Full length article| Volume 228, P13-26, September 2018

Download started.


Validation of diagnostic tests for histologic chorioamnionitis: Systematic review and meta-analysis



      The aim of this study was to determine the diagnostic performance of different diagnostic tests for histologic chorioamnionitis in patients at more than 20 weeks of gestation.


      A systematic search was carried out through MEDLINE, EMBASE, LILACS, CENTRAL and unpublished literature. Observational studies included with pregnant women (>20 weeks) with chorioamnionitis. The reference standard was the histopathological study of the placenta, umbilical cord and fetal membranes. Two independent researchers extracted data and performed a meta-analysis of diagnostic tests.


      Twenty-nine articles were included. The studies provided evidence in the form of maternal clinical and serological tests; tests of vaginal fluid, amniotic fluid or the umbilical cord; fetal monitoring and ultrasound tests. To assess the performance of maternal serum CRP, 13 studies were included, showing a combined sensitivity of 68.7% (95%CI 58%–77%) and a combined specificity of 77.1% (95%CI 67%–84%). Maternal leukocytosis was evaluated in four publications, showing a combined sensitivity of 51% (95%CI 40%–62%) and a combined specificity of 65% (95%CI 50%–78%).


      CRP and maternal leukocytosis, showed a low sensitivity and specificity. The sonographic evaluation of the fetal thymus is also more sensitive for the diagnosis of histologic chorioamnionitis than the fetal biophysical profile.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Petit E.
        • Abergel A.
        • Dedet B.
        • Subtil D.
        Prématurité et infection: état des connaissances.
        J Gynecol Obstet Biol la Reprod Elsevier Masson SAS. 2012; 41: 14-25
        • Romero R.
        • Miranda J.
        • Kusanovic J.
        Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques.
        J Perinat Med. 2015; 43: 19-36
        • Redline R.
        • Faye-Petersen O.
        • Heller D.
        Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns.
        Pediatr Dev Pathol. 2003; 6: 435-438
        • González-buitrago J.
        • Ferreira L.
        • Muñiz C.
        Proteómica clínica y nuevos biomarcadores en los líquidos biológicos.
        Med Clin. 2008; 131: 426-434
        • Locksmith G.J.
        • Clark P.
        • Duff P.
        • Saade G.R.
        • Schultz G.S.
        Amniotic fluid concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 during pregnancy and labor.
        Am J Obstet Gynecol. 2001; 184: 159-164
        • Królak-Olejnik B.
        • Kaźmierczak W.
        • Olejnik I.
        Amniotic fluid analysis. Part I: rapid markers in the prediction of intra-amniotic infection.
        Ginekol Pol. 2005; 76: 77-84
        • Deeks J.
        • Wisniewski S.
        • Davenport C.
        Guide to the contents of a cochrane diagnostic test accuracy protocol.
        Cochrane handbook for systematic reviews of diagnostic test accuracy version 100. 2013: 1-15
        • Loke Y.K.
        • Price D.
        • Herxheimer A.
        Systematic reviews of adverse effects: framework for a structured approach.
        BMC Med Res Methodol. 2007; 7 ([Internet]. Jan [cited 2013 Dec 26], Available from:): 32
        • González Rodríguez M.
        • Velarde Mayol C.
        Fundamentos de medicina basada en la evidencia: Listas guía de comprobación de estudios sobre pruebas diagnósticas incluidos en las revisiones sistemáticas: declaración QUADAS.
        Evid Pediatr. 2012; 8: 1-6
        • Higgins J.
        • Green S.
        Cochrane handbook for systematic reviews of interventions version 5.1.0.
        ([Internet] Available from:) The Cochrane Collaboration, 2011
        • Leeflang M.M.G.
        • Deeks J.J.
        • Takwoingi Y.
        • Macaskill P.
        Cochrane diagnostic test accuracy reviews.
        Syst Rev Syst Rev. 2013; 2: 82
        • Higgins J.
        • Thompson S.
        • Deeks J.
        • Altman D.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Oludag T.
        • Gode F.
        • Caglayan E.
        • Saatli B.
        • Okyay R.E.
        • Altunyurt S.
        Value of maternal procalcitonin levels for predicting subclinical intra-amniotic infection in preterm premature rupture of membranes | read by QxMD.
        J Obstet Gynaecol Res. 2014; 40: 954-960
        • Shimoya K.
        • Matsuzaki N.
        • Taniguchi T.
        • Okada T.
        • Saji F.
        • Murata Y.
        Interleukin-8 level in maternal serum as a marker for screening of histological chorioamnionitis at term.
        Int J Gynecol Obstet. 1997; 57: 153-159
        • M a Kim
        • Lee Y.S.
        • Seo K.
        Assessment of predictive markers for placental inflammatory response in preterm births.
        PLoS One. 2014; 9
        • Skrablin S.
        • Lovric H.
        • Banovic V.
        • Kralik S.
        • Dijakovic A.
        • Kalafatic D.
        Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery.
        J Matern Fetal Neonatal Med. 2007; 20: 335-341
        • Ismail M.A.
        • Zinaman M.J.
        • Lowensohn R.I.
        Moawad a H. The significance of C-reactive protein levels in women with premature rupture of membranes.
        Am J Obstet Gynecol. 1985; 151: 541-544
        • Steinborn A.
        • Sohn C.
        • Scharf A.
        • Geka F.
        • Heger S.
        • Kaufmann M.
        Serum intercellular adhesion molecule-1 levels and histologic chorioamnionitis.
        Obstet Gynecol. 2000; 95: 671-676
        • Yoon B.H.
        • Romero R.
        • Kim C.J.
        • Jun J.K.
        • Gomez R.
        • Choi J.H.
        • et al.
        Amniotic fluid interleukin-6: a sensitive test for antenatal diagnosis of acute inflammatory lesions of preterm placenta and prediction of perinatal morbidity.
        Am J Obstet Gynecol. 1995; 172: 960-970
        • Popowski T.
        • Goffinet F.
        • Maillard F.
        • Schmitz T.
        • Leroy S.
        • Kayem G.
        Maternal markers for detecting early-onset neonatal infection and chorioamnionitis in cases of premature rupture of membranes at or after 34 weeks of gestation: a two-center prospective study.
        BMC Pregnancy Childbirth BioMed Central Ltd. 2011; 11: 1-9
        • Yoneda S.
        • Shiozaki A.
        • Ito M.
        • Yoneda N.
        • Inada K.
        • Yonezawa R.
        • et al.
        Accurate prediction of the stage of histological chorioamnionitis before delivery by amniotic fluid IL-8 level.
        Am J Reprod Immunol. 2015; 73: 568-576
        • Curtin W.M.
        • Katzman P.J.
        • Florescue H.
        • Metlay L.A.
        Accuracy of signs of clinical chorioamnionitis in the term parturient.
        J Perinatol Nat Publ Group. 2013; 33: 422-428
        • Tasci Y.
        • Dilbaz B.
        • Uzmez Onal B.
        • Caliskan E.
        • Dilbaz S.
        • Doganci L.
        • et al.
        The value of cord blood interleukin-6 levels for predicting chorioamnionitis, funisitis and neonatal infection in term premature rupture of membranes.
        Eur J Obstet Gynecol Reprod Biol. 2006; 128: 34-39
        • Thornburg L.L.
        • Queenan R.
        • Brandt-griffith B.
        • Pressman E.K.
        Procalcitonin for prediction of chorioamnionitis in preterm premature rupture of membranes procalcitonin for prediction of chorioamnionitis in preterm premature rupture of membranes.
        J Matern Neonatal Med. 2016; 29: 2056-2061
        • Park C.W.
        • Mi Lee S.
        • Shin Park J.
        • Kwan Jun J.
        • Romero R.
        • Yoon B.H.
        The antenatal identification of funisitis with a rapid MMP-8 bedside test.
        J Perinat Med. 2008; 36: 497-502
        • Cobo T.
        • Kacerovsky M.
        • Palacio M.
        • Hornychova H.
        • Hougaard D.M.
        • Skogstrand K.
        • et al.
        A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.
        J Matern Fetal Neonatal Med. 2012; 25: 1995-2001
        • Canzoneri B.
        • Grotegut C.
        • Swamy G.
        • Brancazio L.
        • Sinclair T.
        • Heine P.
        • et al.
        Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics.
        J Matern Neonatal Med. 2012; 25: 1329-1332
        • Grable I.A.
        • Heine R.P.
        Neutrophil granule products: can they identify subclinical chorioamnionitis in patients with preterm premature rupture of membranes?.
        Am J Obstet Gynecol. 2003; 189: 808-812
        • Ghidini A.
        • Salafia C.M.
        • Kirn V.
        • Doria V.
        • Spong C.Y.
        Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks.
        Obstet Gynecol. 2000; 96: 201-206
        • Odibo A.O.
        • Rodis J.F.
        • Sanders M.M.
        • Borgida A.F.
        • Wilson M.
        • Egan J.F.
        • et al.
        Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes.
        J Perinatol. 1999; 19: 407-412
        • Sherer D.M.
        • Spong C.Y.
        • Salafia C.M.
        Fetal breathing movements within 24 h of delivery in prematurity are related to histologic and clinical evidence of amnionitis.
        Am J Perinatol. 1997; 14: 337-340
        • Cherouny P.H.
        • Pankuch G.A.
        • Romero R.
        • Botti J.J.
        • Kuhn D.C.
        • Demers L.M.
        • et al.
        Neutrophil attractant/activating peptide-1/interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants.
        Am J Obstet Gynecol. 1993; 169: 1299-1303
        • Kacerovsky M.
        • Musilova I.
        • Hornychova H.
        • Kutova R.
        • Pliskova L.
        • Kostal M.
        • et al.
        Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes.
        Am J Obstet Gynecol. 2014; 211 (Elsevier Inc., e1-385.e9): 385
        • Aksakal S.
        • Kandemir O.
        • Altinbas S.
        • Esin S.
        • Muftuoglu K.
        Fetal tyhmus size as a predictor of histological chorioamnionitis in preterm premature rupture of membranes.
        J Matern Fetal Neonatal Med. 2014; 27: 1118-1122
        • Musilova I.
        • Hornychova H.
        • Kostal M.
        • Jacobsson B.
        • Kacerovsky M.
        Ultrasound measurement of the transverse diameter of the fetal thymus in pregnancies complicated by the preterm prelabor rupture of membranes.
        J Clin Ultrasound. 2013; 41: 283-289
        • Amirabi A.
        • Naji S.
        • Yekta Z.
        • Sadeghi Y.
        Chorioamnionitis and diagnostic value of C-reactive protein, erythrocyte sedimentation rate and white blood cell count in its diagnosis among pregnant women with premature rupture of membranes.
        Pak J Biol Sci. 2012; 15: 454-458
        • Perrone G.
        • Anceschi M.M.
        • Capri O.
        • Galoppi P.
        • Pizzulo S.
        • Buccheri M.
        • et al.
        Maternal C-reactive protein at hospital admission is a simple predictor of funisitis in preterm premature rupture of membranes.
        Gynecol Obstet Invest. 2012; 74: 95-99
        • Lee S.Y.
        • Park K.H.
        • Jeong E.H.
        • Oh K.J.
        • Ryu A.
        • Park K.U.
        Relationship between maternal serum C-reactive protein, funisitis and early-onset neonatal sepsis.
        J Korean Med Sci. 2012; 27: 674-680
        • Oh K.J.
        • Park K.H.
        • Kim S.N.
        • Jeong E.H.
        • Lee S.Y.
        • Yoon H.Y.
        Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta.
        Placenta. 2011; 32: 732-736
        • Pacora P.
        • Chaiworapongsa T.
        • Maymon E.
        • Kim Y.M.
        • Gomez R.
        • Yoon B.H.
        • et al.
        Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome.
        J Matern Fetal Neonatal Med. 2002; 11: 18-25
        • Fisk N.M.
        • Fysh J.
        • Child A.G.
        • Gatenby P.A.
        • Jeffery H.
        • Bradfield A.H.
        • et al.
        Is C-reactive protein really useful in preterm premature rupture of the membranes?.
        Br J Obstet Gynaecol. 1987; 94: 1159-1164
        • Yinon Y.
        • Zalel Y.
        • Weisz B.
        • Mazaki-Tovi S.
        • Sivan E.
        • Schiff E.
        • et al.
        Fetal thymus size as a predictor of chorioamnionitis in women with preterm premature rupture of membranes.
        Ultrasound Obstet Gynecol. 2007; 29: 639-643
        • Park H.S.
        • Kim S.A.
        The value of the genedia MMP-8 rapid test for diagnosing intraamniotic infection/inflammation and predicting adverse pregnancy outcomes in women with preterm premature rupture of membranes.
        Am J Obstet Gynecol. 2015; 212 (Elsevier Inc.): S174
        • Brandt-Griffith B.
        • Pressman E.
        • Thornburg L.
        Procalcitonin for assessment of chorioamniotis in preterm premature rupture of membranes.
        Am J Obstet Gynecol. 2011; 204 (Elsevier Inc.): S187
        • Romero R.
        • Yoon B.H.
        • Mazor M.
        • Gomez R.
        • Gonzalez R.
        • Diamond M.P.
        • et al.
        A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes.
        Am J Obstet Gynecol. 1993; 169: 839-851