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Published in: BMC Pregnancy and Childbirth 1/2013

Open Access 01-12-2013 | Research article

Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study

Authors: Attila Molvarec, Nóra Gullai, Balázs Stenczer, Gergely Fügedi, Bálint Nagy, János Rigó Jr

Published in: BMC Pregnancy and Childbirth | Issue 1/2013

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Abstract

Background

Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events.

Methods

Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF≥100 pg/ml), low (12<PlGF<100) or very low (PlGF≤12 pg/ml). A positive test for abnormal fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy.

Results

In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow.

Conclusions

PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography.
Literature
1.
go back to reference National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy: Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000, 183: S1-S22.CrossRef National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy: Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000, 183: S1-S22.CrossRef
3.
go back to reference Gardosi J, Madurasinghe V, Williams M, Malik A, Francis A: Maternal and fetal risk factors for stillbirth: population based study. Brit Med J. 2013, 346: f108-10.1136/bmj.f108.CrossRefPubMedPubMedCentral Gardosi J, Madurasinghe V, Williams M, Malik A, Francis A: Maternal and fetal risk factors for stillbirth: population based study. Brit Med J. 2013, 346: f108-10.1136/bmj.f108.CrossRefPubMedPubMedCentral
4.
go back to reference Knudsen UB, Kronborg CS, von-Dadelszen P, Kupfer K, Lee S-W, Vittinghus E, Allen JG, Redman CW: A single rapid point of care placental growth factor determination as an aid in the diagnosis of preeclampsia. Pregnancy Hypertens. 2012, 2: 8-15.PubMed Knudsen UB, Kronborg CS, von-Dadelszen P, Kupfer K, Lee S-W, Vittinghus E, Allen JG, Redman CW: A single rapid point of care placental growth factor determination as an aid in the diagnosis of preeclampsia. Pregnancy Hypertens. 2012, 2: 8-15.PubMed
5.
go back to reference Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004, 350: 672-683. 10.1056/NEJMoa031884.CrossRefPubMed Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004, 350: 672-683. 10.1056/NEJMoa031884.CrossRefPubMed
6.
go back to reference Hertig A, Berkane N, Lefevre G, Toumi K, Marti HP, Capeau J, Uzan S, Rondeau E: Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004, 50: 1702-1703. 10.1373/clinchem.2004.036715.CrossRefPubMed Hertig A, Berkane N, Lefevre G, Toumi K, Marti HP, Capeau J, Uzan S, Rondeau E: Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004, 50: 1702-1703. 10.1373/clinchem.2004.036715.CrossRefPubMed
7.
go back to reference McKeeman GC, Ardill JE, Caldwell CM, Hunter AJ, McClure N: Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol. 2004, 191: 1240-1246. 10.1016/j.ajog.2004.03.004.CrossRefPubMed McKeeman GC, Ardill JE, Caldwell CM, Hunter AJ, McClure N: Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol. 2004, 191: 1240-1246. 10.1016/j.ajog.2004.03.004.CrossRefPubMed
8.
go back to reference Shibata E, Rajakumar A, Powers RW, Larkin RW, Gilmour C, Bodnar LM, Crombleholme WR, Ness RB, Roberts JM, Hubel CA: Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor. J Clin Endocrinol Metab. 2005, 90: 4895-4903. 10.1210/jc.2004-1955.CrossRefPubMed Shibata E, Rajakumar A, Powers RW, Larkin RW, Gilmour C, Bodnar LM, Crombleholme WR, Ness RB, Roberts JM, Hubel CA: Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor. J Clin Endocrinol Metab. 2005, 90: 4895-4903. 10.1210/jc.2004-1955.CrossRefPubMed
9.
go back to reference Kim SY, Ryu HM, Yang JH, Kim MY, Han JY, Kim JO, Chung JH, Park SY, Lee MH, Kim DJ: Increased sFlt-1 to PlGF ratio in women who subsequently develop preeclampsia. J Korean Med Sci. 2007, 22: 873-877. 10.3346/jkms.2007.22.5.873.CrossRefPubMedPubMedCentral Kim SY, Ryu HM, Yang JH, Kim MY, Han JY, Kim JO, Chung JH, Park SY, Lee MH, Kim DJ: Increased sFlt-1 to PlGF ratio in women who subsequently develop preeclampsia. J Korean Med Sci. 2007, 22: 873-877. 10.3346/jkms.2007.22.5.873.CrossRefPubMedPubMedCentral
10.
go back to reference Torry DS, Wang HS, Wang TH, Caudle MR, Torry RJ: Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol. 1998, 179: 1539-1544. 10.1016/S0002-9378(98)70021-3.CrossRefPubMed Torry DS, Wang HS, Wang TH, Caudle MR, Torry RJ: Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol. 1998, 179: 1539-1544. 10.1016/S0002-9378(98)70021-3.CrossRefPubMed
11.
go back to reference Taylor RN, Grimwood J, Taylor RS, McMaster MT, Fisher SJ, North RA: Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol. 2003, 188: 177-182. 10.1067/mob.2003.111.CrossRefPubMed Taylor RN, Grimwood J, Taylor RS, McMaster MT, Fisher SJ, North RA: Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol. 2003, 188: 177-182. 10.1067/mob.2003.111.CrossRefPubMed
12.
go back to reference Reuvekamp A, Velsing-Aarts FV, Poulina IE, Capello JJ, Duits AJ: Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia. Br J Obstet Gynaecol. 1999, 106: 1019-1022. 10.1111/j.1471-0528.1999.tb08107.x.CrossRefPubMed Reuvekamp A, Velsing-Aarts FV, Poulina IE, Capello JJ, Duits AJ: Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia. Br J Obstet Gynaecol. 1999, 106: 1019-1022. 10.1111/j.1471-0528.1999.tb08107.x.CrossRefPubMed
13.
go back to reference Livingston JC, Chin R, Haddad B, McKinney ET, Ahokas R, Sibai BM: Reductions of vascular endothelial growth factor and placental growth factor concentrations in severe preeclampsia. Am J Obstet Gynecol. 2000, 183: 1554-1557. 10.1067/mob.2000.108022.CrossRefPubMed Livingston JC, Chin R, Haddad B, McKinney ET, Ahokas R, Sibai BM: Reductions of vascular endothelial growth factor and placental growth factor concentrations in severe preeclampsia. Am J Obstet Gynecol. 2000, 183: 1554-1557. 10.1067/mob.2000.108022.CrossRefPubMed
14.
go back to reference Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C: Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol. 2010, 202:40: e1-7. Sunderji S, Gaziano E, Wothe D, Rogers LC, Sibai B, Karumanchi SA, Hodges-Savola C: Automated assays for sVEGF R1 and PlGF as an aid in the diagnosis of preterm preeclampsia: a prospective clinical study. Am J Obstet Gynecol. 2010, 202:40: e1-7.
15.
go back to reference De-Vivo A, Baviera G, Giordano D, Todarello G, Corrado F, D’Anna R: Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia. Acta Obstet Gynecol Scand. 2008, 87: 837-842. 10.1080/00016340802253759.CrossRefPubMed De-Vivo A, Baviera G, Giordano D, Todarello G, Corrado F, D’Anna R: Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia. Acta Obstet Gynecol Scand. 2008, 87: 837-842. 10.1080/00016340802253759.CrossRefPubMed
16.
go back to reference Ohkuchi A, Hirashima C, Suzuki H, Takahashi K, Yoshida M, Matsubara S, Suzuki M: Evaluation of a new and automated electrochemiluminescence immunoassay for plasma sFlt-1 and PlGF levels in women with preeclampsia. Hypertens Res. 2010, 33: 422-427. 10.1038/hr.2010.15.CrossRefPubMed Ohkuchi A, Hirashima C, Suzuki H, Takahashi K, Yoshida M, Matsubara S, Suzuki M: Evaluation of a new and automated electrochemiluminescence immunoassay for plasma sFlt-1 and PlGF levels in women with preeclampsia. Hypertens Res. 2010, 33: 422-427. 10.1038/hr.2010.15.CrossRefPubMed
17.
go back to reference Kusanovic JP, Romero R, Chaiworapongsa T, Erez O, Mittal P, Vaisbuch E, Mazaki-Tovi S, Gotsch F, Edwin SS, Gomez R, Yeo L, Conde-Agudelo A, Hassan SS: A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. J Matern Fetal Neonatal Med. 2009, 22: 1021-1038. 10.3109/14767050902994754.CrossRefPubMedPubMedCentral Kusanovic JP, Romero R, Chaiworapongsa T, Erez O, Mittal P, Vaisbuch E, Mazaki-Tovi S, Gotsch F, Edwin SS, Gomez R, Yeo L, Conde-Agudelo A, Hassan SS: A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. J Matern Fetal Neonatal Med. 2009, 22: 1021-1038. 10.3109/14767050902994754.CrossRefPubMedPubMedCentral
18.
go back to reference Lim JH, Kim SY, Park SY, Yang JH, Kim MY, Ryu HM: Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors. Obstet Gynecol. 2008, 111: 1403-1409. 10.1097/AOG.0b013e3181719b7a.CrossRefPubMed Lim JH, Kim SY, Park SY, Yang JH, Kim MY, Ryu HM: Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors. Obstet Gynecol. 2008, 111: 1403-1409. 10.1097/AOG.0b013e3181719b7a.CrossRefPubMed
19.
go back to reference Molvarec A, Szarka A, Walentin S, Szucs E, Nagy B, Rigo J: Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia. Hypertens Res. 2010, 33: 892-898. 10.1038/hr.2010.92.CrossRefPubMed Molvarec A, Szarka A, Walentin S, Szucs E, Nagy B, Rigo J: Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia. Hypertens Res. 2010, 33: 892-898. 10.1038/hr.2010.92.CrossRefPubMed
20.
go back to reference Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, Pape J, Dudenhausen JW, Denk B, Stepan H: An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010, 202:161: e1-11. Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, Pape J, Dudenhausen JW, Denk B, Stepan H: An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010, 202:161: e1-11.
21.
go back to reference Powers RW, Jeyabalan A, Clifton RG, Van-Dorsten P, Hauth JC, Klebanoff MA, Lindheimer MD, Sibai B, Landon M, Miodovnik M, Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network: Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One. 2010, 5: e13263-10.1371/journal.pone.0013263.CrossRefPubMedPubMedCentral Powers RW, Jeyabalan A, Clifton RG, Van-Dorsten P, Hauth JC, Klebanoff MA, Lindheimer MD, Sibai B, Landon M, Miodovnik M, Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network: Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One. 2010, 5: e13263-10.1371/journal.pone.0013263.CrossRefPubMedPubMedCentral
22.
go back to reference Nadarajah VD, Min RG, Judson JP, Jegasothy R, Ling EH: Maternal plasma soluble fms-like tyrosine kinase-1 and placental growth factor levels as biochemical markers of gestational hypertension for Malaysian mothers. J Obstet Gynaecol Res. 2009, 35: 855-863. 10.1111/j.1447-0756.2009.01037.x.CrossRefPubMed Nadarajah VD, Min RG, Judson JP, Jegasothy R, Ling EH: Maternal plasma soluble fms-like tyrosine kinase-1 and placental growth factor levels as biochemical markers of gestational hypertension for Malaysian mothers. J Obstet Gynaecol Res. 2009, 35: 855-863. 10.1111/j.1447-0756.2009.01037.x.CrossRefPubMed
23.
go back to reference Khalil A, Muttukrishna S, Harrington K, Jauniaux E: Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PLoS One. 2008, 3: e2766-10.1371/journal.pone.0002766.CrossRefPubMedPubMedCentral Khalil A, Muttukrishna S, Harrington K, Jauniaux E: Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PLoS One. 2008, 3: e2766-10.1371/journal.pone.0002766.CrossRefPubMedPubMedCentral
24.
go back to reference Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H: The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012, 206:58: e1-8. Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, Denk B, Stepan H: The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012, 206:58: e1-8.
25.
go back to reference Gullai N, Stenczer B, Molvarec A, Fugedi G, Veresh Z, Nagy B, Rigo J: Evaluation of a rapid and simple placental growth factor test in hypertensive disorders of pregnancy. Hypertens Res. 2013, 36: 457-462. 10.1038/hr.2012.206.CrossRefPubMed Gullai N, Stenczer B, Molvarec A, Fugedi G, Veresh Z, Nagy B, Rigo J: Evaluation of a rapid and simple placental growth factor test in hypertensive disorders of pregnancy. Hypertens Res. 2013, 36: 457-462. 10.1038/hr.2012.206.CrossRefPubMed
26.
go back to reference Chaiworapongsa T, Romero R, Korzeniewski SJ, Cortez JM, Pappas A, Tarca AL, Chaemsaithong P, Dong Z, Yeo L, Hassan SS: Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study. J Matern Fetal Neonatal Med. in press. http://dx.doi.org/10.3109/14767058.2013.806905 Chaiworapongsa T, Romero R, Korzeniewski SJ, Cortez JM, Pappas A, Tarca AL, Chaemsaithong P, Dong Z, Yeo L, Hassan SS: Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study. J Matern Fetal Neonatal Med. in press. http://​dx.​doi.​org/​10.​3109/​14767058.​2013.​806905
27.
go back to reference Saffer C, Olson G, Boggess KA, Beyerlein R, Eubank C, Sibai BM, the NORMALS Study Group: Determination of placental growth factor (PlGF) levels in healthy pregnant women without signs or symptoms of preeclampsia. Pregnancy Hypertens. 2013, 3: 124-132.PubMed Saffer C, Olson G, Boggess KA, Beyerlein R, Eubank C, Sibai BM, the NORMALS Study Group: Determination of placental growth factor (PlGF) levels in healthy pregnant women without signs or symptoms of preeclampsia. Pregnancy Hypertens. 2013, 3: 124-132.PubMed
28.
go back to reference Benton SJ, Hu Y, Xie F, Kupfer K, Lee SW, Magee LA, von-Dadelszen P: Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction?. Am J Obstet Gynecol. 2012, 206:163: e1-7. Benton SJ, Hu Y, Xie F, Kupfer K, Lee SW, Magee LA, von-Dadelszen P: Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction?. Am J Obstet Gynecol. 2012, 206:163: e1-7.
29.
go back to reference Schlembach D, Wallner W, Sengenberger R, Stiegler E, Mortl M, Beckmann MW, Lang U: Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol. 2007, 29: 407-413. 10.1002/uog.3930.CrossRefPubMed Schlembach D, Wallner W, Sengenberger R, Stiegler E, Mortl M, Beckmann MW, Lang U: Angiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol. 2007, 29: 407-413. 10.1002/uog.3930.CrossRefPubMed
Metadata
Title
Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study
Authors
Attila Molvarec
Nóra Gullai
Balázs Stenczer
Gergely Fügedi
Bálint Nagy
János Rigó Jr
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2013
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/1471-2393-13-161

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