005;  130 569-581
  • 159 Vogel I, Thorsen P, Curry A, Sandager P, Uldbjerg N. Biomarkers for the prediction of preterm delivery.  Acta Obstet Gynecol Scand. 2005;  84 516-525
  • 160 Romero R, Wu Y K, Brody D T et al.. Human decidua: a source of interleukin-1.  Obstet Gynecol. 1989;  73 31-34
  • 161 Romero R, Durum S, Dinarello C A et al.. Interleukin-1 stimulates prostaglandin biosynthesis by human amnion.  Prostaglandins. 1989;  37 13-22
  • 162 Romero R, Brody D T, Oyarzun E et al.. Infection and labor. III. Interleukin-1: a signal for the onset of parturition.  Am J Obstet Gynecol. 1989;  160 1117-1123
  • 163 Sadowsky D W, Novy M J, Witkin S S, Gravett M G. Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys.  Am J Obstet Gynecol. 2003;  188 252-263
  • 164 Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice.  Am J Obstet Gynecol. 1991;  165 969-971
  • 165 Romero R, Tartakovsky B. The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice.  Am J Obstet Gynecol. 1992;  167 1041-1045
  • 166 Casey M L, Cox S M, Beutler B, Milewich L, MacDonald P C. Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor.  J Clin Invest. 1989;  83 430-436
  • 167 Romero R, Mazor M, Manogue K, Oyarzun E, Cerami A. Human decidua: a source of cachectin-tumor necrosis factor.  Eur J Obstet Gynecol Reprod Biol. 1991;  41 123-127
  • 168 Romero R, Manogue K R, Mitchell M D et al.. Infection and labor. IV. Cachectin-tumor necrosis factor in the amniotic fluid of women with intraamniotic infection and preterm labor.  Am J Obstet Gynecol. 1989;  161 336-341
  • 169 Silver R M, Lohner S, Chen C L. Tumor necrosis factor-alpha mediates LPS-induced abortion: evidence from the LPS-resistant murine strain C3H/HeJ.  J Soc Gynecol Investig. 1993;  218 (Abst)
  • 170 Fidel Jr P L, Romero R, Cutright J et al.. Treatment with the interleukin-I receptor antagonist and soluble tumor necrosis factor receptor Fc fusion protein does not prevent endotoxin-induced preterm parturition in mice.  J Soc Gynecol Investig. 1997;  4 22-26
  • 171 Watari M, Watari H, DiSanto M E et al.. Pro-inflammatory cytokines induce expression of matrix-metabolizing enzymes in human cervical smooth muscle cells.  Am J Pathol. 1999;  154 1755-1762
  • 172 Fortunato S J, Menon R, Lombardi S J. Role of tumor necrosis factor-[alpha] in the premature rupture of membranes and preterm labor pathways.  Am J Obstet Gynecol. 2002;  187 1159-1162
  • 173 Athayde N, Edwin S S, Romero R et al.. A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes.  Am J Obstet Gynecol. 1998;  179 1248-1253
  • 174 Maymon E, Romero R, Pacora P et al.. Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection.  Am J Obstet Gynecol. 2000;  183 887-894
  • 175 Romero R, Chaiworapongsa T, Espinoza J et al.. Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes.  Am J Obstet Gynecol. 2002;  187 1125-1130
  • 176 Osmers R GW, Adelmann-Grill B C, Rath W et al.. Biochemical events in cervical ripening dilatation during pregnancy and parturition.  J Obstet Gynaecol. 1995;  21 185-194
  • 177 Rath W, Winkler M, Kemp B. The importance of extracellular matrix in the induction of preterm delivery.  J Perinat Med. 1998;  26 437-441
  • 178 Chwalisz K, Benson M, Scholz P et al.. Cervical ripening with the cytokines interleukin 8, interleukin 1[beta] and tumour necrosis factor [alpha] in guinea-pigs.  Hum Reprod. 1994;  9 2173-2181
  • 179 Romero R, Avila C, Santhanam U, Sehgal P B. Amniotic fluid interleukin 6 in preterm labor. Association with infection.  J Clin Invest. 1990;  85 1392-1400
  • 180 Cox S M, King M R, Casey M L, MacDonald P C. Interleukin-1 beta, -1 alpha, and -6 and prostaglandins in vaginal/cervical fluids of pregnant women before and during labor.  J Clin Endocrinol Metab. 1993;  77 805-815
  • 181 Gomez R, Romero R, Galasso M et al.. The value of amniotic fluid interleukin-6, white blood cell count, and gram stain in the diagnosis of microbial invasion of the amniotic cavity in patients at term.  Am J Reprod Immunol. 1994;  32 200-210
  • 182 Hillier S L, Witkin S S, Krohn M A et al.. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection.  Obstet Gynecol. 1993;  81 941-948
  • 183 Messer J, Eyer D, Donato L et al.. Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection.  J Pediatr. 1996;  129 574-580
  • 184 Hanna N, Hanna I, Hleb M et al.. Gestational age-dependent expression of IL-10 and its receptor in human placental tissues and isolated cytotrophoblasts.  J Immunol. 2000;  164 5721-5728
  • 185 Hanna N, Bonifacio L, Weinberger B et al.. Evidence for interleukin-10-mediated inhibition of cyclo-oxygenase-2 expression and prostaglandin production in preterm human placenta.  Am J Reprod Immunol. 2006;  55 19-27
  • 186 Athayde N, Romero R, Maymon E et al.. Interleukin 16 in pregnancy, parturition, rupture of fetal membranes, and microbial invasion of the amniotic cavity.  Am J Obstet Gynecol. 2000;  182 135-141
  • 187 Pacora P, Romero R, Maymon E et al.. Participation of the novel cytokine interleukin 18 in the host response to intra-amniotic infection.  Am J Obstet Gynecol. 2000;  183 1138-1143
  • 188 Saito S, Kato Y, Ishihara Y, Ichijo M. Amniotic fluid granulocyte colony-stimulating factor in preterm and term labor.  Clin Chim Acta. 1992;  208 105-109
  • 189 Saito S, Kasahara T, Kato Y, Ishihara Y, Ichijo M. Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition.  Cytokine. 1993;  5 81-88
  • 190 Goldenberg R L, Andrews W W, Mercer B M et al.. The preterm prediction study: granulocyte colony-stimulating factor and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.  Am J Obstet Gynecol. 2000;  182 625-630
  • 191 Chaiworapongsa T, Romero R, Espinoza J et al.. Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity.  J Matern Fetal Neonatal Med. 2005;  18 405-416
  • 192 Romero R, Ceska M, Avila C et al.. Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition.  Am J Obstet Gynecol. 1991;  165 813-820
  • 193 Yoon B H, Romero R, Jun J K et al.. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia.  Am J Obstet Gynecol. 1997;  177 825-830
  • 194 Ghezzi F, Gomez R, Romero R et al.. Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia.  Eur J Obstet Gynecol Reprod Biol. 1998;  78 5-10
  • 195 Esplin M S, Romero R, Chaiworapongsa T et al.. Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection.  J Matern Fetal Neonatal Med. 2005;  17 365-373
  • 196 Keelan J A, Yang J, Romero R J et al.. Epithelial cell-derived neutrophil-activating peptide-78 is present in fetal membranes and amniotic fluid at increased concentrations with intra-amniotic infection and preterm delivery.  Biol Reprod. 2004;  70 253-259
  • 197 Athayde N, Romero R, Maymon E et al.. A role for the novel cytokine RANTES in pregnancy and parturition.  Am J Obstet Gynecol. 1999;  181 989-994
  • 198 Hirsch E, Muhle R A, Mussalli G M, Blanchard R. Bacterially induced preterm labor in the mouse does not require maternal interleukin-1 signaling.  Am J Obstet Gynecol. 2002;  186 523-530
  • 199 Hirsch E, Filipovich Y. The IL-1 type I and the TNF type I receptors are essential mediators of bacterially induced preterm labor in a murine model.  J Soc Gynecol Investig. 2004;  11 327 (Abst)
  • 200 Terrone D A, Rinehart B K, Granger J P et al.. Interleukin-10 administration and bacterial endotoxin-induced preterm birth in a rat model.  Obstet Gynecol. 2001;  98 476-480
  • 201 Rodts-Palenik S, Wyatt-Ashmead J, Pang Y et al.. Maternal infection-induced white matter injury is reduced by treatment with interleukin-10.  Am J Obstet Gynecol. 2004;  191 1387-1392
  • 202 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference . Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.  Crit Care Med. 1992;  20 864-874
  • 203 Weiss M, Moldawer L L, Schneider E M. Granulocyte colony-stimulating factor to prevent the progression of systemic nonresponsiveness in systemic inflammatory response syndrome and sepsis.  Blood. 1999;  93 425-439
  • 204 Levy M M, Fink M P, Marshall J C et al.. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.  Intensive Care Med. 2003;  29 530-538
  • 205 Gomez R, Ghezzi F, Romero R et al.. Two thirds of human fetuses with microbial invasion of the amniotic cavity have a detectable systemic cytokine response before birth.  Am J Obstet Gynecol. 1997;  176 S14
  • 206 Yoon B H, Romero R, Kim K S et al.. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia.  Am J Obstet Gynecol. 1999;  181 773-779
  • 207 Chaiworapongsa T, Romero R, Kim J C et al.. Evidence for fetal involvement in the pathologic process of clinical chorioamnionitis.  Am J Obstet Gynecol. 2002;  186 1178-1182
  • 208 Witt A, Berger A, Gruber C J et al.. IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity.  J Perinat Med. 2005;  33 22-26
  • 209 Pacora P, Chaiworapongsa T, Maymon E et al.. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome.  J Matern Fetal Neonatal Med. 2002;  11 18-25
  • 210 D'Alquen D, Kramer B W, Seidenspinner S et al.. Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis.  Pediatr Res. 2005;  57 263-269
  • 211 Yoon B H, Romero R, Park J S et al.. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years.  Am J Obstet Gynecol. 2000;  182 675-681
  • 212 Yoon B H, Romero R, Shim J Y et al.. C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis.  J Matern Fetal Neonatal Med. 2003;  14 85-90
  • 213 Sampson J E, Theve R P, Blatman R N et al.. Fetal origin of amniotic fluid polymorphonuclear leukocytes.  Am J Obstet Gynecol. 1997;  176 77-81
  • 214 Shim S S, Yoon B H, Romero R et al.. The frequency and clinical significance on intra-amniotic inflammation in patients with preterm premature rupture of the membranes.  Am J Obstet Gynecol. 2003;  189 S83
  • 215 Romero R, Athayde N, Gomez R et al.. The fetal inflammatory response syndrome is characterized by the outpouring of a potent extracellular matrix degrading enzyme into the fetal circulation.  Am J Obstet Gynecol. 1998;  178 S3
  • 216 Gomez R, Berry S, Yoon B H et al.. The hematologic profile of the fetus with systemic inflammatory response syndrome.  Am J Obstet Gynecol. 1998;  178 S202
  • 217 Berry S M, Gomez R, Athayde N et al.. The role of granulocyte colony stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome.  Am J Obstet Gynecol. 1998;  178 S202
  • 218 Gomez R, Romero R, Ghezzi F et al.. Are fetal hypoxia and acidemia causes of preterm labor and delivery?.  Am J Obstet Gynecol. 1997;  176 S115
  • 219 Baschat A A, Gembruch U, Reiss I et al.. Neonatal nucleated red blood cell counts in growth-restricted fetuses: relationship to arterial and venous Doppler studies.  Am J Obstet Gynecol. 1999;  181 190-195
  • 220 Ferber A, Minior V K, Bornstein E, Divon M Y. Fetal “nonreassuring status” is associated with elevation of nucleated red blood cell counts and interleukin-6.  Am J Obstet Gynecol. 2005;  192 1427-1429
  • 221 Berry S M, Romero R, Gomez R et al.. Premature parturition is characterized by in utero activation of the fetal immune system.  Am J Obstet Gynecol. 1995;  173 1315-1320
  • 222 Di Naro E, Cromi A, Ghezzi F et al.. Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome.  Am J Obstet Gynecol. 2006;  194 153-159
  • 223 Haeryfar S M, Berczi I. The thymus and the acute phase response.  Cell Mol Biol. 2001;  47 145-156
  • 224 Yoon B H, Romero R, Jun J K et al.. An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes.  Am J Obstet Gynecol. 1998;  179 1107-1114
  • 225 Dolecek R. Endocrine changes after burn trauma-a review.  Keio J Med. 1989;  38 262-276
  • 226 Seckl J R, Cleasby M, Nyirenda M J. Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming.  Kidney Int. 2000;  57 1412-1417
  • 227 Dodic M, Hantzis V, Duncan J et al.. Programming effects of short prenatal exposure to cortisol.  FASEB J. 2002;  16 1017-1026
  • 228 Nathanielsz P W, Berghorn K A, Derks J B et al.. Life before birth: effects of cortisol on future cardiovascular and metabolic function.  Acta Paediatr. 2003;  92 766-772
  • 229 Seckl J R, Meaney M J. Glucocorticoid programming.  Ann N Y Acad Sci. 2004;  1032 63-84
  • 230 Kim Y M, Kim G J, Kim M R et al.. Skin: an active component of the fetal innate immune system.  Am J Obstet Gynecol. 2003;  189 S74
  • 231 Yoon B H, Kim Y A, Romero R et al.. Association of oligohydramnios in women with preterm premature rupture of membranes with an inflammatory response in fetal, amniotic, and maternal compartments.  Am J Obstet Gynecol. 1999;  181 784-788
  • 232 Heine R P, Wiesenfeld H, Mortimer L, Greig P C. Amniotic fluid defensins: potential markers of subclinical intrauterine infection.  Clin Infect Dis. 1998;  27 513-518
  • 233 Espinoza J, Chaiworapongsa T, Romero R et al.. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes.  J Matern Fetal Neonatal Med. 2003;  13 2-21
  • 234 Romero R, Espinoza J, Goncalves L F et al.. Fetal cardiac dysfunction in preterm premature rupture of membranes.  J Matern Fetal Neonatal Med. 2004;  16 146-157
  • 235 Court O, Kumar A, Parrillo J E, Kumar A. Clinical review: myocardial depression in sepsis and septic shock.  Crit Care. 2002;  6 500-508
  • 236 Kumar A, Krieger A, Symeoneides S, Kumar A, Parrillo J E. Myocardial dysfunction in septic shock: Part II Role of cytokines and nitric oxide.  J Cardiothorac Vasc Anesth. 2001;  15 485-511
  • 237 Kumar A, Haery C, Parrillo J E. Myocardial dysfunction in septic shock: Part I Clinical manifestation of cardiovascular dysfunction.  J Cardiothorac Vasc Anesth. 2001;  15 364-376
  • 238 Yanowitz T D, Jordan J A, Gilmour C H et al.. Hemodynamic disturbances in premature infants born after chorioamnionitis: association with cord blood cytokine concentrations.  Pediatr Res. 2002;  51 310-316
  • 239 Garnier Y, Coumans A B, Jensen A, Hasaart T H, Berger R. Infection-related perinatal brain injury: the pathogenic role of impaired fetal cardiovascular control.  J Soc Gynecol Investig. 2003;  10 450-459
  • 240 Kaukola T, Herva R, Perhomaa M et al.. Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants.  Pediatr Res. 2006;  59 478-483
  • 241 Lahra M M, Jeffery H E. A fetal response to chorioamnionitis is associated with early survival after preterm birth.  Am J Obstet Gynecol. 2004;  190 147-151
  • 242 Yoon B H, Romero R, Shim J Y et al.. “Atypical” chronic lung disease of the newborn is linked to fetal systemic inflammation.  Am J Obstet Gynecol. 2002;  187 S129
  • 243 Jobe A H. Antenatal factors and the development of bronchopulmonary dysplasia.  Semin Neonatol. 2003;  8 9-17
  • 244 Dammann O, Allred E N, Van Marter L J, Dammann C E, Leviton A. Bronchopulmonary dysplasia is not associated with ultrasound-defined cerebral white matter damage in preterm newborns.  Pediatr Res. 2004;  55 319-325
  • 245 Dammann O, Leviton A, Bartels D B, Dammann C E. Lung and brain damage in preterm newborns. Are they related? How? Why?.  Biol Neonate. 2004;  85 305-313
  • 246 Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn.  Pediatr Res. 1997;  42 1-8
  • 247 Yoon B H, Romero R, Kim C J et al.. High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia.  Am J Obstet Gynecol. 1997;  177 406-411
  • 248 Leviton A, Dammann O, Durum S K. The adaptive immune response in neonatal cerebral white matter damage.  Ann Neurol. 2005;  58 821-828
  • 249 Bashiri A, Burstein E, Mazor M. Cerebral palsy and fetal inflammatory response syndrome: a review.  J Perinat Med. 2006;  34 5-12
  • 250 Christensen K K. Infection as a predominant cause of perinatal mortality.  Obstet Gynecol. 1982;  59 499-508
  • 251 Christensen K K, Christensen P, Hagerstrand I et al.. The clinical significance of group B streptococci.  J Perinat Med. 1982;  10 133-146
  • 252 Tafari N, Ross S, Naeye R L, Judge D M, Marboe C. Mycoplasma T strains and perinatal death.  Lancet. 1976;  1 108-109
  • 253 Blackwell S, Romero R, Chaiworapongsa T et al.. Maternal and fetal inflammatory responses in unexplained fetal death.  J Matern Fetal Neonatal Med. 2003;  14 151-157
  • 254 Gerber S, Yih M, Vardhana S et al.. Relation between fetal interleukin-1 receptor antagonist (IL-1RA) gene polymorphism and unexplained fetal death.  Am J Obstet Gynecol. 2002;  187 S58
  • 255 Witkin S S, Gerber S, Ledger W J. Influence of interleukin-1 receptor antagonist gene polymorphism on disease.  Clin Infect Dis. 2002;  34 204-209
  • 256 Vamvakopoulos J, Green C, Metcalfe S. Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist.  Eur J Immunol. 2002;  32 2988-2996
  • 257 Romero R, Mazor M, Brandt F et al.. Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition.  Am J Reprod Immunol. 1992;  27 117-123
  • 258 Naccasha N, Gervasi M T, Chaiworapongsa T et al.. Phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and maternal infection.  Am J Obstet Gynecol. 2001;  185 1118-1123
  • 259 Gervasi M T, Chaiworapongsa T, Naccasha N et al.. Phenotypic and metabolic characteristics of maternal monocytes and granulocytes in preterm labor with intact membranes.  Am J Obstet Gynecol. 2001;  185 1124-1129
  • 260 Gervasi M T, Chaiworapongsa T, Naccasha N et al.. Maternal intravascular inflammation in preterm premature rupture of membranes.  J Matern Fetal Neonatal Med. 2002;  11 171-175

Roberto RomeroM.D. 

Perinatology Research Branch, NICHD/NIH/DHHS Hutzel Women's Hospital - Box #4

3990 John R., Detroit, MI 48201

eMail: warfiela@mail.nih.gov