Browsing by Author "Gotsch, Francesca"

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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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    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.
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    Does a perturbation in visfatin homeostasis participate in the phenotype definition of preeclampsia and SGA?
    (2009) Kim, Sun Kwon; Romero, Roberto; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor; Gotsch, Francesca; Nhan-Chang, Chia-Ling; Chiaworapongsa, Tinnakorn; Gómez Mora, Ricardo Alberto; Mittal, Pooja; Hassan, Sonia; Pacora, Percy; Yeo, Lami
    Objective: Women with preeclampsia (PE) 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 PE or SGA (Ness&Sibai AJOG 2006;195:40). 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 PE and SGA are associated with alterations in maternal circulating visfatin concentrations. Methods: This cross-sectional study included 255 pregnant women in the following groups: 1) normal pregnancy (n = 158); 2) patients with PE (n = 43) of which 32 had an AGA and 11 had an SGA neonate; and 3) patients who delivered an SGA neonate without PE (n = 54). Maternal plasma visfatin concentrations were measured by ELISA. Non-parametric tests and multiple linear regression analysis were used. Results: 1) Women who delivered an SGA neonate had higher median maternal plasma visfatin concentration than those with normal pregnancy (median: 20.0ng/ml, interquartile range: 17.2–24.6 vs. 15.2 ng/ml, 12.1–19.2, respectively; p. Conclusion: 1) Mothers with SGA, but not with PE, had a higher maternal plasma visfatin concentration than those with a normal pregnancy; 2) This finding suggests differential involvement of adipokines in SGA and PE; 3) We propose that perturbation of adipokine homeostasis may be implicated in the phenotypic definition and distinction of PE and SGA
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    Early Rapid Growth, Early Birth: Accelerated Fetal Growth and Spontaneous Late Preterm Birth
    (2009) Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis; Hassa, Sonia; Gómez Mora, Ricardo Alberto; Nien Shy, Jyh-Kae; Edward A. Frongillo; Romero, Roberto
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    Evidence for a polarized Th1 response in the maternal circulation in women with preterm labor and intra-amniotic inflammation/infection
    (2006) Espinoza, Jimmy; Kusanovic, Juan Pedro; Hassan, Sonia; Edwin, Samuel S.; Gotsch, Francesca; Kim, Chong Jai; Than, Nandor Gabor; Erez, Offer; Nien, Jyh Kae; Gómez Mora, Ricardo Alberto; Yoon, Bo Hyun; Romer, Roberto
    OBJECTIVE: Most work examining the immune response to intra-amniotic infection has focused on the study of amniotic fluid (AF) cytokines. An adequate characterization of the full range of maternal pro- and antiinflammatory cytokines is lacking. This is important, because of emerging evidence that complications of infection result from an anti-inflammatory response. The purpose of this study was to characterize the maternal cytokine response in women with preterm labor with and without intra-amniotic infection/inflammation (IAI). STUDY DESIGN: This study focused on patients with preterm labor in the following groups: 1) term delivery (n = 157); 2) preterm delivery without IAI (n = 126); and 3) IAI (n = 50). IAI was defined as a positive AF culture or an elevated AF WBC count. Maternal plasma concentrations of interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha were determined. A p!0.05 was considered significant. RESULTS: 1) Patients with IAI had higher plasma concentrations of IL-6 than those without IAI who delivered preterm [median: 12.5 pg/ml, range: 0-355.5 vs.7.4 pg/ml, range: 0.74-179.3; p = 0.04), and those who delivered at term (median: 5 pg/ml, range: 0-541.4; p = 0.01); 2) Patients with IAI had higher plasma concentrations of IL-8 than those who delivered at term (median:11.1 pg/ml, range: 0.29-82 vs. median: 6 pg/ml, range: 0.4-84.3; p = 0.02) but not than those without IAI who delivered preterm (median: 7.9, range: 1.3-90.2; pO0.05); and 3) There were no significant differences in the plasma concentrations of the rest of the cytokines (11 of 13) among groups. CONCLUSION: IL6 and IL8 are increased in the maternal circulation in cases of intra-amniotic infection/inflammation. The lack of a demonstrable anti-inflammatory response is in sharp contrast to what has been reported in non-pregnant patients
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    Growth Perturbations in a Phenotype with Rapid Fetal Growth Preceding Preterm Labor and Term Birth
    (WILEY, 2009) Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Kae Nien, Jyh; Frongillo, Edward A.; Romero, Roberto
    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode. Am. J. Hum. Biol. 21:782-792, 2009. (C) 2009 Wiley-Liss, Inc.
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    Isobaric labeling and tandem mass spectrometry: A novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation
    (TAYLOR & FRANCIS LTD, 2010) Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Vaisbuch, Edi; Mazaki Tovi, Shali; Moser, Allan; Tam, Sunny; Leszyk, John; Master, Stephen R.; Juhasz, Peter; Pacora, Percy; Ogge, Giovanna; Gomez, Ricardo; Yoon, Bo H.; Yeo, Lami; Hassan, Sonia S.; Rogers, Wade T.
    Methods. A cross-sectional study was designed and included AF samples from patients with spontaneous PTL and intact membranes in the following groups: (1) patients without IAI who delivered at term (n = 26); (2) patients who delivered preterm without IAI (n = 25); and (3) patients with IAI (n = 24). Proteomic profiling of AF samples was performed using a workflow involving tryptic digestion, iTRAQ labeling and multiplexing, strong cation exchange fractionation, and liquid chromatography tandem mass spectrometry. Twenty-five separate 4-plex samples were prepared and analyzed.
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    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
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    Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods
    (WALTER DE GRUYTER GMBH, 2010) DiGiulio, Daniel B.; Gervasi, MariaTeresa; Romero, Roberto; Mazaki Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Seok, Kimberley S.; Gomez, Ricardo; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Oyarzun, Enrique; Kim, Chong Jai; Relman, David A.
    Objective: Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined. The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia.
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    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.
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    Sex Differences in Fetal Growth Responses to Maternal Height and Weight
    (WILEY, 2010) Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Gomez, Ricardo; Kae Nien, Jyh; Frongillo, Edward A.; Romero, Roberto
    Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3,495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n = 1,814 males, n = 1,681 females) with birth gestational age, maternal parity, and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth before 18 gestational weeks of age (P = 0.006), and prepregnancy maternal weight and body mass index subsequently had influence (P < 0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (P = 0.003) and more responsive to maternal height among lighter mothers (P <= 0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 g occurred among neonates of the shortest and lightest mothers (P = 0.08), compared to 150 and 191 g among short and heavy mothers, and tall and light-weight mothers, respectively (P = 0.01). Sex differences in response to maternal size are under-appreciated sources of variation in fetal growth studies and may reflect differential growth strategies. Am. J. Hum. Biol. 22:431-443, 2010. (C) 2009 Wiley-Liss, Inc.
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    Should Bilateral Uterine Artery Notching Be Used in the Risk Assessment for Preeclampsia, Small-for-Gestational-Age, and Gestational Hypertension?
    (WILEY, 2010) Espinoza, Jimmy; Kusanovic, Juan Pedro; Bahado Singh, Ray; Gervasi, Maria Teresa; Romero, Roberto; Lee, Wesley; Vaisbuch, Edi; Mazaki Tovi, Shali; Mittal, Pooja; Gotsch, Francesca; Erez, Offer; Gomez, Ricardo; Yeo, Lami; Hassan, Sonia S.
    Objective. The purpose of this study was to determine the value of bilateral uterine artery notching in the second trimester in the risk assessment for preeclampsia, gestational hypertension, and small-for-gestational-age (SGA) without preeclampsia. Methods. This prospective cohort study included 4190 singleton pregnancies that underwent ultrasound examination between 23 and 25 weeks' gestation. The 95th percentiles of the mean pulsatility index (PI) and resistive index (RI) of both uterine arteries were calculated. Multivariable logistic regression analyses were performed to determine if bilateral uterine artery notching is an independent explanatory variable for the occurrence of preeclampsia, early-onset preeclampsia (<= 34 weeks), late-onset preeclampsia (>34 weeks), gestational hypertension, and delivery of an SGA neonate without preeclampsia, while controlling for confounding factors. Results. (1) The prevalence of preeclampsia, early-onset preeclampsia, late-onset preeclampsia, SGA, and gestational hypertension were 3.4%, 0.5%, 2.9%, 10%, and 7.9%, respectively; (2) 7.2% of the study population had bilateral uterine artery notching; and (3) bilateral uterine artery notching was an independent explanatory variable for the development of preeclampsia (odds ratio [OR] 2.1; 95% confidence interval [CI], 1.28-3.36), early-onset preeclampsia (OR, 4.47; 95% CI, 1.50-13.35), and gestational hypertension (OR, 1.50; 95% CI, 1.02-2.26), but not for late-onset preeclampsia or SGA. Conclusions. Bilateral uterine notching between 23 and 25 weeks' gestation is an independent risk factor for the development of early-onset preeclampsia and gestational hypertension. Thus, bilateral uterine artery notching should be considered in the assessment of risk for the development of these pregnancy complications.
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    The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age
    (TAYLOR & FRANCIS LTD, 2008) Erez, Offer; Romero, Roberto; Espinoza, Jimmy; Fu, Wenjiang; Todem, David; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel; Nien, Jyh Kae; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki Tovi, Shali; Than, Nandor Gabor; Gomez, Ricardo; Hassan, Sonia S.
    Introduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate.
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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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    The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD)
    (WALTER DE GRUYTER GMBH, 2010) Kim, Sun Kwon; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi; Mazaki Tovi, Shali; Gotsch, Francesca; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Pacora, Percy; Ogge, Giovanna; Gomez, Ricardo; Yoon, Bo Hyun; Yeo, Lami; Lamont, Ronald F.; Hassan, Sonia S.
    Objective: Intrauterine devices (IUDs) are used for contraception worldwide; however, the management of pregnancies with an IUD poses a clinical challenge. The purpose of this study was to determine the outcome of pregnancy in patients with an IUD.
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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
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    Tissue factor and tissue pathway inhibitor: A link between a hemostatic disorder and preterm PROM?
    (2006) Erez, Offer; Espinoza, Jimmy; Chatworapongsa, Tinnakorn; Gotsch, Francesca; Kusanovic, Juan Pedro; Than, Nandor Gabor; Mazaki-Tovi, Shali; Papp, Zoltan; Yoon, Bo Hyun; Hoppensteadt, Debra; Fareed, Jawed; Hassan, Sonia; Romero, Roberto