Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies
Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar...
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| Published in | PloS one Vol. 5; no. 10; p. e13263 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
11.10.2010
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1932-6203 1932-6203 |
| DOI | 10.1371/journal.pone.0013263 |
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| Abstract | Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.
This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.
The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.
The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. |
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| AbstractList | Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.BACKGROUNDDifferences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.METHODSThis study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.RESULTSThe odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.CONCLUSIONSThe pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. |
| Author | Clifton, Rebecca G. Landon, Mark Van Dorsten, Peter Jeyabalan, Arun Hauth, John C. Lindheimer, Marshall D. Miodovnik, Menachem Powers, Robert W. Klebanoff, Mark A. Sibai, Baha |
| AuthorAffiliation | 2 The George Washington University Biostatistics Center, Washington, D.C., United States of America 9 Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, Ohio, United States of America 8 Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, Ohio, United States of America 3 Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, United States of America 1 Department of Obstetrics, Gynecology and Women's Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America 5 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America Institute of Zoology, Chinese Academy of Sciences, China 6 Department of Obstetrics and Gynecology, University of Chicago School of Medicine, Chicago, Illinois, United States of America 4 Department of Obstetrics and Gynecology, U |
| AuthorAffiliation_xml | – name: 3 Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, United States of America – name: 9 Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, Ohio, United States of America – name: 2 The George Washington University Biostatistics Center, Washington, D.C., United States of America – name: Institute of Zoology, Chinese Academy of Sciences, China – name: 6 Department of Obstetrics and Gynecology, University of Chicago School of Medicine, Chicago, Illinois, United States of America – name: 7 Department of Obstetrics and Gynecology, University of Tennessee School of Medicine, Memphis, Tennessee, United States of America – name: 1 Department of Obstetrics, Gynecology and Women's Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America – name: 5 Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America – name: 4 Department of Obstetrics and Gynecology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States of America – name: 8 Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, Ohio, United States of America |
| Author_xml | – sequence: 1 givenname: Robert W. surname: Powers fullname: Powers, Robert W. – sequence: 2 givenname: Arun surname: Jeyabalan fullname: Jeyabalan, Arun – sequence: 3 givenname: Rebecca G. surname: Clifton fullname: Clifton, Rebecca G. – sequence: 4 givenname: Peter surname: Van Dorsten fullname: Van Dorsten, Peter – sequence: 5 givenname: John C. surname: Hauth fullname: Hauth, John C. – sequence: 6 givenname: Mark A. surname: Klebanoff fullname: Klebanoff, Mark A. – sequence: 7 givenname: Marshall D. surname: Lindheimer fullname: Lindheimer, Marshall D. – sequence: 8 givenname: Baha surname: Sibai fullname: Sibai, Baha – sequence: 9 givenname: Mark surname: Landon fullname: Landon, Mark – sequence: 10 givenname: Menachem surname: Miodovnik fullname: Miodovnik, Menachem |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20948996$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Contributor | Romero, R Sabo, V Rabello, Y Jones, P Spong, C Kamon, T Iams, J D Elder, N Meadows, S Thom, E Elder, S Swain, M Pemberton, V Brenner, S Collins, B Kuller, J Ramsey, R Yaffe, S Mercer, B Bain, R P Cotroneo, M Goldenberg, R Copper, R Moawad, A H MacPherson, C Mueller, E McCoy, S Newman, R B Norman, G Sorokin, Y Catz, C Fischer, M L Roberts, J M Paul, R Christmas, J T Meier, A Meis, P McNellis, D Carter, S G Johnson, D Thurnau, G Carter, B McCart, D Millinder, A Minton, V Caritis, S |
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| Copyright | 2010. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2010 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: RP. Performed the experiments: RP AJ. Analyzed the data: RP RGC. Wrote the paper: RP AJ RGC PVD JCH MK ML BS ML MM. Membership of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network is provided in the Acknowledgments. |
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| References_xml | – volume: 350 start-page: 672 year: 2004 ident: ref6 article-title: Circulating angiogenic factors and the risk of preeclampsia. publication-title: New England Journal of Medicine doi: 10.1056/NEJMoa031884 – volume: 198 start-page: 200.e201 year: 2008 ident: ref15 article-title: Circulating angiogenic factors in singleton vs multiple-gestation pregnancies. publication-title: American Journal of Obstetrics & Gynecology doi: 10.1016/j.ajog.2007.08.042 – volume: 338 start-page: 701 year: 1998 ident: ref4 article-title: Low-dose aspirin to prevent preeclampsia in women at high risk. 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| Snippet | Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to... Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are... Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are... |
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| SubjectTerms | Adult Angiogenesis Angiogenesis Inducing Agents - blood Antiangiogenics Antigens, CD - blood Aspirin Blood pressure Change detection Childrens health Diabetes Diabetes mellitus Endocrinology Endoglin Female Fetuses Gestation Gestational diabetes Gynecology Humans Hypertension Medical records Medicine Obstetrics Obstetrics/Hypertensive Disorders Obstetrics/Management of High-Risk Pregnancies Obstetrics/Pregnancy Pathogenesis Placenta Placenta Growth Factor Pre-eclampsia Pre-Eclampsia - blood Pre-Eclampsia - diagnosis Preeclampsia Pregnancy Pregnancy Proteins - blood Protein-tyrosine kinase Proteins Receptor, Macrophage Colony-Stimulating Factor - blood Receptors, Cell Surface - blood Risk factors Risk groups Risk management Secondary analysis Studies Tyrosine Vascular endothelial growth factor Womens health |
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| Title | Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/20948996 https://www.proquest.com/docview/1295478713 https://www.proquest.com/docview/759523973 https://pubmed.ncbi.nlm.nih.gov/PMC2952583 https://doaj.org/article/d36e75fb391b417bbdd4aec27e75cef2 http://dx.doi.org/10.1371/journal.pone.0013263 |
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