Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?
L Myatt, R G Clifton, J M Roberts, C Y Spong, R J Wapner, J M Thorp Jr, B M Mercer, A M Peaceman, S M Ramin, M W Carpenter, A Sciscione, J E Tolosa, G Saade, Y Sorokin, G D Anderson, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, S Caritis, T Kamon, M Cotroneo, D Fischer, M Varner, P Reed, S Quinn, V Morby, F Porter, R Silver, J Miller, K Hill, J Hauth, D J Rouse, A Northen, P Files, J Grant, M Wallace, K Bailey, R Wapner, S Bousleiman, R Alcon, K Saravia, F Loffredo, A Bayless, C Perez, M Lake, M Talucci, K Boggess, K Dorman, J Mitchell, K Clark, S Timlin, J Bailit, C Milluzzi, W Dalton, C Brezine, D Bazzo, K Leveno, J Sheffield, L Moseley, M Santillan, K Buentipo, J Price, L Sherman, C Melton, Y Gloria-McCutchen, B Espino, M Dinsmoor, T Matson-Manning, G Mallett, S Blackwell, K Cannon, S Lege-Humbert, Z Spears, J Tillinghast, M Seebeck, P Samuels, F Johnson, S Fyffe, C Latimer, S Frantz, S Wylie, J Iams, M Talucci, M Hoffman, J Benson, Z Reid, C Tocci, M Harper, P Meis, M Swain, W Smith, L Davis, E Lairson, S Butcher, S Maxwell, D Fisher, J Moss, B Stratton, G Hankins, J Brandon, C Nelson-Becker, G Olson, L Pacheco, G Norman, S Blackwell, P Lockhart, D Driscoll, M Dombrowski, E Thom, T Boekhoudt, L Leuchtenburg, G Pearson, V Pemberton, J Cutler, W Barouch, S Tolivaisa, L Myatt, R G Clifton, J M Roberts, C Y Spong, R J Wapner, J M Thorp Jr, B M Mercer, A M Peaceman, S M Ramin, M W Carpenter, A Sciscione, J E Tolosa, G Saade, Y Sorokin, G D Anderson, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, S Caritis, T Kamon, M Cotroneo, D Fischer, M Varner, P Reed, S Quinn, V Morby, F Porter, R Silver, J Miller, K Hill, J Hauth, D J Rouse, A Northen, P Files, J Grant, M Wallace, K Bailey, R Wapner, S Bousleiman, R Alcon, K Saravia, F Loffredo, A Bayless, C Perez, M Lake, M Talucci, K Boggess, K Dorman, J Mitchell, K Clark, S Timlin, J Bailit, C Milluzzi, W Dalton, C Brezine, D Bazzo, K Leveno, J Sheffield, L Moseley, M Santillan, K Buentipo, J Price, L Sherman, C Melton, Y Gloria-McCutchen, B Espino, M Dinsmoor, T Matson-Manning, G Mallett, S Blackwell, K Cannon, S Lege-Humbert, Z Spears, J Tillinghast, M Seebeck, P Samuels, F Johnson, S Fyffe, C Latimer, S Frantz, S Wylie, J Iams, M Talucci, M Hoffman, J Benson, Z Reid, C Tocci, M Harper, P Meis, M Swain, W Smith, L Davis, E Lairson, S Butcher, S Maxwell, D Fisher, J Moss, B Stratton, G Hankins, J Brandon, C Nelson-Becker, G Olson, L Pacheco, G Norman, S Blackwell, P Lockhart, D Driscoll, M Dombrowski, E Thom, T Boekhoudt, L Leuchtenburg, G Pearson, V Pemberton, J Cutler, W Barouch, S Tolivaisa
Abstract
Objective: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women.
Design: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls.
Setting: A multicentre study in 16 academic medical centres in the USA.
Population: Low-risk nulliparous women.
Methods: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics.
Main outcome measures: Change in PlGF, sFlt-1 and sEng.
Results: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester.
Conclusion: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.
Keywords: Angiogenesis; endoglin; platelet growth factor; pre-eclampsia; sFlt-1.
Conflict of interest statement
Disclosure of interests
None of the authors have a conflict of interest.
© Published 2013 This article is a U.S. Government work and is in the public domain in the USA © 2013 RCOG.
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Source: PubMed