OBJECTIVE: To characterize subgroups of preterm prelabor rupture of membranes (PPROM) and short-term neonatal outcomes based on the presence and absence of intraamniotic inflammation (IAI) and/or microbial invasion of the amniotic cavity (MIAC). METHODS: One hundred and sixty-six Caucasian women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis (n=166) and were assayed for interleukin-6 levels by a lateral flow immunoassay. The presence of Ureaplasma species, Mycoplasma hominis, Chlamydia trachomatis, and 16S rRNA was evaluated in the amniotic fluid. IAI was defined as amniotic fluid IL-6 values, measured by a point of care test, higher than 745 pg/mL. RESULTS: Microbial-associated IAI (IAI with MIAC) and sterile intraamniotic inflammation (IAI alone) were found in 21% and 4%, respectively, of women with PPROM. Women with microbial-associated IAI had higher microbial loads of Ureaplasma species in the amniotic fluid than women with MIAC alone. No differences in the short-term neonatal morbidity with respect to the presence of microbial-associated IAI, sterile IAI and MIAC alone were found after adjusting for the gestational age at delivery in women with PPROM. CONCLUSIONS: Microbial-associated but not sterile intraamniotic inflammation is common in Caucasian women with PPROM. The gestational age at delivery but not the presence of inflammation affects the short-term neonatal morbidity of newborns from PPROM pregnancies.

Department of Genes and Environment Division of Epidemiology Norwegian Institute of Public Health Oslo Norway; Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine and Perinatal Research The University of Texas Medical Branch at Galveston Galveston Texas United States of America

Department of Obstetrics and Gynecology Charles University Prague Faculty of Medicine Hradec Kralove University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Obstetrics and Gynecology Charles University Prague Faculty of Medicine Hradec Kralove University Hospital Hradec Kralove Hradec Kralove Czech Republic; Biomedical Research Center University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Obstetrics and Gynecology Sahlgrenska Academy Gothenburg Sweden

Institute of Clinical Biochemistry University Hospital Hradec Kralove Hradec Kralove Czech Republic

Zobrazit více v PubMed

Menon R, Boldogh I, Hawkins HK, Woodson M, Polettini J, Syed TA, et al. (2014) Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro. Am J Pathol 184: 1740–1751. 10.1016/j.ajpath.2014.02.011 PubMed DOI

Menon R, Polettini J, Syed TA, Saade GR, Boldogh I (2014) Expression of 8-oxoguanine glycosylase in human fetal membranes. Am J Reprod Immunol 72: 75–84. 10.1111/aji.12220 PubMed DOI

Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z, et al. (2014) Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med: 1–16. PubMed PMC

Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S (2007) The role of inflammation and infection in preterm birth. Semin Reprod Med 25: 21–39. PubMed PMC

Bredeson S, Papaconstantinou J, Difford JH, Kechichian T, Syed TA, Saade GR, et al. (2014) HMGB1 Promotes a p38MAPK Associated Non-Infectious Inflammatory Response Pathway in Human Fetal Membranes. PLoS One 9: e113799 10.1371/journal.pone.0113799 PubMed DOI PMC

Menon R, Taylor RN, Fortunato SJ (2010) Chorioamnionitis—a complex pathophysiologic syndrome. Placenta 31: 113–120. 10.1016/j.placenta.2009.11.012 PubMed DOI

Menon R (2014) Oxidative stress damage as a detrimental factor in preterm birth pathology. Front Immunol 5:567 10.3389/fimmu.2014.00567 PubMed DOI PMC

Kacerovsky M, Musilova I, Khatibi A, Skogstrand K, Hougaard DM, Tambor V, et al. (2012) Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 25: 2014–2019. 10.3109/14767058.2012.671873 PubMed DOI

Jacobsson B, Mattsby-Baltzer I, Andersch B, Bokstrom H, Holst RM, Nikolaitchouk N, et al. (2003) Microbial invasion and cytokine response in amniotic fluid in a Swedish population of women with preterm prelabor rupture of membranes. Acta Obstet Gynecol Scand 82: 423–431. PubMed

DiGiulio DB, Romero R, Kusanovic JP, Gomez R, Kim CJ, Seok KS, et al. (2010) Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 64: 38–57. 10.1111/j.1600-0897.2010.00830.x PubMed DOI PMC

Romero R, Ghidini A, Mazor M, Behnke E (1991) Microbial invasion of the amniotic cavity in premature rupture of membranes. Clin Obstet Gynecol 34: 769–778. PubMed

Kacerovsky M, Pliskova L, Bolehovska R, Skogstrand K, Hougaard DM, Tsiartas P, et al. (2012) The impact of the microbial load of genital mycoplasmas and gestational age on the intensity of intraamniotic inflammation. Am J Obstet Gynecol 206: 342 e341–348. PubMed

Kacerovsky M, Pliskova L, Bolehovska R, Musilova I, Hornychova H, Tambor V, et al. (2011) The microbial load with genital mycoplasmas correlates with the degree of histologic chorioamnionitis in preterm PROM. Am J Obstet Gynecol 205: 213 e211–217. PubMed

Jacobsson B, Aaltonen R, Rantakokko-Jalava K, Morken NH, Alanen A (2009) Quantification of Ureaplasma urealyticum DNA in the amniotic fluid from patients in PTL and pPROM and its relation to inflammatory cytokine levels. Acta Obstet Gynecol Scand 88: 63–70. 10.1080/00016340802572646 PubMed DOI

Combs CA, Gravett M, Garite TJ, Hickok DE, Lapidus J, Porreco R, et al. (2014) Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol 210: 125 e121–125 e115. PubMed

Romero R, Chaiworapongsa T, Alpay Savasan Z, Xu Y, Hussein Y, Dong Z, et al. (2011) Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1. J Matern Fetal Neonatal Med 24: 1444–1455. 10.3109/14767058.2011.591460 PubMed DOI PMC

Kacerovsky M, Celec P, Vlkova B, Skogstrand K, Hougaard DM, Cobo T, et al. (2013) Amniotic fluid protein profiles of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria. PLoS One 8: e60399 10.1371/journal.pone.0060399 PubMed DOI PMC

Menon R, Williams SM, Fortunato SJ (2007) Amniotic fluid interleukin-1beta and interleukin-8 concentrations: racial disparity in preterm birth. Reprod Sci 14: 253–259. PubMed

Fortunato SJ, Lombardi SJ, Menon R (2004) Racial disparity in membrane response to infectious stimuli: a possible explanation for observed differences in the incidence of prematurity. Am J Obstet Gynecol 190: 1557–1562. PubMed

Romero R, Yoon BH, Kenney JS, Gomez R, Allison AC, Sehgal PB (1993) Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor. Am J Reprod Immunol 30: 167–183. PubMed

Romero R, Yoon BH, Mazor M, Gomez R, Gonzalez R, Diamond PB, et al. (1993) 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 169: 839–851. PubMed

Romero R, Kadar N, Miranda J, Korzeniewski SJ, Schwartz AG, Chaemsaithong P, et al. (2014) The diagnostic performance of the Mass Restricted (MR) score in the identification of microbial invasion of the amniotic cavity or intra-amniotic inflammation is not superior to amniotic fluid interleukin-6. J Matern Fetal Neonatal Med 27: 757–769. 10.3109/14767058.2013.844123 PubMed DOI PMC

Chaemsaithong P, Romero R, Korzeniewski SJ, Dong Z, Yeo L, Hassan SS, et al. (2014) A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10. J Matern Fetal Neonatal Med: 1–10. PubMed PMC

Chaemsaithong P, Romero R, Korzeniewski SJ, Martinez-Varea A, Dong Z, Yoon BH, et al. (2015) A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection. J Matern Fetal Neonatal Med: 1–8. PubMed PMC

Chaemsaithong P, Romero R, Korzeniewski SJ, Martinez-Varea A, Dong Z, Yoon BH, et al. (2015) A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes. J Matern Fetal Neonatal Med: 1–11. PubMed PMC

Kacerovsky M, Musilova I, Stepan M, Andrys C, Drahosova M, Jacobsson B (2015) Detection of intraamniotic inflammation in fresh and processed amniotic fluid samples with the interleukin-6 point of care test. Am J Obstet Gynecol 10.1016/j.ajog.2015.05.039 PubMed DOI

Greisen K, Loeffelholz M, Purohit A, Leong D (1994) PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J Clin Microbiol 32: 335–351. PubMed PMC

Fouhy F, Deane J, Rea MC, O'Sullivan O, Ross RP, O'Callaghan G, et al. (2015) The effects of freezing on faecal microbiota as determined using MiSeq sequencing and culture-based investigations. PLoS One 10: e0119355 10.1371/journal.pone.0119355 PubMed DOI PMC

Salafia CM, Weigl C, Silberman L (1989) The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. Obstet Gynecol 73: 383–389. PubMed

Papile LA, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92: 529–534. PubMed

Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM (1998) The fetal inflammatory response syndrome. Am J Obstet Gynecol 179: 194–202. PubMed

Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH (2009) The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications. Placenta 30: 56–61. 10.1016/j.placenta.2008.09.017 PubMed DOI PMC

Kacerovsky M, Musilova I, Hornychova H, Kutova R, Pliskova L, Kostal M, et al. (2014) Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes. Am J Obstet Gynecol 211: 385 e381–389. PubMed

Frenette P, Dodds L, Armson BA, Jangaard K (2013) Preterm prelabour rupture of membranes: effect of latency on neonatal and maternal outcomes. J Obstet Gynaecol Can 35: 710–717. PubMed

Nayot D, Penava D, Da Silva O, Richardson BS, de Vrijer B (2012) Neonatal outcomes are associated with latency after preterm premature rupture of membranes. J Perinatol 32: 970–977. 10.1038/jp.2012.15 PubMed DOI

Quantification of intra-amniotic inflammation in late preterm prelabour rupture of membranes

Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation

Development of a Rat Model of Intra-Amniotic Inflammation via Ultrasound-Guided Administration of a Triggering Agent in the Gestational Sac to Enable Analysis of Individual Amniotic Fluid Samples

Prevalence and Load of Cervical Ureaplasma Species With Respect to Intra-amniotic Complications in Women With Preterm Prelabor Rupture of Membranes Before 34 weeks

Clinical characteristics of colonization of the amniotic cavity in women with preterm prelabor rupture of membranes, a retrospective study

Acute Histological Chorioamnionitis and Birth Weight in Pregnancies With Preterm Prelabor Rupture of Membranes: A Retrospective Cohort Study

Presence of Chlamydia trachomatis DNA in the amniotic fluid in women with preterm prelabor rupture of membranes

IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study

Cervical Gardnerella vaginalis in women with preterm prelabor rupture of membranes

Comprehensive proteomic investigation of infectious and inflammatory changes in late preterm prelabour rupture of membranes

Antibiotic administration reduces the rate of intraamniotic inflammation in preterm prelabor rupture of the membranes

Late preterm prelabor rupture of fetal membranes: fetal inflammatory response and neonatal outcome

Maternal white blood cell count cannot identify the presence of microbial invasion of the amniotic cavity or intra-amniotic inflammation in women with preterm prelabor rupture of membranes

Expression profile of C19MC microRNAs in placental tissue of patients with preterm prelabor rupture of membranes and spontaneous preterm birth

Maternal serum C-reactive protein concentration and intra-amniotic inflammation in women with preterm prelabor rupture of membranes