Browsing by Author "Kusanovic, Juan Pedro"

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    A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)
    (MOSBY-ELSEVIER, 2010) Romero, Roberto; Friel, Lara A.; Edwards, Digna R. Velez; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn; Pearce, Brad D.; Bartlett, Jacquelaine; Salisbury, Benjamin A.; Anant, Madan Kumar; Vovis, Gerald F.; Lee, Min Seob; Gomez, Ricardo; Behnke, Ernesto; Oyarzun, Enrique; Tromp, Gerard; Williams, Scott M.; Menon, Ramkumar
    OBJECTIVE: We sought to determine whether maternal/fetal single-nucleotide polymorphisms (SNPs) in candidate genes are associated with preterm prelabor rupture of membranes (pPROM).
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    A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate
    (TAYLOR & FRANCIS LTD, 2008) Romero, Roberto; Nien, Jyh Kae; Espinoza, Jimmy; Todem, David; Fu, Wenjiang; Chung, Hwan; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Mazaki Tovi, Shali; Gomez, Ricardo; Edwin, Sam; Chaiworapongsa, Tinnakorn; Levine, Richard J.; Karumanchi, S. Ananth
    Introduction. Accumulating evidence suggests that an imbalance between pro-angiogenic (i.e., vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)) and anti-angiogenic factors (i.e., soluble VEGF receptor-1 (sVEGFR-1, also referred to as sFlt1)) is involved in the pathophysiology of preeclampsia (PE). Endoglin is a protein that regulates the pro-angiogenic effects of transforming growth factor , and its soluble form has recently been implicated in the pathophysiology of PE. The objective of this study was to determine if changes in maternal plasma concentration of these angiogenic and anti-angiogenic factors differ prior to development of disease among patients with normal pregnancies and those destined to develop PE (preterm and term) or to deliver a small for gestational age (SGA) neonate.
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    A Novel ERAP2 Haplotype Structure in a Chilean Population: Implications for ERAP2 Protein Expression and Preeclampsia Risk
    (2013) Vanhille, Derek L.; Hill, Lori D.; Hilliard, DaShaunda D.; Lee, Eun D.; Teves, Maria E.; Srinivas, Sindhu; Kusanovic, Juan Pedro; Gómez Mora, Ricardo Alberto; Stratikos, Efstratios
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    A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery
    (2006) Nien, J. K.; Yoon, B. H.; Espinoza, J.; Kusanovic, Juan Pedro; Erez, O.; Soto, E.; Richani, K.; Gómez Mora, Ricardo Alberto; Hassan, S.; Mazor, M.; Edwin, S.; Bahado-Singh, R.; Romero, R.
    Objective: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. Study design: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. Results: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). Conclusion: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intraamniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery.
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    A role for CXCL13 in the host response to intra-amniotic infection
    (2007) Nhan-Chang, Chia-Ling; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel S.; Erez, Offer; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara; Vaisbuch, Edi; Than, Nandor Gabor; Mazaki-Tovi, Shali; Hassan, Sonia
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    A role for microRNAs - Key regulators of gene expression - In chorioamnionitis and parturition
    (2006) Montenegro, Daniel; Romero, Roberto; Pineles, Beth L.; Tarca, Adi L.; Kim, Yeon Mee; Draghici, Sorin; Kusanovic, Juan Pedro; Erez, Offer; Mazakitovi, Shali; Hassan, Sonia; Espinoza, Jimmy; Kim, Chong Jai
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    Adiponectin in severe preeclampsia
    (2007) Nien, J. K.; Mazaki-Tovi, S.; Romero, R.; Erez, O.; Kusanovic, Juan Pedro; Gotsch, F.; Pineles, B. L.; Gómez Mora, Ricardo Alberto; Edwin, S.; Mazor, M.; Espinoza, J.; Yoon, B. H.; Hassan, S. S.
    Aims: Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods: This case-control study included two groups: (1) patients with severe preeclampsia (ns50) and (2) patients with normal pregnancies (ns150). Pulsedwave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results: (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions: Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolicallyaltered, anti-angiogenic and pro-atherogenic state of severe preeclampsia.
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    Adiponectin multimers in maternal plasma
    (2008) Mazaki-Tovi, S.; Romero, R.; Kusanovic, Juan Pedro; Erez, O.; Vaisbuch, E.; Gotsch, F.; Mittal, P.; Than, G. N.; Nhan-Chang, C.; Chaiworapongsa, T.; Edwin, S.; Camacho, N.; Nien Shy, Jyh-Kae; Hassan, S. S.
    Objective: Adiponectin is an anti-diabetic, anti-atherogenic, anti-inflammatory, and angiogenic adipokine that circulates in oligomeric complexes including: low molecular weight (LMW) trimers, medium molecular weight (MMW) hexamers, and high molecular weight (HMW) isoforms. The aim of this study was to determine whether there are changes in adiponectin multimers in pregnancy and as a function of maternal weight. Study design: In this cross-sectional study, plasma concentrations of total, HMW, MMW, and LMW adiponectin were determined in women included in three groups: (1) normal pregnant women of normal body mass index (BMI) (n ¼ 466), (2) overweight pregnant women (BMI 25; n ¼ 257), and (3) non-pregnant women of normal weight (n ¼ 40). Blood samples were collected once from each woman between 11 and 42 weeks of gestation. Plasma adiponectin multimer concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. Results: (1) The median HMW adiponectin concentration and the median HMW/total adiponectin ratio were significantly higher, and the median LMW adiponectin concentration was significantly lower in pregnant women than in non-pregnant women. (2) Among pregnant women, the median plasma concentration of total, HMW, and MMW adiponectin was significantly higher in normal weight women than in overweight patients. (3) Maternal HMW was the most prevalent adiponectin multimer regardless of gestational age or BMI status. (4) There were no significant differences in the median concentration of total, MMW, and LMW adiponectin and their relative distribution with advancing gestation. Conclusion: Human pregnancy is characterized by quantitative and qualitative changes in adiponectin multimers, especially the most active isoform, HMW adiponectin.
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    Allergy-induced preterm labor after the ingestion of shellfish
    (TAYLOR & FRANCIS LTD, 2010) Romero, Roberto; Kusanovic, Juan Pedro; Munoz, Hernan; Gomez, Ricardo; Lamont, Ronald F.; Yeo, Lami
    Preterm parturition is a syndrome caused by several mechanisms of disease, including intrauterine infection/inflammation, uteroplacental ischemia, uterine overdistension, cervical disease, maternal/fetal stress, abnormal allogeneic responses, allergic reactions, and unknown insults. An allergic-like mechanism was proposed as a potential etiology for the preterm parturition syndrome, based on the observation that eosinophils were present in the amniotic fluid in a fraction of women with preterm labor and a history of allergy, coupled with the observation that conditioned media from degranulated mast cells (the effector cells of type 1 hypersensitivity) induced contractility of human myometrial strips. This communication describes a case of a pregnant woman who had an allergic reaction and regular uterine contractions after the ingestion of lobster meat, to which she was known to be allergic. Preterm labor subsided after the treatment of antihistamines and steroids. The patient subsequently delivered at term. At follow-up, the child was diagnosed with atopy and asthma, and required frequent use of inhaled corticosteroids and beta-2 adrenergic agents. The immunological basis for preterm labor induced by an allergic-like reaction (hypersensitivity) is reviewed.
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    Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition
    (2008) Chaiworapongsa, T.; Erez, O.; Kusanovic, Juan Pedro; Vaisbuch, E.; Mazaki-Tovi, S.; Gotsch, F.; Than, N. G.; Mittal, P.; Kim, Y. M.; Camacho, N.; Edwin, S.; Gómez Mora, Ricardo Alberto; Hassan, S. S.; Romero, R.
    Objective: Heat shock protein (HSP) 70, a conserved member of the stress protein family, is produced in almost all cell types in response to a wide range of stressful stimuli, and its production has a survival value. Evidence suggests that extracellular HSP70 is involved in the activation of the innate and adaptive immune response. Furthermore, increased mRNA expression of HSP70 has been observed in human fetal membranes following endotoxin stimulation. This study was conducted to determine the changes in amniotic fluid HSP70 concentrations during pregnancy, term and preterm parturition, intra-amniotic infection (IAI), and histologic chorioamnionitis. Study design. A cross-sectional study was conducted in 376 pregnant women in the following groups: (1) women with a normal pregnancy who were classified into the following categories: (a) women in the mid-trimester (14–18 weeks) who underwent amniocentesis for genetic indications and delivered normal infants at term (n¼72); (b) women at term not in labor (n ¼ 23); and (c) those at term in labor (n ¼ 48). (2) Women with spontaneous preterm labor and intact membranes who were subdivided into the following categories: (a) preterm labor who delivered at term without IAI (n ¼ 42); (b) preterm labor who delivered preterm without IAI (n ¼ 57); and (c) preterm labor and delivery with IAI (n ¼ 30). (3) Women with preterm prelabor rupture of membranes (PROM) with (n ¼ 50) and without (n ¼ 54) IAI. Among patients with preterm labor with intact membranes and preterm PROM who delivered within 72 hours of amniocentesis, placenta, umbilical cord, and chorioamniotic membranes were collected and assessed for the presence or absence of acute inflammatory lesions in the extraplacental membranes (histologic chorioamnionitis) and/or umbilical cords (funisitis). HSP70 concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of 50.05 was considered statistically significant. Results. Immunoreactive HSP70 was detected in 88% (332/376) of amniotic fluid samples. The median amniotic fluid HSP70 concentration was significantly higher in women at term without labor than in those in the mid-trimester (term no labor: median 34.9 ng/mL, range 0–78.1 ng/mL vs. mid-trimester; median 6.6 ng/mL, range 0–20.8 ng/mL; p50.001). Among patients with spontaneous preterm labor and preterm PROM, those with IAI had a significantly higher median amniotic fluid HSP70 concentration than those without IAI (preterm labor with IAI: median 82.9 ng/mL, range 0–500 ng/mL vs. preterm labor without IAI: median 41.7 ng/mL, range 0–244 ng/mL; p ¼ 0.001; preterm PROM with IAI: median 86.5 ng/mL, range 0– 428 ng/mL vs. preterm PROM without IAI: median 55.9 ng/mL, range 14.9–299.9 ng/mL; p ¼ 0.007). There was no significant difference in the median amniotic fluid HSP70 concentration between patients with preterm labor who delivered preterm without IAI and those who delivered at term (p ¼ 0.6). However, among patients with preterm labor without IAI, there was an inverse relationship between amniotic fluid concentration of HSP70 and the amniocentesis-to-spontaneous delivery interval (Spearman’s Rho ¼70.26; p ¼ 0.02). Patients with histologic chorioamnionitis/funisitis had a significantly higher median amniotic fluid HSP70 concentration than those without inflammation (inflammation: median 108.7 ng/mL, range 0– 500 ng/mL vs. without inflammation: median 67.9 ng/mL, range 7.1–299.9 ng/mL; p ¼ 0.02). Women at term in labor had a median amniotic fluid concentration of HSP70 significantly higher than those not in labor (term in labor: median 60.7 ng/mL, range 0–359.9 ng/mL vs. term not in labor: median 34.9 ng/mL, range 0–78.1 ng/mL; p ¼ 0.02).
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    An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome
    (TAYLOR & FRANCIS LTD, 2011) Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.
    Methods. aEuro integral Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n aEuroS== aEuroS16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of > 11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis.
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    Characterization of the Fetal Blood Transcriptome and Proteome in Maternal Anti-Fetal Rejection: Evidence of a Distinct and Novel Type of Human Fetal Systemic Inflammatory Response
    (2013) Lee, JoonHo; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L.; Xu, Yu; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S.; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai
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    Characterization of visceral and subcutaneous adipose tissue transcriptome and biological pathways in pregnant and non-pregnant women : evidence for pregnancy-related regional-specific differences in adipose tissue
    (2015) Mazaki-Tovi, Shali; Vaisbuch, Edi; Tarca, Adi L.; Kusanovic, Juan Pedro; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Romero, Roberto
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    Clinical chorioamnionitis at term : the amniotic fluid fatty acyl lipidome
    (2016) Chaiworapongsa, T.; Chaemsaithong, P.; Zhou, S.; Xu, Z.; Tarca, A.; Kusanovic, Juan Pedro; Gomez, Ricardo; Docheva, N.; Honn, K.; Maddipati, K.; Romero, R.
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    Clinical chorioamnionitis at term I : microbiology of the amniotic cavity using cultivation and molecular techniques
    (2015) Romero, R.; Miranda, J.; Kusanovic, Juan Pedro; Chaiworapongsa, T.; Chaemsaithong, P.; Martinez, A.; Gotsch, F.; Dong, Z.; Ahmed, A.
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    Clinical chorioamnionitis at term II : the intra-amniotic inflammatory response
    (2016) Romero, Roberto; Chaemsaithong, Piya; Steven J. Korzeniewski; Tarca, Adi L.; Bhatti, Gaurav; Xu, Zhonghui; Kusanovic, Juan Pedro
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    Clinical chorioamnionitis at term II: The intra-amniotic inflammatory response
    (2016) Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Tarca, Adi L.; Bhatti, Gaurav; Xu, Zhonghui; Kusanovic, Juan Pedro; Dong, Zhong; Docheva, Nikolina; Martínez Varea, Alicia; Yoon, Bo Hyun; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Yeo, Lami
    Objective: Recent studies indicate that clinical chorioamnionitis is a heterogeneous condition and only approximately one-half of the patients have bacteria in the amniotic cavity, which is often associated with intra-amniotic inflammation. The objective of this study is to characterize the nature of the inflammatory response within the amniotic cavity in patients with clinical chorioamnionitis at term according to the presence or absence of 1) bacteria in the amniotic cavity and 2) intra-amniotic inflammation. Materials and methods: A retrospective cross-sectional case-control study was conducted to examine cytokine and chemokine concentrations in the amniotic fluid (AF). Cases consisted of women with clinical chorioamnionitis at term (n=45). Controls were women with uncomplicated pregnancies at term who did not have intra-amniotic inflammation and were in labor (n=24). Women with clinical chorioamnionitis were classified according to the results of AF cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and AF concentration of interleukin-6 (IL-6) into those: 1) without intra-amniotic inflammation, 2) with microbial-associated intra-amniotic inflammation, and 3) with intra-amniotic inflammation without detectable bacteria. The AF concentrations of 29 cytokines/chemokines were determined using sensitive and specific V-PLEX immunoassays. Results: 1) The AF concentrations of pro- and anti-inflammatory cytokines/chemokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), macrophage inflammatory protein-1 beta (MIP-1β), and interleukin-8 (IL-8) (except Eotaxin-3) were significantly higher in women with clinical chorioamnionitis at term than in controls (term labor without intra-amniotic inflammation); 2) patients with microbial-associated intra-amniotic inflammation, and those with intra-amniotic inflammation without detectable bacteria, had a dramatic differential expression of cytokines and chemokines in AF compared to patients with spontaneous labor without intra-amniotic inflammation. However, no difference could be detected in the pattern of the intra-amniotic inflammatory response between patients with intra-amniotic inflammation with and without detectable bacteria; and 3) in patients with clinical chorioamnionitis at term but without intra-amniotic inflammation, the behavior of cytokines and chemokines in the AF was similar to those in spontaneous labor at term. Conclusions: Patients with clinical chorioamnionitis who had microbial-associated intra-amniotic inflammation or intra-amniotic inflammation without detectable bacteria had a dramatic upregulation of the intra-amniotic inflammatory response assessed by amniotic fluid concentrations of cytokines. A subset of patients with term clinical chorioamnionitis does not have intra-amniotic infection/inflammation, as demonstrated by elevated AF concentrations of inflammation-related proteins, when compared to women in term labor with uncomplicated pregnancies, suggesting over-diagnosis. These observations constitute the first characterization of the cytokine/chemokine network in the amniotic cavity of patients with clinical chorioamnionitis at term.
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    Clinical chorioamnionitis at term III : how well do clinical criteria perform in the identification of proven intra-amniotic infection?
    (2016) Martinez Varea, A.; Ahmed, A.; Yoon, B.; Hassan, S.; Chaiworapongsa, T.; Yeo, L.; Romero, R.; Chaemsaithong, P.; Korzeniewski, S.; Kusanovic, Juan Pedro; Docheva, N.
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    Clinical chorioamnionitis at term IV : the maternal plasma cytokine profile
    (2016) Romero, R.; Chaemsaithong, P.; Docheva, N.; Korzeniewski, S.; Tarca, A.; Bhatt,i G.; Xu, Z.; Kusanovic, Juan Pedro; Dong, Z.; Chaiyasit, N.; Ahmed, A.; Yoon, B.; Hassan, S.; Chaiworapongsa, T.; Yeo, L.