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Intra-Amniotic Infection

Tarja Myntti, Leena Rahkonen, Irmeli Nupponen, Anu Pätäri-Sampo, Minna Tikkanen, Timo Sorsa, Juuso Juhila, Sture Andersson, Jorma Paavonen, Vedran Stefanovic
Introduction. Intra-amniotic infection (IAI) is a major cause of preterm labor and adverse neonatal outcome. We evaluated amniotic fluid (AF) proteolytic cascade forming biomarkers in relation to microbial invasion of the amniotic cavity (MIAC) and IAI in preterm pregnancies with intact membranes. Material and Methods. Amniocentesis was made to 73 women with singleton pregnancies; 27 with suspected IAI; and 46 controls. AF biomarkers were divided into three cascades: Cascade 1: matrix metalloproteinase-8 (MMP-8), MMP-9, myeloperoxidase (MPO), and interleukin-6; Cascade 2: neutrophil elastase (HNE), elafin, and MMP-9; Cascade 3: MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP)...
2017: Disease Markers
Nardhy Gomez-Lopez, Roberto Romero, Marcia Arenas-Hernandez, Bogdan Panaitescu, Valeria Garcia-Flores, Tara N Mial, Aashna Sahi, Sonia S Hassan
OBJECTIVE: Intra-amniotic infection is associated with spontaneous preterm labor. In most cases, the infection is subclinical and bacteria are detected in the amniotic cavity rather than in the chorioamniotic membranes. The aims of this study were to determine whether the intra-amniotic injection of a microbial product, lipopolysaccharide (LPS), could induce preterm labor/birth, and to compare this model to two established models of LPS-induced preterm labor/birth. METHODS: Pregnant B6 mice received an intra-amniotic, intra-uterine, or intra-peritoneal injection of LPS (100 ng/amniotic sac, 15μg/25μL, and 15μg/200μL respectively) or PBS (control)...
January 31, 2017: Journal of Maternal-fetal & Neonatal Medicine
Rauf Melekoglu, Osman Ciftci, Sevil Eraslan, Nese Basak, Ebru Celik
AIM: The aim of this study was to determine the effects of obesity on amniotic fluid (AF) inflammatory markers in second-trimester AF, testing the hypothesis that there is a relationship between maternal body mass index (BMI) and fetal inflammatory exposure. METHODS: AF was obtained from 84 singleton pregnant women undergoing elective amniocentesis for karyotype analysis at 16-24 weeks of gestation between April 2014 and May 2016. The cell-free AF was used to analyze interleukin (IL)-1β and IL-6, and matrix metalloproteinase (MMP)-1, MMP-6, and MMP-13...
January 20, 2017: Gynecologic and Obstetric Investigation
Nardhy Gomez-Lopez, Roberto Romero, Yaozhu Leng, Valeria Garcia-Flores, Yi Xu, Derek Miller, Sonia S Hassan
PROBLEM: Neutrophil extracellular traps (NETs) were recently described as a mechanism for microbial killing in the amniotic cavity of women with intra-amniotic infection. Such a clinical condition can result in acute chorioamnionitis, a placental lesion characterized by the infiltration of maternal neutrophils in the chorioamniotic membranes. Herein, we investigated whether these infiltrating neutrophils form NETs in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis...
January 3, 2017: American Journal of Reproductive Immunology: AJRI
Eun Young Jung, Byung Yoon Choi, Jihye Rhee, Jaehong Park, Soo-Hyun Cho, Kyo Hoon Park
BACKGROUND: To determine whether the presence of intra-amniotic infection and elevated proinflammatory cytokine levels in amniotic fluid (AF) are associated with failure in the newborn hearing screen (NHS) test in very preterm neonates. METHODS: This is a retrospective cohort study of 112 premature singleton neonates born to women with preterm labor or preterm premature rupture of membranes at ≤32 wk. AF obtained through amniocentesis was cultured, and interleukin-6 (IL-6) and IL-8 levels were determined...
December 7, 2016: Pediatric Research
Nardhy Gomez-Lopez, Roberto Romero, Yi Xu, Derek Miller, Ronald Unkel, Majid Shaman, Suzanne M Jacques, Bogdan Panaitescu, Valeria Garcia-Flores, Sonia S Hassan
OBJECTIVE: Neutrophil extracellular traps (NETs) control microbial infections through their antimicrobial activities attributed to DNA, histones, granules, and cytoplasmic proteins (eg, elastase). Intra-amniotic infection is characterized by the influx of neutrophils into the amniotic cavity; therefore, the aim of this study was to determine whether amniotic fluid neutrophils form NETs in this inflammatory process. METHODS: Amniotic fluid samples from women with intra-amniotic infection (n = 15) were stained for bacteria detection using fluorescent dyes...
November 23, 2016: Reproductive Sciences
Karen L Archabald, Irina A Buhimschi, Mert O Bahtiyar, Antonette T Dulay, Sonya S Abdel-Razeq, Christian M Pettker, Heather S Lipkind, John T Hardy, Megan E McCarthy, Guomao Zhao, Vineet Bhandari, Catalin S Buhimschi
BACKGROUND: To improve neonatal outcomes in pregnancies at heightened risk for early-onset neonatal sepsis (EONS), there is a need to identify fetuses that benefit from expectant management as opposed to early delivery. Detectable haptoglobin and haptoglobin-related protein (Hp&HpRP switch-on status) in cord blood has been proposed as a biomarker of antenatal exposure to intra-amniotic infection and/or inflammation (IAI), an important determinant of EONS. SUBJECTS AND METHODS: We analyzed 185 singleton newborns delivered secondary to preterm premature rupture of membranes (PPROM)...
October 29, 2016: Fetal Diagnosis and Therapy
Alicia Martinez-Varea, Roberto Romero, Yi Xu, Derek Miller, Ahmed I Ahmed, Piya Chaemsaithong, Noppadol Chaiyasit, Lami Yeo, Majid Shaman, Kia Lannaman, Benjamin Cher, Sonia S Hassan, Nardhy Gomez-Lopez
OBJECTIVES: 1) To characterize the cellular composition of the amniotic fluid of patients diagnosed with clinical chorioamnionitis at term, as a function of the presence or absence of microorganisms determined by cultivation techniques, and 2) to characterize the cytokine production by white blood cells present in the amniotic fluid using flow cytometry-based techniques. MATERIALS AND METHODS: Amniotic fluid samples from 20 women who had the diagnosis of clinical chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas)...
October 20, 2016: Journal of Perinatal Medicine
Nicole Marquardt, Martin A Ivarsson, Erik Sundström, Elisabet Åkesson, Elisa Martini, Liv Eidsmo, Jenny Mjösberg, Danielle Friberg, Marius Kublickas, Sverker Ek, Gunilla Tegerstedt, Åke Seiger, Magnus Westgren, Jakob Michaëlsson
Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45(+) cells in AF is represented by a subset of fetal CD103(+) group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF...
September 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Manalee Vishnu Surve, Anjali Anil, Kshama Ganesh Kamath, Smita Bhutda, Lakshmi Kavitha Sthanam, Arpan Pradhan, Rohit Srivastava, Bhakti Basu, Suryendu Dutta, Shamik Sen, Deepak Modi, Anirban Banerjee
Infection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening...
September 2016: PLoS Pathogens
T Myntti, L Rahkonen, A Pätäri-Sampo, M Tikkanen, T Sorsa, J Juhila, O Helve, S Andersson, J Paavonen, V Stefanovic
OBJECTIVE: To evaluate the association of amniotic fluid (AF) matrix metalloproteinase-8 (MMP-8) and cathelicidin concentrations with microbial invasion of the amniotic cavity (MIAC) in pregnancies with preterm prelabor rupture of the membranes or intact membranes. STUDY DESIGN: Amniocentesis was performed in 54 singleton pregnancies between 22(+0) and 34(+2) gestational weeks with suspected intra-amniotic infection. AF-MMP-8 was analysed by immunoassay and AF-cathelicidin by commercial ELISA...
December 2016: Journal of Perinatology: Official Journal of the California Perinatal Association
William E Ackerman, Irina A Buhimschi, Haley R Eidem, David C Rinker, Antonis Rokas, Kara Rood, Guomao Zhao, Taryn L Summerfield, Mark B Landon, Catalin S Buhimschi
INTRODUCTION: We performed RNA sequencing with the primary goal of discovering key placental villous trophoblast (VT) and decidua basalis (DB) transcripts differentially expressed in intra-amniotic infection (IAI)-induced preterm birth (PTB). METHODS: RNA was extracted from 15 paired VT and DB specimens delivered of women with: 1) spontaneous PTB in the setting of amniocentesis-proven IAI and histological chorioamnionitis (n = 5); 2) spontaneous idiopathic PTB (iPTB, n = 5); and 3) physiologic term pregnancy (n = 5)...
August 2016: Placenta
Maria Nikiforou, Esmee M R Jacobs, Matthew W Kemp, Mathias W Hornef, Matthew S Payne, Masatoshi Saito, John P Newnham, Leon E W Janssen, Alan H Jobe, Suhas G Kallapur, Boris W Kramer, Tim G A M Wolfs
Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic C...
2016: Scientific Reports
Ivana Musilova, Tomas Bestvina, Martina Hudeckova, Igor Michalec, Teresa Cobo, Bo Jacobsson, Marian Kacerovsky
BACKGROUND: Preterm prelabor rupture of membranes (PROM) is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm PROM is not broadly used in clinical practice, and therefore a shift towards a non-invasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously...
July 9, 2016: American Journal of Obstetrics and Gynecology
Ivana Musilova, Tomas Bestvina, Martina Hudeckova, Igor Michalec, Teresa Cobo, Bo Jacobsson, Marian Kacerovsky
BACKGROUND: Preterm prelabor rupture of membranes (PROM) is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm PROM is not broadly used in clinical practice, and therefore a shift towards a non-invasive amniotic fluid sampling method is needed. OBJECTIVE: The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously...
July 8, 2016: American Journal of Obstetrics and Gynecology
Fan Zhang, Elizabeth Nance, Zhi Zhang, Venkatasai Jasty, Siva P Kambhampati, Manoj K Mishra, Irina Burd, Roberto Romero, Sujatha Kannan, Rangaramanujam M Kannan
Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality...
September 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Krishna Rao Maddipati, Roberto Romero, Tinnakorn Chaiworapongsa, Piya Chaemsaithong, Sen-Lin Zhou, Zhonghui Xu, Adi L Tarca, Juan Pedro Kusanovic, Ricardo Gomez, Noppadol Chaiyasit, Kenneth V Honn
Bioactive lipids derived from the metabolism of polyunsaturated fatty acids are important mediators of the inflammatory response. Labor per se is considered a sterile inflammatory process. Intra-amniotic inflammation (IAI) due to microorganisms (i.e., intra-amniotic infection) or danger signals (i.e., sterile IAI) has been implicated in the pathogenesis of preterm labor and clinical chorioamnionitis at term. Early and accurate diagnosis of microbial invasion of the amniotic cavity (MIAC) requires analysis of amniotic fluid (AF)...
October 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kara M Rood, Irina A Buhimschi, Katherine Rodewald Millen, Mert O Bahtiyar, Stephen Thung, Taryn Summerfield, Guomao Zhao, William Ackerman, Cynthia Shellhaas, Philip Samuels, Catalin S Buhimschi
PROBLEM: Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in neutrophils and involved in innate immunity by sequestering iron. NGAL's ability to complex with matrix metalloproteinase-9 (MMP-9) and extend its gelatinolytic activity led us to investigate its role in pregnancies complicated by preterm birth (PTB) and intra-amniotic infection/inflammation (IAI). METHOD OF STUDY: We assayed the amniotic fluid (AF) levels of NGAL and MMP-9 in 308 women that had a clinically indicated amniocentesis and a normal pregnancy outcome or PTB...
August 2016: American Journal of Reproductive Immunology: AJRI
Sarah J Stock, Olga Patey, Basky Thilaganathan, Scott White, Lucy L Furfaro, Matthew S Payne, Owen B Spiller, Andres Noé, Rory Watts, Sean Carter, Demelza J Ireland, Alan H Jobe, John P Newnham, Matthew W Kemp
INTRODUCTION: Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (1) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function...
May 23, 2016: Reproductive Sciences
John T Hardy, Irina A Buhimschi, Megan E McCarthy, Guomao Zhao, Christine A Laky, Lydia L Shook, Catalin S Buhimschi
CONTEXT: Microbial invasion of the amniotic fluid (AF) cavity stimulates an inflammatory response that involves activin-A, a pleiotropic mediator member of the TGFβ superfamily involved in connective tissue remodeling. The role of AF follistatin, a natural inhibitor of activin-A, in inflammation-induced preterm birth (PTB), has yet to be determined. OBJECTIVE: The objective of the study was to investigate the relationships between AF activin-A and follistatin in physiological gestation and in pregnancies complicated by PTB and to evaluate a possible role played by the activin-A-follistatin balance in processes leading to PTB and preterm premature rupture of membranes (PPROM)...
July 2016: Journal of Clinical Endocrinology and Metabolism
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