30 results on '"Ogge, Giovanna"'
Search Results
2. Maternal plasma retinol binding protein 4 in acute pyelonephritis during pregnancy
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Vaisbuch, Edi, Romero, Roberto, Mazaki-Tovi, Shali, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Dong, Zhong, Kim, Sun Kwon, Ogge, Giovanna, Gervasi, Maria Teresa, and Hassan, Sonia S.
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- 2010
3. Hyperresistinemia – a Novel Feature in Systemic Infection During Human Pregnancy
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Mazaki-Tovi, Shali, Vaisbuch, Edi, Romero, Roberto, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Kim, Sun Kwon, Ogge, Giovanna, Yoon, Bo Hyun, Dong, Zhong, Gonzalez, Juan M., Gervasi, Maria Teresa, and Hassan, Sonia S.
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- 2010
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4. Activation of the Alternative Pathway of Complement is a Feature of Pre-Term Parturition but not of Spontaneous Labor at Term
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Vaisbuch, Edi, Romero, Roberto, Erez, Offer, Mazaki-Tovi, Shali, Kusanovic, Juan Pedro, Soto, Eleazar, Dong, Zhong, Chaiworapongsa, Tinnakorn, Kim, Sun Kwon, Ogge, Giovanna, Pacora, Percy, Yeo, Lami, and Hassan, Sonia S.
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- 2010
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5. Maternal Plasma Concentration of the Pro-Inflammatory Adipokine Pre-B-Cell-Enhancing Factor (PBEF)/Visfatin Is Elevated In Pregnant Patients with Acute Pyelonephritis
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Mazaki-Tovi, Shali, Vaisbuch, Edi, Romero, Roberto, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Kim, Sun Kwon, Nhan-Chang, Chia-Ling, Gomez, Ricardo, Yoon, Bo H., Yeo, Lami, Mittal, Pooja, Ogge, Giovanna, Gonzalez, Juan M., and Hassan, Sonia S.
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- 2010
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6. Pentraxin 3 in amniotic fluid: a novel association with intra-amniotic infection and inflammation
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Cruciani, Laura, Romero, Roberto, Vaisbuch, Edi, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Mazaki-Tovi, Shali, Mittal, Pooja, Ogge, Giovanna, Gotsch, Francesca, Erez, Offer, Kim, Sun Kwon, Dong, Zhong, Pacora, Percy, Lament, Ronald F., Yeo, Lami, Hassan, Sonia S., and Di Renzo, Gian Carlo
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- 2010
7. Low circulating maternal adiponectin in patients with pyelonephritis: adiponectin at the crossroads of pregnancy and infection
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Mazaki-Tovi, Shali, Romero, Roberto, Vaisbuch, Edi, Chaiworapongsa, Tinnakorn, Erez, Offer, Mittal, Pooja, Kim, Sun Kwon, Gotsch, Francesca, Lament, Ronald, Ogge, Giovanna, Pacora, Percy, Goncalves, Luis, Kim, Chong Jai, Gomez, Ricardo, Espinoza, Jimmy, Hassan, Sonia S., and Kusanovic, Juan Pedro
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- 2010
8. Evidence for intersection between the angiogenic and inflammatory pathways in preterm labor and preterm PROM: 73
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Kim, Sun Kwon, Romero, Roberto, Chaiworapongsa, Tinnakorn, Kusanovic, Juan Pedro, Mazaki-Tovi, Shali, Vaisbuch, Edi, Mittal, Pooja, Ogge, Giovanna, Alpay-Savasan, Zeynep, Madan, Ichchha, Dong, Zhong, Yeo, Lami, and Hassan, Sonia S.
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- 2009
9. Fetal monitoring indications for delivery and 2-year outcome in 310 infants with fetal growth restriction delivered before 32 weeks' gestation in the TRUFFLE study
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Visser, G.H.A., Bilardo, Caterina M., Derks, J. B., Ferrazzi, E., Fratelli, Nicola, Frusca, T., Ganzevoort, W., Lees, Christoph C., Napolitano, Raffaele, Todros, T., Wolf, H., Hecher, K., Marlow, N., Arabin, B., Brezinka, C., Diemert, A., Duvekot, Johannes J., Martinelli, P., Ostermayer, E., Papageorghiou, Aris T., Schlembach, D., Schneider, K. T M, Thilaganathan, B., Valcamonico, A., Aktas, Ayse, Borgione, Silvia, Chaoui, Rabih, Cornette, Jerome M J, Diehl, Thilo, van Eyck, J., van Haastert, I. C., Kingdom, J.C., Lobmaier, Silvia, Lopriore, E., Missfelder-Lobos, Hannah, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Marsal, K., Maurer-Fellbaum, Ute, Mensing van Charante, N., Mulder-De Tollenaer, Susanne, Oberto, Manuela, Oepkes, D., Ogge, Giovanna, van der Post, Joris A. M., Prefumo, Federico, Preston, Lucy, Raimondi, Francesco, and Rattue, H.
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ductus venosus ,fetal growth restriction ,Radiological and Ultrasound Technology ,Reproductive Medicine ,Radiology Nuclear Medicine and imaging ,Obstetrics and Gynaecology ,Journal Article ,cardiotocography ,preterm delivery ,fetal heart rate variation - Abstract
Objective: In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals. Methods: We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery. Results: Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to infants delivered because of FHR decelerations in the safety-net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significantly higher intact survival. Conclusions: In this subanalysis of infants delivered before 32 weeks, the majority were delivered for reasons other than the allocated monitoring strategy indication. Since, in the DV group, CTG-STV criteria were used as a safety net but in the CTG-STV group, no DV safety-net criteria were applied, we speculate that the slightly poorer outcome in the CTG-STV group might be explained by the absence of DV data. The optimal timing of delivery of fetuses with early intrauterine growth restriction may therefore be best determined by monitoring them longitudinally, with both DV and CTG monitoring.
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- 2017
10. Longitudinal study of computerized cardiotocography in early fetal growth restriction
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Wolf, H., Arabin, B., Lees, Christoph C., Oepkes, D., Prefumo, Federico, Thilaganathan, B., Todros, T., Visser, G.H.A., Bilardo, Caterina M., Derks, J. B., Diemert, A., Duvekot, Johannes J., Ferrazzi, E., Frusca, T., Hecher, K., Marlow, N., Martinelli, P., Ostermayer, E., Papageorghiou, Aris T., Scheepers, Hubertina C. J., Schlembach, D., Schneider, K. T M, Valcamonico, A., van Wassenaer-Leemhuis, A., Ganzevoort, W., Aktas, Ayse, Borgione, Silvia, Brezinka, Christoph, Calvert, Sandra, Chaoui, Rabih, Cornette, Jerome M J, Diehl, Thilo, van Eyck, Jim, Fratelli, Nicola, van Haastert, Inge Lot, Johnson, Samantha, Lobmaier, Silvia, Lopriore, Enrico, Mansi, Giuseppina, Missfelder-Lobos, Hannah, Martelli, Paola, Maso, Gianpaolo, Maurer-Fellbaum, Ute, Van Charante, Nico Mensing, De Tollenaer, Susanne Mulder, Moore, Tamanna, Napolitano, Raffaele, Oberto, Manuela, Ogge, Giovanna, and Schuit, Ewoud
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ductus venosus ,fetal growth restriction ,Radiological and Ultrasound Technology ,Reproductive Medicine ,Radiology Nuclear Medicine and imaging ,fetal monitoring ,short-term variation ,Obstetrics and Gynaecology ,Journal Article ,cardiotocography ,preterm - Abstract
Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome. Methods: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome. Results: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2–7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4–7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes. Conclusion: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range.
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- 2017
11. How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks : post-hoc analysis of TRUFFLE study
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Ganzevoort, W., Mensing van Charante, N., Thilaganathan, B., Prefumo, Federico, Arabin, B., Bilardo, Caterina M., Brezinka, C., Derks, J. B., Diemert, A., Duvekot, Johannes J., Ferrazzi, E., Frusca, T., Hecher, K., Marlow, N., Martinelli, P., Ostermayer, E., Papageorghiou, Aris T., Schlembach, D., Schneider, K. T M, Todros, T., Valcamonico, A., Visser, G. H.A., van Wassenaer-Leemhuis, A., Lees, Christoph C., Wolf, H., Aktas, Ayse, Borgione, Silvia, Chaoui, Rabih, Cornette, Jerome M J, Diehl, Thilo, van Eyck, J., Fratelli, Nicola, van Haastert, I. C., Lobmaier, Silvia, Lopriore, E., Missfelder-Lobos, Hannah, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Maurer-Fellbaum, Ute, Mulder-De Tollenaer, Susanne, Napolitano, Raffaele, Oberto, Manuela, Oepkes, D., Ogge, Giovanna, van der Post, Joris A. M., Preston, Lucy, Raimondi, Francesco, Rattue, H., Reiss, Irwin K M, and on behalf of the TRUFFLE Group
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ductus venosus ,fetal growth restriction ,intrauterine growth restriction ,Radiological and Ultrasound Technology ,Reproductive Medicine ,Radiology Nuclear Medicine and imaging ,Obstetrics and Gynaecology ,Journal Article ,cardiotocography - Abstract
Objectives: In the recent TRUFFLE study, it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks' gestation, monitoring of the fetal ductus venosus (DV) waveform combined with computed cardiotocography (CTG) to determine timing of delivery increased the chance of infant survival without neurological impairment. However, concerns with the interpretation were raised, as DV monitoring appeared to be associated with a non-significant increase in fetal death, and some infants were delivered after 32 weeks, at which time the study protocol no longer applied. This secondary sensitivity analysis of the TRUFFLE study focuses on women who delivered before 32 completed weeks' gestation and analyzes in detail the cases of fetal death. Methods: Monitoring data of 317 pregnancies with FGR that delivered before 32 weeks were analyzed, excluding those with absent outcome data or inevitable perinatal death. Women were allocated randomly to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate short-term variation (STV) on CTG; (2) early changes in fetal DV waveform; and (3) late changes in fetal DV waveform. Primary outcome was 2-year survival without neurological impairment. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. Results: Two-year survival without neurological impairment occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however, the difference was not statistically significant (P = 0.21). Among the surviving infants in the DV groups, 93% were free of neurological impairment vs 85% of surviving infants in the CTG-STV group (P = 0.049). All fetal deaths (n = 7) occurred in the groups with DV monitoring. Of the monitoring parameters obtained shortly before fetal death in these seven cases, an abnormal CTG was observed in only one case. Multivariable regression analysis of factors at study entry demonstrated that a later gestational age, higher estimated fetal weight-to-50th percentile ratio and lower umbilical artery pulsatility index (PI)/fetal middle cerebral artery-PI ratio were significantly associated with normal outcome. Allocation to DV monitoring had a smaller effect on outcome, but remained in the model (P < 0.1). Abnormal fetal arterial Doppler before delivery was significantly associated with adverse outcome in the CTG-STV group. In contrast, abnormal DV flow was the only monitoring parameter associated with adverse outcome in the DV groups, while fetal arterial Doppler, STV below the cut-off used in the CTG-STV group and recurrent decelerations in fetal heart rate were not. Conclusions: In accordance with the findings of the TRUFFLE study on monitoring and intervention management of very preterm FGR, we found that the proportion of infants surviving without neuroimpairment was not significantly different when the decision for delivery was based on changes in DV waveform vs reduced STV on CTG. The uneven distribution of fetal deaths towards the DV groups was probably a chance effect, and neurological outcome was better among surviving children in these groups. Before 32 weeks, delaying delivery until abnormalities in DV-PI or STV and/or recurrent decelerations in fetal heat rate occur, as defined by the study protocol, is likely to be safe and possibly benefits long-term outcome.
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- 2017
12. 2 Year Neurodevelopmental and Intermediate Perinatal Outcomes in Infants With Very Preterm Fetal Growth Restriction (TRUFFLE): A Randomised Trial
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Lees, Christoph C., Marlow, Neil, Van Wassenaer-Leemhuis, Aleid, Arabin, Birgit, Bilardo, Caterina M., Brezinka, Christoph, Calvert, Sandra, Derks, Jan B., Diemert, Anke, Duvekot, Johannes J., Ferrazzi, Enrico, Frusca, Tiziana, Ganzevoort, Wessel, Hecher, Kurt, Martinelli, Pasquale, Ostermayer, Eva, Papageorghiou, Aris T., Schlembach, Dietmar, Schneider, K. T M, Thilaganathan, Baskaran, Todros, Tullia, Valcamonico, Adriana, Visser, Gerard H A, Wolf, Hans, Aktas, Ayse, Borgione, Silvia, Chaoui, Rabih, Cornette, Jerome M J, Diehl, Thilo, Van Eyck, Jim, Fratelli, Nicola, Van Haastert, Inge Lot, Lobmaier, Silvia, Lopriore, Enrico, Missfelder-Lobos, Hannah, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Maurer-Fellbaum, Ute, Van Charante, Nico Mensing, De Tollenaer, Susanne Mulder, Napolitano, Raffaele, Oberto, Manuela, Oepkes, Dick, Ogge, Giovanna, Van Der Post, Joris, Prefumo, Federico, Preston, Lucy, Raimondi, Francesco, Reiss, Irwin K M, Scheepers, H. C J, Schuit, Ewoud, Skabar, Aldo, Spaanderman, Marc, Weisglas-Kuperus, Nynke, Zimmermann, Andrea, Moore, Tamanna, Johnson, Samantha, Rigano, Serena, Other Research, Neonatology, Other departments, Amsterdam Public Health, Obstetrics and Gynaecology, Obstetrics and gynaecology, Reproductive Origins of Adult Health and Disease (ROAHD), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), APH - Amsterdam Public Health, ARD - Amsterdam Reproduction and Development, Christoph C., Lee, Neil, Marlow, Aleid van Wassenaer, Leemhui, Birgit, Arabin, Caterina M., Bilardo, Christoph, Brezinka, Sandra, Calvert, Jan B., Derk, Anke, Diemert, Johannes J., Duvekot, Enrico, Ferrazzi, Tiziana, Frusca, Wessel, Ganzevoort, Kurt, Hecher, Martinelli, Pasquale, Eva, Ostermayer, Aris T., Papageorghiou, Dietmar, Schlembach, K. T. M., Schneider, Baskaran, Thilaganathan, Tullia, Todro, Adriana, Valcamonico, Gerard H. A., Visser, Hans, Wolf, for the TRUFFLE study, group, Borgione, Silvia, Fratelli, Nicola, Lobmaier, Silvia, Lopriore, Enrico, Mansi, Giuseppina, Martelli, Paola, Maso, Gianpaolo, Napolitano, Raffaele, Oberto, Manuela, Prefumo, Federico, Raimondi, Francesco, Rigano, Serena, and Obstetrics & Gynecology
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Male ,Percentile ,Pediatrics ,Cardiotocography ,CHILDREN ,Umbilical Arteries ,law.invention ,Primary outcome ,Randomized controlled trial ,Heart Rate ,law ,Central Nervous System Diseases ,Pregnancy ,Fetal growth ,Clinical endpoint ,Prenatal ,GESTATION ,Child ,PREDICTORS ,Non-U.S. Gov't ,Ultrasonography ,Medicine(all) ,Fetal Growth Retardation ,medicine.diagnostic_test ,Medicine (all) ,Research Support, Non-U.S. Gov't ,Pregnancy Outcome ,Obstetrics and Gynecology ,Gestational age ,Pulsed ,General Medicine ,Heart Rate, Fetal ,Very preterm ,Neonatal morbidity ,DOPPLER ,Europe ,Multicenter Study ,PREECLAMPSIA ,Ultrasonography, Doppler, Pulsed ,Child, Preschool ,Infant, Extremely Premature ,Randomized Controlled Trial ,Gestation ,Female ,Gestational Age ,Humans ,Infant, Newborn ,Ultrasonography, Prenatal ,INTERVENTION ,Ductus venosus ,Human ,Reversed flow ,medicine.medical_specialty ,Extremely Premature ,Research Support ,PARAMETERS ,Fetal ,AGE ,HEART-RATE VARIATION ,SDG 3 - Good Health and Well-being ,medicine ,Journal Article ,Preschool ,Fetus ,Intention-to-treat analysis ,business.industry ,RETARDED FETUSES ,Infant ,Newborn ,medicine.disease ,Umbilical Arterie ,Central Nervous System Disease ,business - Abstract
No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV). In this prospective, European multicentre, unblinded, randomised study, we included women with singleton fetuses at 26-32 weeks of gestation who had very preterm fetal growth restriction (ie, low abdominal circumference [ 95th percentile]). We randomly allocated women 1:1:1, with randomly sized blocks and stratified by participating centre and gestational age ( 95th percentile; DV p95), or late DV changes (A wave [the deflection within the venous waveform signifying atrial contraction] at or below baseline; DV no A). The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley III developmental score of less than 85, at 2 years of age. We assessed outcomes in surviving infants with known outcomes at 2 years. We did an intention to treat study for all participants for whom we had data. Safety outcomes were deaths in utero and neonatal deaths and were assessed in all randomly allocated women. This study is registered with ISRCTN, number 56204499. Between Jan 1, 2005 and Oct 1, 2010, 503 of 542 eligible women were randomly allocated to monitoring groups (166 to CTG STV, 167 to DV p95, and 170 to DV no A). The median gestational age at delivery was 30·7 weeks (IQR 29·1-32·1) and mean birthweight was 1019 g (SD 322). The proportion of infants surviving without neuroimpairment did not differ between the CTG STV (111 [77%] of 144 infants with known outcome), DV p95 (119 [84%] of 142), and DV no A (133 [85%] of 157) groups (ptrend=0·09). 12 fetuses (2%) died in utero and 27 (6%) neonatal deaths occurred. Of survivors, more infants where women were randomly assigned to delivery according to late ductus changes (133 [95%] of 140, 95%, 95% CI 90-98) were free of neuroimpairment when compared with those randomly assigned to CTG (111 [85%] of 131, 95% CI 78-90; p=0.005), but this was accompanied by a non-significant increase in perinatal and infant mortality. Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint, timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age. ZonMw, The Netherlands and Dr Hans Ludwig Geisenhofer Foundation, Germany
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- 2015
13. Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE)
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Lees, C, Marlow, N, Arabin, B, Bilardo, Cm, Brezinka, C, Derks, Jb, Duvekot, J, Frusca, T, Diemert, A, Ferrazzi, E, Ganzevoort, W, Hecher, K, Martinelli, P, Ostermayer, E, Papageorghiou, At, Schlembach, D, Schneider, Kt, Thilaganathan, B, Todros, Tullia, van Wassenaer Leemhuis, A, Valcamonico, A, Visser, Gh, Wolf, H, on behalf of the TRUFFLE Group##The TRUFFLE Group collaborating authors include: Missfelder Lobos, H, van Eyck, J, Oepkes, D, Fratelli, N, Prefumo, F, Napolitano, R, Chaoui, R, Maso, G, Ogge', Giovanna, Oberto, Manuela, and van Charante NM
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Perinatal mortality ,Perinatal morbidity ,Fetal Growth Restriction - Published
- 2013
14. Intrauterine growth restriction: oxygen and placental growth
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Ogge', Giovanna, Piccoli, Ettore, Cetin, I., Radaelli, T., Bulfamante, G., and Todros, Tullia
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- 2002
15. Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion.
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Soto, Eleazar, Romero, Roberto, Kusanovic, Juan Pedro, Ogge, Giovanna, Hussein, Youssef, Yeo, Lami, Hassan, Sonia S, Kim, Chong Jai, and Chaiworapongsa, Tinnakorn
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PREECLAMPSIA ,PLACENTAL growth factor ,ENZYME-linked immunosorbent assay ,VASCULAR endothelial growth factors ,ENDOGLIN - Abstract
Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p < 0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p < 0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE. [ABSTRACT FROM AUTHOR]
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- 2012
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16. 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.
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Chaiworapongsa, Tinnakorn, Romero, Roberto, Savasan, Zeynep Alpay, Kusanovic, Juan Pedro, Ogge, Giovanna, Soto, Eleazar, Dong, Zhong, Tarca, Adi, Gaurav, Bhatti, and Hassan, Sonia S.
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VASCULAR endothelial growth factors ,PREECLAMPSIA ,CHILDBIRTH ,MICROBIOLOGICAL assay ,LOGISTIC regression analysis ,SURVIVAL analysis (Biometry) - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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17. An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study.
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Romero, Roberto, Chaiworapongsa, Tinnakorn, Erez, Offer, Tarca, Adi L., Gervasi, Maria Teresa, Kusanovic, Juan Pedro, Mittal, Pooja, Ogge, Giovanna, Vaisbuch, Edi, Mazaki-Tovi, Shali, Dong, Zhong, Kim, Sun Kwon, Yeo, Lami, and Hassan, Sonia S.
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VASCULAR endothelial growth factors ,FETAL death ,LONGITUDINAL method ,HIGH-risk pregnancy ,MATERNAL health ,DIAGNOSIS of placenta diseases ,GESTATIONAL age - Abstract
Objective. Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF). Methods. This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age ( n = 124); and (2) patients who had a fetal death ( n = 19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis. Results. (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates ( p < 0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation ( p < 0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation ( p = 0.04) and became higher than those of controls between 20 and 40 weeks of gestation ( p < 0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation ( p < 0.05); (5) The ratio of PlGF/(sVEGFR-1 × sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation ( p < 0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation. Conclusions. Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters. [ABSTRACT FROM AUTHOR]
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- 2010
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18. Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM, but not with intra-amniotic infection/inflammation.
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Cruciani, Laura, Romero, Roberto, Vaisbuch, Edi, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Mazaki-Tovi, Shali, Dong, Zhong, Kim, Sun Kwon, Ogge, Giovanna, Yeo, Lami, Mittal, Pooja, and Hassan, Sonia S.
- Subjects
AMNIOCENTESIS ,IMMUNOREGULATION ,PREGNANT women ,RISK factors in premature labor ,PREGNANCY complication risk factors ,FETAL membrane abnormalities - Abstract
Objective. Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM). Study design. This cross-sectional study included women in the following groups: (1) nonpregnant ( n = 40); (2) uncomplicated pregnancies in the first ( n = 22), second ( n = 22) or third trimester ( n = 71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor ( n = 49); (4) PTL and intact membranes who delivered at term ( n = 49); (5) PTL without IAI who delivered preterm ( n = 26); (6) PTL with IAI ( n = 65); (7) preterm PROM without IAI ( n = 25); and (8) preterm PROM with IAI ( n = 77). Maternal plasma PTX3 concentrations were determined by ELISA. Results. (1) Maternal plasma PTX3 concentrations increased with advancing gestational age ( r = 0.62, p < 0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29 ng/ml vs. 5.98 ng/ml, p = 0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women ( p < 0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women ( p < 0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations. Conclusions. The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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19. Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate.
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Mazaki-Tovi, Shali, Vaisbuch, Edi, Romero, Roberto, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Kim, Sun Kwon, Nhan-Chang, Chia-Ling, Gomez, Ricardo, Alpay Savasan, Zeynep, Madan, Ichchha, Yoon, Bo Hyun, Yeo, Lami, Mittal, Pooja, Ogge, Giovanna, Gonzalez, Juan M., and Hassan, Sonia S.
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PREECLAMPSIA ,PREGNANT women ,CORD blood ,NEWBORN infants ,PREMATURE infants ,ENZYME-linked immunosorbent assay ,PATIENTS - Abstract
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. Study design. This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups ( p < 0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group ( r = 0.48, p = 0.04). Conclusion. Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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20. Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments.
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Chaiworapongsa, Tinnakorn, Kusanovic, Juan Pedro, Savasan, Zeynep Alpay, Mazaki-Tovi, Shali, Kim, Sun Kwon, Vaisbuch, Edi, Tarca, Adi L., Mittal, Pooja, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, Hassan, Sonia S., and Romero, Roberto
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FETAL death ,VASCULAR endothelial growth factors ,CYTOKINES ,PREECLAMPSIA ,MULTIVARIATE analysis - Abstract
Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design. Maternal plasma was obtained from patients with fetal death ( n = 59) and normal pregnant women ( n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term ( n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women ( p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women ( p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4–7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group ( p < 0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5–164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). Conclusion. Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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21. Unexplained fetal death is associated with increased concentrations of anti-angiogenic factors in amniotic fluid.
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Chaiworapongsa, Tinnakorn, Romero, Roberto, Kusanovic, Juan P., Savasan, Zeynep A., Kim, Sun Kwon, Mazaki-Tovi, Shali, Vaisbuch, Edi, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, Mittal, Pooja, and Hassan, Sonia S.
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NEOVASCULARIZATION ,PREECLAMPSIA ,AMNIOTIC fluid embolism ,PREGNANCY complications ,RISK factors in premature labor - Abstract
Objective. Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death ( n = 35) and controls ( n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained ( n = 25); (2) preeclampsia and/or placental abruption ( n = 5); and (3) chromosomal/congenital anomalies ( n = 5). The control group consisted of patients with preterm labor (PTL) who delivered at term ( n = 92) and women at term not in labor ( n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group ( p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth ( p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
22. Evidence in support of a role for anti-angiogenic factors in preterm prelabor rupture of membranes.
- Author
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Savasan, Zeynep Alpay, Romero, Roberto, Chaiworapongsa, Tinnakorn, Kusanovic, Juan Pedro, Kim, Sun Kwon, Mazaki-Tovi, Shali, Vaisbuch, Edi, Mittal, Pooja, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, and Hassan, Sonia S.
- Subjects
PREMATURE labor ,BIOLOGICAL membranes ,VAGINAL diseases ,GESTATIONAL age ,ENZYME-linked immunosorbent assay - Abstract
Objective. Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition. Study design. This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) ( n = 48); (2) preterm labor (PTL) leading to term delivery ( n = 143); (3) PTL resulting in preterm delivery with ( n = 72) and without IAI ( n = 100); (4) preterm PROM with ( n = 46) and without IAI ( n = 42); (5) term in labor ( n = 48); and (6) term not in labor ( n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term ( p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95%CI 1.4–2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 ( p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations ( p > 0.05 for each comparison). Conclusion. (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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23. 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.
- Author
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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., and Rogers, Wade T.
- Subjects
AMNIOTIC liquid ,PREMATURE labor ,PROTEOMICS ,BIOMARKERS ,THYMOSIN - Abstract
Objective. Examination of the amniotic fluid (AF) proteome has been previously attempted to identify useful biomarkers in predicting the outcome of preterm labor (PTL). Isobaric Tag for Relative and Absolute Quantitation (iTRAQ™) labeling allows direct ratiometric comparison of relative abundance of identified protein species among multiplexed samples. The purpose of this study was to apply, for the first time, the combination of iTRAQ and tandem mass spectrometry to identify proteins differentially regulated in AF samples of women with spontaneous PTL and intact membranes with and without intra-amniotic infection/inflammation (IAI). 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. Results. Collectively, 123,011 MS
2 spectra were analyzed, and over 25,000 peptides were analyzed by database search (X!Tandem and Mascot), resulting in the identification of 309 unique high-confidence proteins. Analysis of differentially present iTRAQ reporter peaks revealed many proteins that have been previously reported to be associated with preterm delivery with IAI. Importantly, many novel proteins were found to be up-regulated in the AF of patients with PTL and IAI including leukocyte elastase precursor, Thymosin-like 3, and 14-3-3 protein isoforms. Moreover, we observed differential expression of proteins in AF of patients who delivered preterm in the absence of IAI in comparison with those with PTL who delivered at term including Mimecan precursor, latent-transforming growth factor β-binding protein isoform 1L precursor, and Resistin. These findings have been confirmed for Resistin in an independent cohort of samples using ELISA. Gene ontology enrichment analysis was employed to reveal families of proteins participating in distinct biological processes. We identified enrichment for host defense, anti-apoptosis, metabolism/catabolism and cell and protein mobility, localization and targeting. Conclusions. (1) Proteomics with iTRAQ labeling is a profiling tool capable of revealing differential expression of proteins in AF; (2) We discovered 82 proteins differentially expressed in three clinical subgroups of premature labor, 67 which were heretofore unknown. Of particular importance is the identification of proteins differentially expressed in AF from women who delivered preterm in the absence of IAI. This is the first report of the positive identification of biomarkers in this subgroup of patients. [ABSTRACT FROM AUTHOR]- Published
- 2010
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24. A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study.
- Author
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Chaiworapongsa, Tinnakorn, Romero, Roberto, Tarca, Adi, Kusanovic, Juan Pedro, Mittal, Pooja, Kim, Sun K., Gotsch, Francesca, Erez, Offer, Vaisbuch, Edi, Mazaki-Tovi, Shali, Pacora, Percy, Ogge, Giovanna, Dong, Zhong, Kim, Chong J., Yeo, Lami, and Hassan, Sonia S.
- Subjects
PREMATURE labor ,PREGNANT women ,PREECLAMPSIA ,PREGNANCY complications ,CLINICAL medicine - Abstract
Objective. An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. Study Design. This longitudinal nested case–control study included normal pregnant women ( n = 208) and patients with PTL leading to preterm delivery ( n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to36.9 weeks of gestation. The end point (time of diagnosis) of the study, ‘True PTL’, was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. Results. (1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15–20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5–10 weeks prior to the diagnosis of ‘true PTL’. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of ‘true PTL’; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. Conclusion. The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition. [ABSTRACT FROM AUTHOR]
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- 2009
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25. 805: Serum and plasma determination of angiogenic and anti-angiogenic factors yield different results: the need for standardization in clinical practice
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Ogge, Giovanna, Romero, Roberto, Kusanovic, Juan Pedro, Chaiworapongsa, Tinnakorn, Dong, Zhong, Mittal, Pooja, Vaisbuch, Edi, Mazaki-Tovi, Shali, Gonzalez, Juan, Yeo, Lami, and Hassan, Sonia S.
- Published
- 2009
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26. 792: Fetal death: a condition with a disparity in SVEGFR-2 between the maternal and fetal compartments
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Chaiworapongsa, Tinnakorn, Romero, Roberto, Kusanovic, Juan Pedro, Savasan, Zeynep Alpay, Mazaki-Tovi, Shali, Kim, Sun Kwon, Vaisbuch, Edi, Tarca, Adi L., Mittal, Pooja, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, and Hassan, Sonia S.
- Published
- 2009
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27. 791: Fetal death is associated with increased concentration of anti-angiogenic factors
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Chaiworapongsa, Tinnakorn, Romero, Roberto, Kusanovic, Juan Pedro, Savasan, Zeynep Alpay, Kim, Sun Kwon, Mazaki-Tovi, Shali, Vaibuch, Edi, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, Mittal, Pooja, and Hassan, Sonia S.
- Published
- 2009
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28. 534: Evidence in support for a role of anti-angiogenic factors in preterm prelabor rupture of membranes (PPROM)
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Savasan, Zeynep Alpay, Romero, Roberto, Chaiworapongsa, Tinnakorn, Kusanovic, Juan Pedro, Kim, Sun Kwon, Mazaki-Tovi, Shali, Vaisbuch, Edi, Mittal, Pooja, Ogge, Giovanna, Madan, Ichchha, Dong, Zhong, Yeo, Lami, and Hassan, Sonia S.
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- 2009
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29. 520: Activation of the alternative pathway of complement is a feature of preterm parturition but not of spontaneous labor at term
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Vaisbuch, Edi, Romero, Roberto, Erez, Offer, Mazaki-Tovi, Shali, Kusanovic, Juan Pedro, Soto, Eleazar, Dong, Zhong, Chaiworapongsa, Tinnakorn, Kim, Sun Kwon, Ogge, Giovanna, Pacora, Percy, Yeo, Lami, and Hassan, Sonia S.
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- 2009
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30. 73: Evidence for intersection between the angiogenic and inflammatory pathways in preterm labor and preterm PROM.
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Kim, Sun Kwon, Romero, Roberto, Chaiworapongsa, Tinnakorn, Kusanovic, Juan Pedro, Mazaki-Tovi, Shali, Vaisbuch, Edi, Mittal, Pooja, Ogge, Giovanna, Alpay-Savasan, Zeynep, Madan, Ichchha, Dong, Zhong, Yeo, Lami, and Hassan, Sonia S.
- Published
- 2009
- Full Text
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