Browsing by Author "Pedro Kusanovic, Juan"

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    A Signature of Maternal Anti-Fetal Rejection in Spontaneous Preterm Birth: Chronic Chorioamnionitis, Anti-Human Leukocyte Antigen Antibodies, and C4d
    (PUBLIC LIBRARY SCIENCE, 2011) Lee, JoonHo; Romero, Roberto; Xu, Yi; Kim, Jung Sun; Topping, Vanessa; Yoo, Wonsuk; Pedro Kusanovic, Juan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yoon, Bo Hyun; Kim, Chong Jai
    Background: Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth.
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    Characterization of amniotic fluid sludge in preterm and term gestations
    (2022) Pedro Kusanovic, Juan; Jung, Eunjung; Romero, Roberto; Green, Pooja Mittal; Nhan-Chang, Chia-Ling; Vaisbuch, Edi; Erez, Offer; Kim, Chong Jai; Goncalves, Luis F.; Espinoza, Jimmy; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Diaz-Primera, Ramiro; Yeo, Lami; Suksai, Manaphat; Gotsch, Francesca; Hassan, Sonia S.
    Objective To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations. Methods This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count. Results Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (n = 13) had a pus-like appearance; however, after this gestational age, most of the samples [83% (10/12)] appeared to be consistent with vernix; (3) amniotic fluid cultures were positive for microorganisms in 13 patients, of which 10 were preterm gestations before 33 weeks; (4) the most frequent microorganisms retrieved by culture were genital mycoplasmas (Ureaplasma urealyticum [46% (6/13)]), followed by Mycoplasma hominis [31% (4/13)] and Candida albicans [15% (2/13)]; and (5) patients with sonographic particulate matter in preterm gestations frequently presented acute histologic chorioamnionitis and funisitis, but these conditions were rare in patients at term. Conclusion The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.
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    Clinical chorioamnionitis is characterized by changes in the expression of the alarmin HMGB1 and one of its receptors, sRAGE
    (TAYLOR & FRANCIS LTD, 2012) Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Hussein, Youssef; Dong, Zhong; Pedro Kusanovic, Juan; Kim, Chong Jai; Hassan, Sonia S.
    Objective: High mobility group box-1 (HMGB1) protein is an alarmin, a normal cell constituent, which is released into the extracellular environment upon cellular stress/damage and capable of activating inflammation and tissue repair. The receptor for advanced glycation end products (RAGE) can bind HMGB1. RAGE, in turn, can induce the production of pro-inflammatory cytokines; this may be modulated by the soluble truncated forms of RAGE, including soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objectives of this study were to determine whether: 1) clinical chorioamnionitis at term is associated with changes in amniotic fluid concentrations of HMGB1, sRAGE and esRAGE; and 2) the amniotic fluid concentration of HMGB1 changes with labor or as a function of gestational age. Methods: Amniotic fluid samples were collected from the following groups: 1) mid-trimester (n=45); 2) term with (n=48) and without labor (n=22) without intra-amniotic infection; and 3) term with clinical chorioamnionitis (n=46). Amniotic fluid concentrations of HMGB1, sRAGE and esRAGE concentrations were determined by ELISA. Results: 1) the median amniotic fluid HMGB1 concentration was higher in patients at term with clinical chorioamnionitis than in those without this condition (clinical chorioamnionitis: median 3.8 ng/mL vs. term in labor: median 1.8 ng/mL, p=0.007; and vs. term not in labor: median 1.1 ng/mL, p=0.003); 2) in contrast, patients with clinical chorioamnionitis had a lower median sRAGE concentration than those without this condition (clinical chorioamnionitis: median 9.3 ng/mL vs. term in labor: median 18.6 ng/mL, p=0.001; and vs. term not in labor median: 28.4 ng/mL, p<0.001); 3) amniotic fluid concentrations of esRAGE did not significantly change in patients with clinical chorioamnionitis at term (clinical chorioamnionitis: median 5.4 ng/mL vs. term in labor: median 6.1 ng/mL, p=0.9; and vs. term not in labor: median 9.5 ng/mL, p=0.06); and 4) there was no significant difference in the median AF HMGB1 concentration between women at term in labor and those not in labor (p=0.4) and between women in the mid-trimester and those at term not in labor (mid-trimester: median 1.5 ng/mL; p=0.2). Conclusion: An increase in the amniotic fluid HMGB1 concentration and a decrease in sRAGE were observed in clinical chorioamnionitis at term. This finding provides evidence that an alarmin, HMGB1, and one of its receptors, sRAGE, are engaged in the process of clinical chorioamnionitis at term. These changes are quite different from those observed in cases of intra-amniotic infection/inflammation in preterm gestations.
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    Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1
    (TAYLOR & FRANCIS LTD, 2011) Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Xu, Yi; Hussein, Youssef; Dong, Zhong; Pedro Kusanovic, Juan; Kim, Chong Jai; Hassan, Sonia S.
    Objective: Preterm parturition is a syndrome caused by multiple etiologies. Although intra-amniotic infection is causally linked with intrauterine inflammation and the onset of preterm labor, other patients have preterm labor in the absence of demonstrable infection. It is now clear that inflammation may be elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which include pathogen-associated molecular patterns (PAMPs) as well as "alarmins" (endogenous molecules that signal tissue and cellular damage). A prototypic alarmin is high-mobility group box 1 (HMGB1) protein, capable of inducing inflammation and tissue repair when it reaches the extracellular environment. HMGB1 is a late mediator of sepsis, and blockade of HMGB1 activity reduces mortality in an animal model of endotoxemia, even if administered late during the course of the disorder. The objectives of this study were to: (1) determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in amniotic fluid concentrations of HMGB1; and (2) localize immunoreactivity of HMGB1 in the fetal membranes and umbilical cord of patients with chorioamnionitis. Methods: Amniotic fluid samples were collected from the following groups: (1) preterm labor with intact membranes (PTL) with (n = 42) and without IAI (n = 84); and (2) preterm prelabor rupture of membranes (PROM) with (n = 38) and without IAI (n = 35). IAI was defined as either a positive amniotic fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) >= 2.6 ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA. Immunofluorescence staining for HMGB1 was performed in the fetal membranes and umbilical cord of pregnancies with acute chorioamnionitis. Results: (1) Amniotic fluid HMGB1 concentrations were higher in patients with IAI than in those without IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs. without IAI; median 0.98 ng/mL; p < 0.001; and preterm PROM with IAI median 7.3 ng/mL vs. without IAI median 2.6 ng/mL; p = 0.002); (2) patients with preterm PROM without IAI had a higher median amniotic fluid HMGB1 concentration than those with PTL and intact membranes without IAI (p < 0.001); and (3) HMGB1 was immunolocalized to amnion epithelial cells and stromal cells in the Wharton's jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of the chorioamniotic connective tissue layer and infiltrating neutrophils showed diffuse cytoplasmic HMGB1 immunoreactivity. Conclusions: (1) intra-amniotic infection/inflammation is associated with elevated amniotic fluid HMGB1 concentrations regardless of membrane status; (2) preterm PROM was associated with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes, suggesting that rupture of membranes is associated with an elevation of alarmins; (3) immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton's jelly and cells involved in the innate immune response; and (4) we propose that HMGB1 released from stress or injured cells into amniotic fluid may be responsible, in part, for intra-amniotic inflammation due to non-microbial insults.
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    Effect of a model based on education and teleassistance for the management of obstetric emergencies in 10 rural populations from Colombia
    (2022) Fernanda Escobar, Maria; Paula Echavarria, Maria; Carlos Gallego, Juan; Riascos, Natalia; Vasquez, Hilda; Nasner, Daniela; Pabon, Stephanie; Alexandra Castro, Zindy; Augusto Cardona, Didier; Milena Castro, Ana; Ramos, Isabella; Antonia Hincapie, Maria; Pedro Kusanovic, Juan; Marcela Martinez-Ruiz, Diana; Andres Carvajal, Javier
    Introduction Pregnant women and health providers in rural areas of low-income and middle-income countries face multiple problems concerning high-quality obstetric care. This study was performed to identify changes in maternal and perinatal indicators after implementing a model based on education and telecare between a high-complexity hospital in 10 low-complexity hospitals in a southwestern region of Colombia. Methods A quasiexperimental study with a historic control group and without a pretest was conducted between 2017 and 2019 to make comparisons before and after obstetric emergency care through the use of teleassistance from 10 primary care centers to the referral center (Fundacion Valle del Lili, FVL). Results A total of 470 patients were treated before teleassistance implementation and 154 patients were treated after teleassistance implementation. After program implementation, the maternal clinical indicators showed a 65% reduction in the number of obstetric patients who were referred with obstetric emergencies. The severity of maternal disease that was measured at the time of admission to level IV through the Modified Early Obstetric Warning System score was observed to decrease. Conclusion The implementation of a model based on education and teleassistance between low-complexity hospitals and tertiary care centers generated changes in indicators that reflect greater access to rural areas, lower morbidity at the time of admission, and a decrease in the total number of emergency events.
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    Gingival Crevicular Placental Alkaline Phosphatase Is an Early Pregnancy Biomarker for Pre-Eclampsia
    (2021) Chaparro, Alejandra; Monckeberg, Maximiliano; Realini, Ornella; Hernandez, Marcela; Param, Fernanda; Albers, Daniela; Ramirez, Valeria; Pedro Kusanovic, Juan; Romero, Roberto; Rice, Gregory; Illanes, Sebastian E.
    Early and innovative diagnostic strategies are required to predict the risk of developing pre-eclampsia (PE). The purpose of this study was to evaluate the performance of gingival crevicular fluid (GCF) placental alkaline phosphatase (PLAP) concentrations to correctly classify women at risk of PE. A prospectively collected, retrospectively stratified cohort study was conducted, with 412 pregnant women recruited at 11-14 weeks of gestation. Physical, obstetrical, and periodontal data were recorded. GCF and blood samples were collected for PLAP determination by ELISA assay. A multiple logistic regression classification model was developed, and the classification efficiency of the model was established. Within the study cohort, 4.3% of pregnancies developed PE. GCF-PLAP concentration was 3- to 6-fold higher than in plasma samples. GCF-PLAP concentrations and systolic blood pressure were greater in women who developed PE (p = 0.015 and p < 0.001, respectively). The performance of the multiparametric model that combines GCF-PLAP concentration and the levels of systolic blood pressure (at 11-14 weeks gestation) showed an association of systolic blood pressure and GCF-PLAP concentrations with the likelihood of developing PE (OR:1.07; 95% CI 1.01-1.11; p = 0.004 and OR:1.008, 95% CI 1.000-1.015; p = 0.034, respectively). The model had a sensitivity of 83%, a specificity of 72%, and positive and negative predictive values of 12% and 99%, respectively. The area under the receiver operating characteristic (AUC-ROC) curve was 0.77 and correctly classified 72% of PE pregnancies. In conclusion, the multivariate classification model developed may be of utility as an aid in identifying pre-symptomatic women who subsequently develop PE.
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    Hematologic profile of the fetus with systemic inflammatory response syndrome
    (WALTER DE GRUYTER GMBH, 2012) Romero, Roberto; Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Berry, Stanley M.; Pedro Kusanovic, Juan; Hassan, Sonia S.; Yoon, Bo Hyun; Edwin, Samuel; Mazor, Moshe
    Objective: The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic profile of fetuses with FIRS.
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    Impact of the change of the Atalah standard cut-off point to classify underweight nutritional status during pregnancy
    (2021) Araya, Marcela B.; Pedro Kusanovic, Juan; Corvalan, Camila; Luisa Garmendia, Maria
    Chile, and several Latin American countries, use the Atalah standard to assess nutritional status during pregnancy. However, this standard (underweight: pre-pregnancy body mass index (BMI)<20 kg/m(2) and normal weight: pre-pregnancy BMI= 20-24.9 kg/m(2)) differ from those recommended by the US Institute of Medicine (IOM2009) (underweight: BMI<18.5 kg/m(2) and normal weight: 18.5-24.9 kg/m(2)). Using a large population database from a Chilean public hospital, we compared the prevalence of underweight and normal weight at the beginning of pregnancy with Atalah and IOM2009 standards. Additionally, we evaluated the performance of both standards in detecting adverse neonatal outcomes and gestational weight gain. Methods: Data from clinical records of single birth pregnancies (n= 59,476) at the Sotero del Rio Hospital, between 2003-2012 were collected. We compared 1. nutritional status, 2. proportion of excessive gestational weight gain, 3. association between nutritional status and neonatal outcomes (large/small for gestational age, low birth weight, preterm birth and macrosomia), using logistic regression models, and 4. Sensitivity, specificity, and predictive values to predict adverse neonatal outcomes per nutritional status. Results: Pre-pregnancy underweight decreased from 8.6% to 2.5% and women with BMI between 18.5-19.9kg/m(2), who exceeded the recommended gestational weight gain increased from 32.7% to 49.2% when using IOM2009 instead of Atalah. Both standards showed low sensitivity, but the IOM2009 cut-off points showed better specificity for identifying healthy newborns. Conclusion: The cut-off points recommended by the IOM2009 better identify the prevalence of underweight and normal weight during pregnancy without increasing neonatal risk. This study supports the recent change of the Ministry of Health in adopting the WHO cut-off points during pregnancy.
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    Maternal HLA Panel-Reactive Antibodies in Early Gestation Positively Correlate with Chronic Chorioamnionitis: Evidence in Support of the Chronic Nature of Maternal Anti-fetal Rejection
    (WILEY, 2011) Lee, JoonHo; Romero, Roberto; Xu, Yi; Kim, Jung Sun; Park, Ji Young; Pedro Kusanovic, Juan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai
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    The pattern and magnitude of "in vivo thrombin generation" differ in women with preeclampsia and in those with SGA fetuses without preeclampsia
    (2018) Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Pedro Kusanovic, Juan; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Mittal, Pooja; Edwin, Samuel S.; Nhan-Chang, Chia-Ling; Than, Nandor Gabor; Kim, Chong Jai; Kim, Sun Kwon; Yeo, Lami; Mazor, Moshe; Hassan, Sonia S.
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    Tissue factor activity in women with preeclampsia or SGA: a potential explanation for the excessive thrombin generation in these syndromes
    (2018) Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Than, Nandor Gabor; Pedro Kusanovic, Juan; Mazaki-Tovi, Shali; Gotsch, Francesca; Mittal, Pooja; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Chong Jai; Nhan-Chang, Chia-Ling; Kim, Sun Kwon; Yeo, L