2,806
Views
51
CrossRef citations to date
0
Altmetric
Original Article

The use of angiogenic biomarkers in maternal blood to identify which SGA fetuses will require a preterm delivery and mothers who will develop pre-eclampsia

, , , , , , & show all
Pages 1214-1228 | Received 30 Mar 2015, Accepted 02 May 2015, Published online: 14 Aug 2015

References

  • Romero R, Jeanty P. The detection of fetal growth disorders. Sem Ultrasound CT MR 1984;5:130–43
  • Goldenberg RL, Cutter GR, Hoffman HJ, et al. Intrauterine growth retardation: standards for diagnosis. Am J Obstet Gynecol 1989;161:271–7
  • Figueras F, Gardosi J. Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol 2011;204:288–300
  • Figueras F, Gratacos E. Stage-based approach to the management of fetal growth restriction. Prenat Diagn 2014;34:655–9
  • Gardosi J. Intrauterine growth restriction: new standards for assessing adverse outcome. Best Pract Res Clin Obstet Gynaecol 2009;23:741–9
  • Baschat AA. Fetal growth restriction – from observation to intervention. J Perinat Med 2010;38:239–46
  • Kinzler WL, Vintzileos AM. Fetal growth restriction: a modern approach. Curr Opin Obstet Gynecol 2008;20:125–31
  • Mongelli M, Gardosi J. Fetal growth. Curr Opin Obstet Gynecol 2000;12:111–15
  • Miller J, Turan S, Baschat AA. Fetal growth restriction. Semin Perinatol 2008;32:274–280
  • Mandruzzato G, Antsaklis A, Botet F, et al. Intrauterine restriction (IUGR). J Perinat Med 2008;36:277–81
  • Caughey AB. How best to diagnose and treat the small-for-gestational-age fetus. Am J Obstet Gynecol 2013;209:397–9
  • Bamberg C, Kalache KD. Prenatal diagnosis of fetal growth restriction. Semin Fetal Neonatal Med 2004;9:387–94
  • Zhang J, Merialdi M, Platt LD, et al. Defining normal and abnormal fetal growth: promises and challenges. Am J Obstet Gynecol 2010;202:522–8
  • Bamfo JE, Odibo AO. Diagnosis and management of fetal growth restriction. J Pregnancy 2011;2011:640715
  • Mayer C, Joseph KS. Fetal growth: a review of terms, concepts and issues relevant to obstetrics. Ultrasound Obstet Gynecol 2013;41:136–45
  • Deter RL, Harrist RB, Hadlock FP, et al. The use of ultrasound in the assessment of normal fetal growth: a review. J Clin Ultrasound 1981;9:481–93
  • Deter RL, Harrist RB, Hadlock FP, et al. The use of ultrasound in the detection of intrauterine growth retardation: a review. J Clin Ultrasound 1982;10:9–16
  • Geirsson RT, Persson PH. Diagnosis of intrauterine growth retardation using ultrasound. Clin Obstet Gynaecol 1984;11:457–80
  • Wladimiroff JW, Bloemsma CA, Wallenburg HC. Ultrasonic assessment of fetal head and body sizes in relation to normal and retarded fetal growth. Am J Obstet Gynecol 1978;131:857–60
  • Wittmann BK, Robinson HP, Aitchison T, et al. The value of diagnostic ultrasound as a screening test for intrauterine growth retardation: comparison of nine parameters. Am J Obstet Gynecol 1979;134:30–5
  • Martinez DA, Barton JL. Estimation of fetal body and fetal head volumes: description of technique and nomograms for 18 to 41 weeks of gestation. Am J Obstet Gynecol 1980;137:78–84
  • Hadlock FP, Deter RL, Harrist RB, et al. A date-independent predictor of intrauterine growth retardation: femur length/abdominal circumference ratio. AJR Am J Roentgenol 1983;141:979–84
  • Jordaan HV. Estimation of fetal weight by ultrasound. J Clin Ultrasound 1983;11:59–66
  • Chervenak FA, Romero R, Berkowitz RL, et al. Use of sonographic estimated fetal weight in the prediction of intrauterine growth retardation. Am J Perinatol 1984;1:298–301
  • Divon MY, Chamberlain PF, Sipos L, et al. Identification of the small for gestational age fetus with the use of gestational age-independent indices of fetal growth. Am J Obstet Gynecol 1986;155:1197–201
  • Yagel S, Zacut D, Igelstein S, et al. In utero ponderal index as a prognostic factor in the evaluation of intrauterine growth retardation. Am J Obstet Gynecol 1987;157:415–19
  • Reece EA, Goldstein I, Pilu G, et al. Fetal cerebellar growth unaffected by intrauterine growth retardation: a new parameter for prenatal diagnosis. Am J Obstet Gynecol 1987;157:632–8
  • Berkowitz GS, Chitkara U, Rosenberg J, et al. Sonographic estimation of fetal weight and Doppler analysis of umbilical artery velocimetry in the prediction of intrauterine growth retardation: a prospective study. Am J Obstet Gynecol 1988;158:1149–53
  • Gaziano E, Knox GE, Wager GP, et al. The predictability of the small-for-gestational-age infant by real-time ultrasound-derived measurements combined with pulsed Doppler umbilical artery velocimetry. Am J Obstet Gynecol 1988;158:1431–9
  • Lee W, Barton S, Comstock CH, et al. Transverse cerebellar diameter: a useful predictor of gestational age for fetuses with asymmetric growth retardation. Am J Obstet Gynecol 1991;165:1044–50
  • Galan HL, Ferrazzi E, Hobbins JC. Intrauterine growth restriction (IUGR): biometric and Doppler assessment. Prenat Diagn 2002;22:331–7
  • Carberry AE, Gordon A, Bond DM, et al. Customised versus population-based growth charts as a screening tool for detecting small for gestational age infants in low-risk pregnant women. Cochrane Database Syst Rev 2011;(12):CD008549
  • Serena C, Marchetti G, Rambaldi MP, et al. Stillbirth and fetal growth restriction. J Matern Fetal Neonatal Med 2013;26:16–20
  • Beazley JM, Underhill RA. Fallacy of the fundal height. Br Med J 1970;4:404–6
  • Belizan JM, Villar J, Nardin JC, et al. Diagnosis of intrauterine growth retardation by a simple clinical method: measurement of uterine height. Am J Obstet Gynecol 1978;131:643–6
  • Rosenberg K, Grant JM, Tweedie I, et al. Measurement of fundal height as a screening test for fetal growth retardation. Br J Obstet Gynaecol 1982;89:447–50
  • Calvert JP, Crean EE, Newcombe RG, et al. Antenatal screening by measurement of symphysis-fundus height. Br Med J (Clin Res Ed) 1982;285:846–9
  • Rogers MS, Needham PG. Evaluation of fundal height measurement in antenatal care. Aust N Z J Obstet Gynaecol 1985;25:87–90
  • Persson B, Stangenberg M, Lunell NO, et al. Prediction of size of infants at birth by measurement of symphysis fundus height. Br J Obstet Gynaecol 1986;93:206–11
  • Hepburn M, Rosenberg K. An audit of the detection and management of small-for-gestational age babies. Br J Obstet Gynaecol 1986;93:212–16
  • Lockwood CJ, Weiner S. Assessment of fetal growth. Clin Perinatol 1986;13:3–35
  • Lindhard A, Nielsen PV, Mouritsen LA, et al. The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial. Br J Obstet Gynaecol 1990;97:675–80
  • Backe B, Nakling J. Effectiveness of antenatal care: a population based study. Br J Obstet Gynaecol 1993;100:727–32
  • Mongelli M, Gardosi J. Symphysis-fundus height and pregnancy characteristics in ultrasound-dated pregnancies. Obstet Gynecol 1999;94:591–4
  • Gardosi J, Francis A. Controlled trial of fundal height measurement plotted on customised antenatal growth charts. Br J Obstet Gynaecol 1999;106:309–17
  • Bais JM, Eskes M, Pel M, et al. Effectiveness of detection of intrauterine growth retardation by abdominal palpation as screening test in a low risk population: an observational study. Eur J Obstet Gynecol Reprod Biol 2004;116:164–9
  • Griffiths A, Pinto A, Margarit L. A survey of methods used to measure symphysis fundal height. J Obstet Gynaecol 2008;28:692–4
  • Morse K, Williams A, Gardosi J. Fetal growth screening by fundal height measurement. Best Pract Res Clin Obstet Gynaecol 2009;23:809–18
  • Sparks TN, Cheng YW, McLaughlin B, et al. Fundal height: a useful screening tool for fetal growth? J Matern Fetal Neonatal Med 2011;24:708–12
  • Deter RL, Harrist RB, Hadlock FP, et al. Longitudinal studies of fetal growth with the use of dynamic image ultrasonography. Am J Obstet Gynecol 1982;143:545–54
  • Jeanty P, Cantraine F, Romero R, et al. A longitudinal study of fetal weight growth. J Ultrasound Med 1984;3:321–8
  • Deter RL, Rossavik IK, Harrist RB, et al. Mathematic modeling of fetal growth: development of individual growth curve standards. Obstet Gynecol 1986;68:156–61
  • Deter RL, Harrist RB. Growth standards for anatomic measurements and growth rates derived from longitudinal studies of normal fetal growth. J Clin Ultrasound 1992;20:381–8
  • Mongelli M, Gardosi J. Longitudinal study of fetal growth in subgroups of a low-risk population. Ultrasound Obstet Gynecol 1995;6:340–4
  • Falkner F. Ultrasonography and fetal growth: key perinatal factors. J Perinatol 1995;15:114–18
  • Nasrat HA. Use of ultrasound longitudinal data in the diagnosis of abnormal fetal growth. J Matern Fetal Med 1997;6:209–14
  • Owen P, Khan KS. Fetal growth velocity in the prediction of intrauterine growth retardation in a low risk population. Br J Obstet Gynaecol 1998;105:536–40
  • Villar J, Altman DG, Purwar M, et al. The objectives, design and implementation of the INTERGROWTH-21st Project. BJOG 2013;120:9–26, v
  • Villar J, Cheikh Ismail L, Victora CG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet 2014;384:857–68
  • Papageorghiou AT, Ohuma EO, Altman DG, et al. International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. Lancet 2014;384:869–79
  • Eriksen PS, Secher NJ, Weis-Bentzon M. Normal growth of the fetal biparietal diameter and the abdominal diameter in a longitudinal study. An evaluation of the two parameters in predicting fetal weight. Acta Obstet Gynecol Scand 1985;64:65–70
  • Nazarian LN, Halpern EJ, Kurtz AB, et al. Normal interval fetal growth rates based on obstetrical ultrasonographic measurements. J Ultrasound Med 1995;14:829–36
  • Papageorghiou AT, Sarris I, Ioannou C, et al. Ultrasound methodology used to construct the fetal growth standards in the INTERGROWTH-21st Project. BJOG 2013;120:27–32, v
  • Deter RL, Harrist RB, Hadlock FP, et al. Longitudinal studies of fetal growth using volume parameters determined with ultrasound. J Clin Ultrasound 1984;12:313–24
  • Jeanty P, Romero R, Hobbins JC. Fetal limb volume: a new parameter to assess fetal growth and nutrition. J Ultrasound Med 1985;4:273–82
  • Lee W, Deter RL, McNie B, et al. Individualized growth assessment of fetal soft tissue using fractional thigh volume. Ultrasound Obstet Gynecol 2004;24:766–74
  • Lee W, Deter RL, McNie B, et al. The fetal arm: individualized growth assessment in normal pregnancies. J Ultrasound Med 2005;24:817–28
  • Lee W, Deter RL, Sameera S, et al. Individualized growth assessment of fetal thigh circumference using three-dimensional ultrasonography. Ultrasound Obstet Gynecol 2008;31:520–8
  • Deter RL, Lee W, Sangi-Haghpeykar H, et al. Personalized third-trimester fetal growth evaluation: comparisons of individualized growth assessment, percentile line and conditional probability methods. J Matern Fetal Neonatal Med 2014. [Epub ahead of print]. doi: 10.3109/14767058.2014.995083
  • Deter RL, Lee W, Sangi-Haghpeykar H, et al. A modified prenatal growth assessment score for the evaluation of fetal growth in the third trimester using single and composite biometric parameters. J Matern Fetal Neonatal Med 2015;28:745–54
  • Deter RL, Lee W, Sangi-Haghpeykar H, et al. Individualized fetal growth assessment: critical evaluation of key concepts in the specification of third trimester size trajectories. J Matern Fetal Neonatal Med 2014;27:543–51
  • Ananth CV, Vintzileos AM. Distinguishing pathological from constitutional small for gestational age births in population-based studies. Early Hum Dev 2009;85:653–8
  • Xu H, Simonet F, Luo ZC. Optimal birth weight percentile cut-offs in defining small- or large-for-gestational-age. Acta Paediatr 2010;99:550–5
  • Galan HL. Timing delivery of the growth-restricted fetus. Semin Perinatol 2011;35:262–9
  • von Beckerath AK, Kollmann M, Rotky-Fast C, et al. Perinatal complications and long-term neurodevelopmental outcome of infants with intrauterine growth restriction. Am J Obstet Gynecol 2013;208:130.e131–6
  • Boers KE, Vijgen SM, Bijlenga D, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010;341:c7087
  • GRIT Study Group. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG 2003;110:27–32
  • Thornton JG, Hornbuckle J, Vail A, et al. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet 2004;364:513–20
  • Grimes DA. When to deliver the stunted fetus? Lancet 2004;364:483–4
  • Gardosi J. GRIT: concern about external validity. Lancet 2005;365:384; author reply 385
  • Walker DM, Marlow N, Upstone L, et al. The Growth Restriction Intervention Trial: long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet Gynecol 2011;204:34.e31–9
  • Trudell AS, Cahill AG, Tuuli MG, et al. Risk of stillbirth after 37 weeks in pregnancies complicated by small-for-gestational-age fetuses. Am J Obstet Gynecol 2013;208:376.e371–7
  • Trudell AS, Tuuli MG, Cahill AG, et al. Balancing the risks of stillbirth and neonatal death in the early preterm small-for-gestational-age fetus. Am J Obstet Gynecol 2014;211:295.e291–7
  • Eskenazi B, Fenster L, Sidney S, et al. Fetal growth retardation in infants of multiparous and nulliparous women with preeclampsia. Am J Obstet Gynecol 1993;169:1112–18
  • Churchill D, Perry IJ, Beevers DG. Ambulatory blood pressure in pregnancy and fetal growth. Lancet 1997;349:7–10
  • McCowan LM, North RA, Harding JE. Abnormal uterine artery Doppler in small-for-gestational-age pregnancies is associated with later hypertension. Aust N Z J Obstet Gynaecol 2001;41:56–60
  • Mitani M, Matsuda Y, Makino Y, et al. Clinical features of fetal growth restriction complicated later by preeclampsia. J Obstet Gynaecol Res 2009;35:882–7
  • Gilbert WM, Danielsen B. Pregnancy outcomes associated with intrauterine growth restriction. Am J Obstet Gynecol 2003;188:1596–9; discussion 1599–601
  • Kamoji VM, Dorling JS, Manktelow BN, et al. Extremely growth-retarded infants: is there a viability centile? Pediatrics 2006;118:758–63
  • Slattery MM, Geary M, Morrison JJ. Obstetric antecedents for preterm delivery. J Perinat Med 2008;36:306–9
  • Carreno CA, Costantine MM, Holland MG, et al. Approximately one-third of medically indicated late preterm births are complicated by fetal growth restriction. Am J Obstet Gynecol 2011;204:263.e261–4
  • Kramer MS, Olivier M, McLean FH, et al. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990;86:707–13
  • Simchen MJ, Beiner ME, Strauss-Liviathan N, et al. Neonatal outcome in growth-restricted versus appropriately grown preterm infants. Am J Perinatol 2000;17:187–92
  • Resnik R. Intrauterine growth restriction. Obstet Gynecol 2002;99:490–6
  • Ego A, Subtil D, Grange G, et al. Customized versus population-based birth weight standards for identifying growth restricted infants: a French multicenter study. Am J Obstet Gynecol 2006;194:1042–9
  • Getahun D, Ananth CV, Kinzler WL. Risk factors for antepartum and intrapartum stillbirth: a population-based study. Am J Obstet Gynecol 2007;196:499–507
  • Giapros V, Drougia A, Krallis N, et al. Morbidity and mortality patterns in small-for-gestational age infants born preterm. J Matern Fetal Neonatal Med 2012;25:153–7
  • Qiu X, Lodha A, Shah PS, et al. Neonatal outcomes of small for gestational age preterm infants in Canada. Am J Perinatol 2012;29:87–94
  • Pilliod RA, Cheng YW, Snowden JM, et al. The risk of intrauterine fetal death in the small-for-gestational-age fetus. Am J Obstet Gynecol 2012;207:318.e311–16
  • Voskamp BJ, Kazemier BM, Ravelli AC, et al. Recurrence of small-for-gestational-age pregnancy: analysis of first and subsequent singleton pregnancies in The Netherlands. Am J Obstet Gynecol 2013;208:374.e371–6
  • Katz J, Lee AC, Kozuki N, et al. Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet 2013;382:417–25
  • Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 2008;21:9–23
  • Boutsikou T, Malamitsi-Puchner A, Economou E, et al. Soluble vascular endothelial growth factor receptor-1 in intrauterine growth restricted fetuses and neonates. Early Hum Dev 2006;82:235–9
  • Crispi F, Dominguez C, Llurba E, et al. Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction. Am J Obstet Gynecol 2006;195:201–7
  • Savvidou MD, Yu CK, Harland LC, et al. Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction. Am J Obstet Gynecol 2006;195:1668–73
  • Schlembach D, Wallner W, Sengenberger R, et al. 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;29:407–13
  • Wallner W, Sengenberger R, Strick R, et al. Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction. Clin Sci (Lond) 2007;112:51–7
  • Chaiworapongsa T, Espinoza J, Gotsch F, et al. The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation. J Matern Fetal Neonatal Med 2008;21:25–40
  • Chaiworapongsa T, Romero R, Gotsch F, et al. Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age. J Matern Fetal Neonatal Med 2008;21:41–52
  • Erez O, Romero R, Espinoza J, et al. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern Fetal Neonatal Med 2008;21:279–87
  • Crispi F, Llurba E, Dominguez C, et al. Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;31:303–9
  • Asvold BO, Vatten LJ, Romundstad PR, et al. Angiogenic factors in maternal circulation and the risk of severe fetal growth restriction. Am J Epidemiol 2011;173:630–9
  • Sibiude J, Guibourdenche J, Dionne MD, et al. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One 2012;7:e50208
  • Benton SJ, Hu Y, Xie F, et al. Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction? Am J Obstet Gynecol 2012;206:163.e161–7
  • Lobmaier SM, Figueras F, Mercade I, et al. Angiogenic factors versus Doppler follow up in the prediction of adverse outcome among late pregnancy small-for-gestational-age fetuses. Ultrasound Obstet Gynecol 2014;43:533–40
  • Alahakoon TI, Zhang W, Trudinger BJ, et al. Discordant clinical presentations of preeclampsia and intrauterine fetal growth restriction with similar pro- and anti-angiogenic profiles. J Matern Fetal Neonatal Med 2014;27:1854–9
  • Lobmaier SM, Figueras F, Mercade I, et al. Angiogenic factors vs Doppler surveillance in the prediction of adverse outcome among late-pregnancy small-for- gestational-age fetuses. Ultrasound Obstet Gynecol 2014;43:533–40
  • Darling AM, McDonald CR, Conroy AL, et al. Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania. Am J Obstet Gynecol 2014;211:509.e501–8
  • Torry DS, Wang HS, Wang TH, et al. Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol 1998;179:1539–44
  • Reuvekamp A, Velsing-Aarts FV, Poulina IE, et al. Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia. Br J Obstet Gynaecol 1999;106:1019–22
  • Tidwell SC, Ho HN, Chiu WH, et al. Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia. Am J Obstet Gynecol 2001;184:1267–72
  • Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003;111:649–58
  • Taylor RN, Grimwood J, Taylor RS, et al. Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol 2003;188:177–82
  • Tsatsaris V, Goffin F, Munaut C, et al. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab 2003;88:5555–63
  • Luttun A, Carmeliet P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered? J Clin Invest 2003;111:600–2
  • Koga K, Osuga Y, Yoshino O, et al. Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J Clin Endocrinol Metab 2003;88:2348–51
  • Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672–83
  • Chaiworapongsa T, Romero R, Espinoza J, et al. Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia. Young Investigator Award. Am J Obstet Gynecol 2004;190:1541–7; discussion 1547–50
  • Chaiworapongsa T, Romero R, Kim YM, et al. Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia. J Matern Fetal Neonatal Med 2005;17:3–18
  • Park CW, Park JS, Shim SS, et al. An elevated maternal plasma, but not amniotic fluid, soluble fms-like tyrosine kinase-1 (sFlt-1) at the time of mid-trimester genetic amniocentesis is a risk factor for preeclampsia. Am J Obstet Gynecol 2005;193:984–9
  • Bujold E, Romero R, Chaiworapongsa T, et al. Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin. J Matern Fetal Neonatal Med 2005;18:9–16
  • Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 2006;355:992–1005
  • Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006;12:642–9
  • Unal ER, Robinson CJ, Johnson DD, et al. Second-trimester angiogenic factors as biomarkers for future-onset preeclampsia. Am J Obstet Gynecol 2007;197:211.e211–14
  • Widmer M, Villar J, Benigni A, et al. Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review. Obstet Gynecol 2007;109:168–80
  • Moore Simas TA, Crawford SL, Solitro MJ, et al. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol 2007;197:244.e241–8
  • Kusanovic JP, Romero R, Chaiworapongsa T, et al. 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;22:1021–38
  • Chaiworapongsa T, Romero R, Tarca AL, et al. A decrease in maternal plasma concentrations of sVEGFR-2 precedes the clinical diagnosis of preeclampsia. Am J Obstet Gynecol 2010;202:550.e1–10
  • Soto E, Romero R, Kusanovic JP, et al. 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. J Matern Fetal Neonatal Med 2012;25:498–507
  • Molvarec A, Szarka A, Walentin S, et al. Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia. Hypertens Res 2010;33:892–8
  • Chaiworapongsa T, Romero R, Savasan ZA, et al. 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. J Matern Fetal Neonatal Med 2011;24:1187–207
  • Rana S, Hacker MR, Modest AM, et al. Circulating angiogenic factors and risk of adverse maternal and perinatal outcomes in twin pregnancies with suspected preeclampsia. Hypertension 2012;60:451–8
  • Garovic VD. The role of angiogenic factors in the prediction and diagnosis of preeclampsia superimposed on chronic hypertension. Hypertension 2012;59:555–7
  • Ghosh SK, Raheja S, Tuli A, et al. Serum PLGF as a potential biomarker for predicting the onset of preeclampsia. Arch Gynecol Obstet 2012;285:417–22
  • Hagmann H, Thadhani R, Benzing T, et al. The promise of angiogenic markers for the early diagnosis and prediction of preeclampsia. Clin Chem 2012;58:837–45
  • Verlohren S, Stepan H, Dechend R. Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia. Clin Sci (Lond) 2012;122:43–52
  • Rana S, Cerdeira AS, Wenger J, et al. Plasma concentrations of soluble endoglin versus standard evaluation in patients with suspected preeclampsia. PLoS One 2012;7:e48259
  • Vatten LJ, Asvold BO, Eskild A. Angiogenic factors in maternal circulation and preeclampsia with or without fetal growth restriction. Acta Obstet Gynecol Scand 2012;91:1388–94
  • McElrath TF, Lim KH, Pare E, et al. Longitudinal evaluation of predictive value for preeclampsia of circulating angiogenic factors through pregnancy. Am J Obstet Gynecol 2012;207:407.e401–7
  • Rana S, Powe CE, Salahuddin S, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation 2012;125:911–19
  • Moore AG, Young H, Keller JM, et al. Angiogenic biomarkers for prediction of maternal and neonatal complications in suspected preeclampsia. J Matern Fetal Neonatal Med 2012;25:2651–7
  • Chaiworapongsa T, Romero R, Korzeniewski SJ, et al. 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 2014;27:132–44
  • Chaiworapongsa T, Romero R, Korzeniewski SJ, et al. Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia. Am J Obstet Gynecol 2013;208:287.e1–15
  • Chappell LC, Duckworth S, Seed PT, et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation 2013;128:2121–31
  • Verlohren S, Herraiz I, Lapaire O, et al. New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension 2014;63:346–52
  • Goel A, Rana S. Angiogenic factors in preeclampsia: potential for diagnosis and treatment. Curr Opin Nephrol Hypertens 2013;22:643–50
  • Moore Simas TA, Crawford SL, Bathgate S, et al. Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women. J Matern Fetal Neonatal Med 2014;27:1038–48
  • Rizos D, Eleftheriades M, Karampas G, et al. Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study. Eur J Obstet Gynecol Reprod Biol 2013;171:225–30
  • Schaarschmidt W, Rana S, Stepan H. The course of angiogenic factors in early- vs. late-onset preeclampsia and HELLP syndrome. J Perinat Med 2013;41:511–16
  • Maynard SE, Crawford SL, Bathgate S, et al. Gestational angiogenic biomarker patterns in high risk preeclampsia groups. Am J Obstet Gynecol 2013;209:53.e1–9
  • Reimer T, Rohrmann H, Stubert J, et al. Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: a matched-pair analysis. J Matern Fetal Neonatal Med 2013;26:263–9
  • Chaiworapongsa T, Chaemsaithong P, Yeo L, et al. Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 2014;10:466–80
  • Chaiworapongsa T, Chaemsaithong P, Korzeniewski SJ, et al. Pre-eclampsia part 2: prediction, prevention and management. Nat Rev Nephrol 2014;10:531–40
  • Moore Simas TA, Crawford SL, Bathgate S, et al. Angiogenic biomarkers for prediction of early preeclampsia onset in high-risk women. J Matern Fetal Neonatal Med 2014;27:1038–48
  • Romero R, Chaiworapongsa T, Erez O, et al. An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study. J Matern Fetal Neonatal Med 2010;23:1384–99
  • Espinoza J, Chaiworapongsa T, Romero R, et al. Unexplained fetal death: another anti-angiogenic state. J Matern Fetal Neonatal Med 2007;20:495–507
  • Smith GC, Crossley JA, Aitken DA, et al. Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth. Obstet Gynecol 2007;109:1316–24
  • Chaiworapongsa T, Kusanovic JP, Savasan ZA, et al. Fetal death: a condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments. J Matern Fetal Neonatal Med 2010;23:960–72
  • Daponte A, Pournaras S, Polyzos NP, et al. Soluble FMS-like tyrosine kinase-1 (sFlt-1) and serum placental growth factor (PlGF) as biomarkers for ectopic pregnancy and missed abortion. J Clin Endocrinol Metab 2011;96:E1444–51
  • Ferrazzi E, Vegni C, Bellotti M, et al. Role of umbilical Doppler velocimetry in the biophysical assessment of the growth-retarded fetus. Answers from neonatal morbidity and mortality. J Ultrasound Med 1991;10:309–15
  • Romero R, Kalache KD, Kadar N. Timing the delivery of the preterm severely growth-restricted fetus: venous Doppler, cardiotocography or the biophysical profile? Ultrasound Obstet Gynecol 2002;19:118–21
  • Ferrazzi E, Bozzo M, Rigano S, et al. Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus. Ultrasound Obstet Gynecol 2002;19:140–6
  • Soregaroli M, Bonera R, Danti L, et al. Prognostic role of umbilical artery Doppler velocimetry in growth-restricted fetuses. J Matern Fetal Neonatal Med 2002;11:199–203
  • Baschat AA, Gembruch U, Weiner CP, et al. Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses. Ultrasound Obstet Gynecol 2003;22:240–5
  • Berkley E, Chauhan SP, Abuhamad A. Doppler assessment of the fetus with intrauterine growth restriction. Am J Obstet Gynecol 2012;206:300–8
  • Unterscheider J, Daly S, Geary MP, et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol 2013;208:290.e291–6
  • Unterscheider J, Daly S, Geary MP, et al. Predictable progressive Doppler deterioration in IUGR: does it really exist? Am J Obstet Gynecol 2013;209:539.e531–7
  • Macones GA, Cahill A, Odibo A. Doppler deterioration in intrauterine growth restriction: Unterscheider et al. Am J Obstet Gynecol 2013;209:589
  • Ferrazzi E. The PORTO study and the gestational age perspective of Doppler interrogation of IUGR fetuses. Am J Obstet Gynecol 2014;211:314–15
  • Flood K, Unterscheider J, Daly S, et al. The role of brain sparing in the prediction of adverse outcomes in intrauterine growth restriction: results of the multicenter PORTO Study. Am J Obstet Gynecol 2014;211:288.e281–5
  • O'Dwyer V, Burke G, Unterscheider J, et al. Defining the residual risk of adverse perinatal outcome in growth-restricted fetuses with normal umbilical artery blood flow. Am J Obstet Gynecol 2014;211:420.e421–5
  • Savchev S, Figueras F, Gratacos E. Survey on the current trends in managing intrauterine growth restriction. Fetal Diagn Ther 2014;36:129–35
  • Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: systematic review with meta-analysis. Am J Obstet Gynecol 1995;172:1379–87
  • Morris RK, Malin G, Robson SC, et al. Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high-risk population: systematic review and bivariate meta-analysis. Ultrasound Obstet Gynecol 2011;37:135–42
  • Imdad A, Yakoob MY, Siddiqui S, et al. Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths. BMC Public Health 2011;11:S1
  • Vergani P, Roncaglia N, Andreotti C, et al. Prognostic value of uterine artery Doppler velocimetry in growth-restricted fetuses delivered near term. Am J Obstet Gynecol 2002;187:932–6
  • Severi FM, Bocchi C, Visentin A, et al. Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002;19:225–8
  • Ghosh GS, Gudmundsson S. Uterine and umbilical artery Doppler are comparable in predicting perinatal outcome of growth-restricted fetuses. BJOG 2009;116:424–30
  • Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129–33
  • Alexander GR, Himes JH, Kaufman RB, et al. A United States national reference for fetal growth. Obstet Gynecol 1996;87:163–8
  • ACOG Practice Bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 2002;99:159–67
  • Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–22
  • Chaiworapongsa T, Romero R, Kusanovic JP, et al. Plasma soluble endoglin concentration in pre-eclampsia is associated with an increased impedance to flow in the maternal and fetal circulations. Ultrasound Obstet Gynecol 2010;35:155–62
  • Trudinger BJ, Cook CM, Giles WB, et al. Fetal umbilical artery velocity waveforms and subsequent neonatal outcome. Br J Obstet Gynaecol 1991;98:378–84
  • Chen WJ, Samuelson FW, Gallas BD, et al. On the assessment of the added value of new predictive biomarkers. BMC Med Res Methodol 2013;13:98
  • Demler OV, Pencina MJ, D'Agostino RB. Misuse of DeLong test to compare AUCs for nested models. Stat Med 2012;31:2577–87
  • Pepe MS, Kerr KF, Longton G, et al. Testing for improvement in prediction model performance. Stat Med 2013;32:1467–82
  • Nicolaides KH, Bilardo CM, Soothill PW, et al. Absence of end diastolic frequencies in umbilical artery: a sign of fetal hypoxia and acidosis. BMJ 1988;297:1026–7
  • Yoon BH, Oh IH, Lee PR, et al. Is an abnormal Doppler umbilical artery waveform ratio a risk factor for poor perinatal outcome in the non-small for gestational age fetus? Am J Perinatol 1993;10:245–9
  • Giles W, Bisits A. Clinical use of Doppler ultrasound in pregnancy: information from six randomised trials. Fetal Diagn Ther 1993;8:247–55
  • DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45
  • Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation 2007;115:928–35
  • Vickers A, Cronin A, Begg C. One statistical test is sufficient for assessing new predictive markers. BMC Med Res Methodol 2011;11:13

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.