DSpace Angular :: Browsing by Author "Chaiworapongsa, Tinnakorn"

Browsing by Author "Chaiworapongsa, Tinnakorn"

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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).
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.
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.
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.
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
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.
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.
Could alterations in maternal plasma visfatin concentration participate in the phenotype definition of preeclampsia and SGA?
(TAYLOR & FRANCIS LTD, 2010) Mazaki Tovi, Shali; Romero, Roberto; Kim, Sun Kwon; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Mittal, Pooja; Nhan Chang, Chia Ling; Than, Nandor Gabor; Gomez, Ricardo; Nien, Jyh Kae; Edwin, Samuel S.; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.
Objective. Women with preeclampsia and those who delivered a small-for-gestational-age (SGA) neonate share several mechanisms of disease, including chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either preeclampsia or SGA. Compelling evidence suggests that adipose tissue orchestrates both metabolic pathways and immunological responses via the production of adipokines. Visfatin is a novel adipocytokine with metabolic and immunomodulating properties. The objective of this study was to determine whether preeclampsia and SGA are associated with alterations in maternal circulating visfatin concentrations.
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.
Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing
(2024) Garcia-Flores, Valeria; Romero, Roberto; Tarca, Adi L.; Peyvandipour, Azam; Xu, Yi; Galaz, Jose; Miller, Derek; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Berry, Stanley M.; Awonuga, Awoniyi O.; Bryant, David R.; Pique-Regi, Roger; Gomez-Lopez, Nardhy
Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth.
Detection of Anti-HLA Antibodies in Maternal Blood in the Second Trimester to Identify Patients at Risk of Antibody-Mediated Maternal Anti-Fetal Rejection and Spontaneous Preterm Delivery
(2013) Lee, JoonHo; Romero, Roberto; Xu, Yi; Miranda, Jezid; Yoo, Wonsuk; Chaemsaithong, Piya; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor; Yoon, Bo Hyun; Kim, Chong Jai
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.
Low circulating maternal adiponectin in patients with pyelonephritis: adiponectin at the crossroads of pregnancy and infection
(2010) Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kwon Kim, Sun; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Jai Kim, Chong; Gómez Mora, Ricardo Alberto; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan Pedro
Objective: An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design: This cross-sectional study included women in the following groups: 1) normal pregnant women (ns200); and 2) pregnant women with pyelonephritis (ns50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (P-0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P-0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P-0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pregestational body mass index (BMI). Conclusion: 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the antiinflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the intricate interface between inflammation and metabolism during pregnancy
Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate
(TAYLOR & FRANCIS LTD, 2010) Mazaki Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan Chang, Chia Ling; Gomez, Ricardo; Savasan, Zeynep Alpay; Madan, Ichchha; Yoon, Bo Hyun; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.
Objective. Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.
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
Problem
Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia
(TAYLOR & FRANCIS LTD, 2011) Chaiworapongsa, Tinnakorn; Romero, Roberto; Savasan, Zeynep Alpay; Kusanovic, Juan Pedro; Ogge, Giovanna; Soto, Eleazar; Dong, Zhong; Tarca, Adi; Gaurav, Bhatti; Hassan, Sonia S.
Objective: To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and -2 could identify patients at risk for developing preeclampsia (PE) requiring preterm delivery. Study design: Patients presenting with the diagnosis "rule out PE" to the obstetrical triage area of our hospital at <37 weeks of gestation (n = 87) were included in this study. Delivery outcomes were used to classify patients into four groups: I) patients without PE or those with gestational hypertension (GHTN) or chronic hypertension (CHTN) who subsequently developed PE at term (n = 19); II): mild PE who delivered at term (n = 15); III): mild disease (mild PE, GHTN, CHTN) who subsequently developed severe PE requiring preterm delivery (n = 26); and IV): diagnosis of severe PE (n = 27). Plasma concentrations of PlGF, sEng, sVEGFR-1 and -2 were determined at the time of presentation by ELISA. Reference ranges for analytes were constructed by quantile regression in our laboratory (n = 180; 1046 samples). Comparisons among groups were performed using multiples of the median (MoM) and parametric statistics after log transformation. Receiver operating characteristic curves, logistic regression and survival analysis were employed for analysis. Results: The mean MoM plasma concentration of PlGF/sVEGFR-1, PlGF/sEng, PlGF, sVEGFR-1 and -2, and sEng in Group III was significantly different from Group II (all p<0.05). A plasma concentration of PlGF/sVEGFR-1 <= 0.05 MoM or PlGF/sEng <= 0.07 MoM had the highest likelihood ratio of a positive test (8.3, 95% CI 2.8-25 and 8.6, 95% CI 2.9-25, respectively), while that of PlGF <= 0.396 MoM had the lowest likelihood ratio of a negative test (0.08, 95% CI 0.03-0.25). The association between low plasma concentrations of PlGF/sVEGFR-1 (= 0.05 MoM) as well as that of PlGF/sEng (= 0.07 MoM) and the development of severe PE remained significant after adjusting for gestational age at presentation, average systolic and diastolic blood pressure, and a history of chronic hypertension [ adjusted odds ratio (OR) = 27 (95% CI 6.4-109) and adjusted OR 30 (95% CI 6.9-126), respectively]. Among patients who presented < 34 weeks gestation (n = 59), a plasma concentration of PlGF/sVEGFR-1 < 0.033 MoM identified patients who delivered within 2 weeks because of PE with a sensitivity of 93% (25/27) and a specificity of 78% (25/32). This cut-off was associated with a shorter interval-to-delivery due to PE [ hazard ratio = 6 (95% CI 2.5-14.6)]. Conclusions: Plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in the obstetrical triage area. These observations support the value of these biomarkers in the clinical setting for the identification of the patient at risk for disease progression requiring preterm delivery.
Metabolomics in premature labor: A novel approach to identify patients at risk for preterm delivery
(2010) Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Gómez Mora, Ricardo Alberto; Nien Shy, Jyh-Kae; Yoon, Bo Hyun; Mazor, Moshe; Luo, Jingqin; Banks, David; Ryals, John; Beecher, Chris
Objective. Biomarkers for preterm labor (PTL) and delivery can be discovered through the analysis of the transcriptome (transcriptomics) and protein composition (proteomics). Characterization of the global changes in low-molecular weight compounds which constitute the ‘metabolic network’ of cells (metabolome) is now possible by using a ‘metabolomics’ approach. Metabolomic profiling has special advantages over transcriptomics and proteomics since the metabolic network is downstream from gene expression and protein synthesis, and thus more closely reflects cell activity at a functional level. This study was conducted to determine if metabolomic profiling of the amniotic fluid can identify women with spontaneous PTL at risk for preterm delivery, regardless of the presence or absence of intraamniotic infection/inflammation (IAI). Study Design. Two retrospective cross-sectional studies were conducted, including three groups of pregnant women with spontaneous PTL and intact membranes: (1) PTL who delivered at term; (2) PTL without IAI who delivered preterm; and (3) PTL with IAI who delivered preterm. The first was an exploratory study that included 16, 19, and 20 patients in groups 1, 2, and 3, respectively. The second study included 40, 33, and 40 patients in groups 1, 2, and 3, respectively. Amniotic fluid metabolic profiling was performed by combining chemical separation (with gas and liquid chromatography) and mass spectrometry. Compounds were identified using authentic standards. The data were analyzed using discriminant analysis for the first study and Random Forest for the second. Results. (1) In the first study, metabolomic profiling of the amniotic fluid was able to identify patients as belonging to the correct clinical group with an overall 96.3% (53/55) accuracy; 15 of 16 patients with PTL who delivered at term were correctly classified; all patients with PTL without IAI who delivered preterm neonates were correctly identified as such (19/19), while 19/20 patients with PTL and IAI were correctly classified. (2) In the second study, metabolomic profiling was able to identify patients as belonging to the correct clinical group with an accuracy of 88.5% (100/113); 39 of 40 patients with PTL who delivered at term were correctly classified; 29 of 33 patients with PTL without IAI who delivered preterm neonates were correctly classified. Among patients with PTL and IAI, 32/40 were correctly classified. The metabolites responsible for the classification of patients in different clinical groups were identified. A preliminary draft of the human amniotic fluid metabolome was generated and found to contain products of the intermediate metabolism of mammalian cells and xenobiotic compounds (e.g. bacterial products and Salicylamide). Conclusion. Among patients with spontaneous PTL with intact membranes, metabolic profiling of the amniotic fluid can be used to assess the risk of preterm delivery in the presence or absence of infection/inflammation.
Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses
(WALTER DE GRUYTER GMBH, 2010) DiGiulio, Daniel B.; Gervasi, Maria Teresa; Romero, Roberto; Vaisbuch, Edi; Mazaki Tovi, Shali; Kusanovic, Juan Pedro; Seok, Kimberley S.; Gomez, Ricardo; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Oyarzun, Enrique; Kim, Chong Jai; Relman, David A.
Objective: Microbial invasion of the amniotic cavity (MIAC) has been detected in women with preterm labor, preterm prelabor rupture of membranes (PROM), and in patients at term with PROM or in spontaneous labor. Intrauterine infection is recognized as a potential cause of fetal growth restriction; yet, the frequency of MIAC in pregnancies with small-for-gestational-age (SGA) fetuses is unknown. The aim of this study was to determine the frequency, diversity and relative abundance of microbes in amniotic fluid (AF) of women with an SGA neonate using a combination of culture and molecular methods.
Plasma protein Z concentrations in pregnant women with idiopathic intrauterine bleeding and in women with spontaneous preterm labor
(TAYLOR & FRANCIS LTD, 2007) Kusanovic, Juan Pedro; Espinoza, Jimmy; Romero, Roberto; Hoppensteadt, Debra; Nien, Jyh Kae; Kim, Chong Jai; Erez, Offer; Soto, Eleazar; Fareed, Jawed; Edwin, Sam; Chaiworapongsa, Tinnakorn; Than, Nador G.; Yoon, Bo Hyun; Gomez, Ricardo; Papp, Zoltan; Hassan, Sonia S.
Objectives. Preterm parturition has been associated with decidual vascular disorders and excessive thrombin generation. The objective of this study was to examine maternal plasma concentrations of protein Z in normal pregnancies, as well as in those presenting with spontaneous preterm labor (PTL) and intrauterine bleeding during pregnancy.
Polymorphisms in maternal and fetal genes encoding for proteins involved in extracellular matrix metabolism alter the risk for small-for-gestational-age
(TAYLOR & FRANCIS LTD, 2011) Edwards, Digna R. Velez; Romero, Roberto; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn; Pearce, Brad D.; Bartlett, Jacquelaine; Friel, Lara A.; Salisbury, Benjamin A.; Anant, Madan Kumar; Vovis, Gerald F.; Lee, Min Seob; Gomez, Ricardo; Behnke, Ernesto; Oyarzun, Enrique; Tromp, Gerard; Menon, Ramkumar; Williams, Scott M.
Objective. To examine the association between maternal and fetal genetic variants and small-for-gestational-age (SGA).

Browsing by Author "Chaiworapongsa, Tinnakorn"

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