Browsing by Author "Romero, Roberto"

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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 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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    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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    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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    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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    Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia
    (2008) Parimi, Neeta; Tromp, Gerard; Kuivaniemi, Helena; Nien, Jyh K.; Gomez, Ricardo; Romero, Roberto; Goddard, Katrina A.
    Abstract Background In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Methods Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. Results We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. Conclusion The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.Abstract Background In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Methods Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. Results We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. Conclusion The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.
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    Are B cells altered in the decidua of women with preterm or term labor?
    (2019) Leng, Yaozhu; Romero, Roberto; Xu, Yi; Galaz Alarcón, José; Slutsky, Rebecca; Arenas Hernández, Marcia; García Flores, Valeria; Motomura, Kenichiro; Hassan, Sonia S.; Reboldi, Andrea; Gómez López, Nardhy
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    Bacteria and endotoxin in meconium-stained amniotic fluid at term : Could intra-amniotic infection cause meconium passage?
    (2014) Romero, Roberto; Yoon, Bo Hyun; Chaemsaithong, Piya; Cortez, Joséf; Park, ChanWook; González Pérez, Rogelio Iván; Behnke, Ernesto; Hassan, Sonia, S.; Chaiworapongsa, Tinnakorn,; Yeo, Lami
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    Blood pH and gases in fetuses in preterm labor with and without systemic inflammatory response syndrome
    (TAYLOR & FRANCIS LTD, 2012) Romero, Roberto; Soto, Eleazar; Berry, Stanley M.; Hassan, Sonia S.; Pedro Kusanovic, Juan; Yoon, Bo Hyun; Edwin, Samuel; Mazor, Moshe; Chaiworapongsa, Tinnakorn
    Objective: Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: (i) the method/frequency of fetal surveillance and (ii) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: (i) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis and (ii) patients with fetal inflammatory response syndrome (FIRS) vs. those without this condition. Study design: Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to (i) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60) and (ii) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 > 11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, Delta pH and Delta PaO2 were calculated by adjusting for gestational age (. = observed value - mean for gestational age). Non-parametric statistics were employed. Results: No differences in the median Delta pH (-0.026 vs. -0.016), Delta PaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (-2.4 vs. -2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p > 0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p > 0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3 vs. 9.8%; p > 0.05) and fetal hypoxia between fetuses with or without FIRS (12.5 vs. 19.5%; p > 0.05). Conclusions: Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of PTL and delivery.
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    Cellular immune responses in amniotic fluid of women with preterm prelabor rupture of membranes
    (WALTER DE GRUYTER GMBH, 2020) Galaz, Jose; Romero, Roberto; Slutsky, Rebecca; Xu, Yi; Motomura, Kenichiro; Para, Robert; Pacora, Percy; Panaitescu, Bogdan; Hsu, Chaur Dong; Kacerovsky, Marian; Gomez Lopez, Nardhy
    Background: Preterm birth is the leading cause of perinatal morbidity and mortality. Preterm prelabor rupture of membranes (pPROM) occurs in 30% of preterm births; thus, this complication is a major contributor to maternal and neonatal morbidity. However, the cellular immune responses in amniotic fluid of women with pPROM have not been investigated.
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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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    Clarithromycin prevents preterm birth and neonatal mortality by dampening alarmin-induced maternal–fetal infammation in mice
    (2022) Galaz, José; Romero, Roberto; Arenas-Hernandez, Marcia; Farías Jofré, Marcelo Enrique; Motomura, Kenichiro; Liu, Zhenjie; Kawahara, Naoki; Demery-Poulos, Catherine; Liu, Tzu N.; Padron, Justin; Panaitescu, Bogdan; Gomez-Lopez, Nardhy
    Background: One of every four preterm neonates is born to a woman with sterile intra-amniotic inflammation (inflammatory process induced by alarmins); yet, this clinical condition still lacks treatment. Herein, we utilized an established murine model of sterile intra-amniotic inflammation induced by the alarmin high-mobility group box-1 (HMGB1) to evaluate whether treatment with clarithromycin prevents preterm birth and adverse neonatal outcomes by dampening maternal and fetal inflammatory responses. Methods: Pregnant mice were intra-amniotically injected with HMGB1 under ultrasound guidance and treated with clarithromycin or vehicle control, and pregnancy and neonatal outcomes were recorded (n = 15 dams each). Additionally, amniotic fluid, placenta, uterine decidua, cervix, and fetal tissues were collected prior to preterm birth for determination of the inflammatory status (n = 7–8 dams each). Results: Clarithromycin extended the gestational length, reduced the rate of preterm birth, and improved neonatal mortality induced by HMGB1. Clarithromycin prevented preterm birth by interfering with the common cascade of parturition as evidenced by dysregulated expression of contractility-associated proteins and inflammatory mediators in the intra-uterine tissues. Notably, clarithromycin improved neonatal survival by dampening inflammation in the placenta as well as in the fetal lung, intestine, liver, and spleen. Conclusions: Clarithromycin prevents preterm birth and improves neonatal survival in an animal model of sterile intra-amniotic inflammation, demonstrating the potential utility of this macrolide for treating women with this clinical condition, which currently lacks a therapeutic intervention.
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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 IX : in vivo evidence of intra-amniotic inflammasome activation
    (2019) Gomez-López, Nardhy; Romero, Roberto; Maymon, Ely; Kusanovic, Juan Pedro; Panaitescu, Bogdan; Miller, Derek; Pacora, Percy; Tarca, Adi L.; Motomura, Kenichiro; Erez, Offer; Jung, Eunjung J.; Hassan, Sonia S.; Hsu, Chaur Dong
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    Clinical chorioamnionitis at term VIII: a rapid MMP-8 test for the identification of intra-amniotic inflammation
    (2017) Chaiyasit, Noppadol; Romero, Roberto; Chaemsaithong, Piya; Docheva, Nikolina; Bhatti, Gaurav; Kusanovic, Juan Pedro; Dong, Zhong; Yeo, Lami; Pacora, Percy; Hassan,Sonia S.; Erez, Offer
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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.