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Expert Reviews| Volume 223, ISSUE 1, P12-23.e7, July 2020

The competing risk approach for prediction of preeclampsia

Published:November 13, 2019DOI:https://doi.org/10.1016/j.ajog.2019.11.1247
      The established method of the assessment of the risk for development of preeclampsia is to identify risk factors from maternal demographic characteristics and medical history; in the presence of such factors, the patient is classified as high risk and in their absence as low risk. Although this approach is simple to perform, it has poor performance of the prediction of preeclampsia and does not provide patient-specific risks. This review describes a new approach that allows the estimation of patient-specific risks of delivery with preeclampsia before any specified gestational age by maternal demographic characteristics and medical history with biomarkers obtained either individually or in combination at any stage in pregnancy. In the competing risks approach, every woman has a personalized distribution of gestational age at delivery with preeclampsia; whether she experiences preeclampsia or not before a specified gestational age depends on competition between delivery before or after the development of preeclampsia. The personalized distribution comes from the application of Bayes theorem to combine a previous distribution, which is determined from maternal factors, with likelihoods from biomarkers. As new data become available, what were posterior probabilities take the role as the previous probability, and data collected at different stages are combined by repeating the application of Bayes theorem to form a new posterior at each stage, which allows for dynamic prediction of preeclampsia. The competing risk model can be used for precision medicine and risk stratification at different stages of pregnancy. In the first trimester, the model has been applied to identify a high-risk group that would benefit from preventative therapeutic interventions. In the second trimester, the model has been used to stratify the population into high-, intermediate-, and low-risk groups in need of different intensities of subsequent monitoring, thereby minimizing unexpected adverse perinatal events. The competing risks model can also be used in surveillance of women presenting to specialist clinics with signs or symptoms of hypertensive disorders; combination of maternal factors and biomarkers provide patient-specific risks for preeclampsia that lead to personalized stratification of the intensity of monitoring, with risks updated on each visit on the basis of biomarker measurements.

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      References

        • Rolnik D.L.
        • Wright D.
        • Poon L.C.
        • et al.
        Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.
        N Engl J Med. 2017; 377: 613-622
        • Roberge S.
        • Bujold E.
        • Nicolaides K.H.
        Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis.
        Am J Obstet Gynecol. 2018; 218: 287-293.e1
        • Koopmans C.M.
        • Bijlenga D.
        • Groen H.
        • et al.
        Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial.
        Lancet. 2009; 374: 979-988
        • National Collaborating Centre for Women’s and Children’s Health (UK)
        Hypertension in pregnancy: the management of hypertensive disorders during pregnancy.
        RCOG Press, London2010
        • ACOG Committee Opinion No
        743. Summary: low-dose aspirin use during pregnancy.
        Obstet Gynecol. 2018; 132: 254-256
        • Wright D.
        • Syngelaki A.
        • Akolekar R.
        • Poon L.C.
        • Nicolaides K.H.
        Competing risks model in screening for preeclampsia by maternal characteristics and medical history.
        Am J Obstet Gynecol. 2015; 213: 62.e1-62.e10
        • Tan M.Y.
        • Wright D.
        • Syngelaki A.
        • et al.
        Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE.
        Ultrasound Obstet Gynecol. 2018; 51: 743-750
        • Plasencia W.
        • Maiz N.
        • Bonino S.
        • Kaihura C.
        • Nicolaides K.H.
        Uterine artery Doppler at 11+0 to 13+6 weeks in the prediction of pre-eclampsia.
        Ultrasound Obstet Gynecol. 2007; 30: 742-749
        • Akolekar R.
        • Zaragoza E.
        • Poon L.C.
        • Pepes S.
        • Nicolaides K.H.
        Maternal serum placental growth factor at 11+0 to 13+6 weeks of gestation in the prediction of pre-eclampsia.
        Ultrasound Obstet Gynecol. 2008; 32: 732-739
        • Poon L.C.
        • Maiz N.
        • Valencia C.
        • Plasencia W.
        • Nicolaides K.H.
        First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia.
        Ultrasound Obstet Gynecol. 2009; 33: 23-33
        • Poon L.C.
        • Kametas N.A.
        • Chelemen T.
        • Leal A.
        • Nicolaides K.H.
        Maternal risk factors for hypertensive disorders in pregnancy: a multivariate approach.
        J Hum Hypertens. 2010; 24: 104-110
        • Poon L.C.
        • Akolekar R.
        • Lachmann R.
        • Beta J.
        • Nicolaides K.H.
        Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11-13 weeks.
        Ultrasound Obstet Gynecol. 2010; 35: 662-670
        • Akolekar R.
        • Syngelaki A.
        • Sarquis R.
        • Zvanca M.
        • Nicolaides K.H.
        Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks.
        Prenat Diagn. 2011; 31: 66-74
        • Scazzocchio E.
        • Figueras F.
        • Crispi F.
        • et al.
        Performance of a first-trimester screening of preeclampsia in a routine care low-risk setting.
        Am J Obstet Gynecol. 2013; 208: 203.e1-203.e10
        • Baschat A.A.
        • Magder L.S.
        • Doyle L.E.
        • Atlas R.O.
        • Jenkins C.B.
        • Blitzer M.G.
        Prediction of preeclampsia utilizing the first trimester screening examination.
        Am J Obstet Gynecol. 2014; 211: 514.e1-514.e7
        • Crovetto F.
        • Figueras F.
        • Triunfo S.
        • et al.
        First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors.
        Prenat Diagn. 2015; 35: 183-191
        • Wright D.
        • Akolekar R.
        • Syngelaki A.
        • Poon L.
        • Nicolaides K.H.
        A competing risks model in early screening for preeclampsia.
        Fetal Diagn Ther. 2012; 32: 171-178
        • Akolekar R.
        • Syngelaki A.
        • Poon L.
        • Wright D.
        • Nicolaides K.H.
        Competing risks model in early screening for preeclampsia by biophysical and biochemical markers.
        Fetal Diagn Ther. 2013; 33: 8-15
        • O’Gorman N.
        • Wright D.
        • Syngelaki A.
        • et al.
        Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation.
        Am J Obstet Gynecol. 2016; 214: 103.e1-103.e12
        • Royston P.
        • Thompson S.G.
        Model-based screening by risk with application to Down’s syndrome.
        Stat Med. 1992; 11: 257-268
        • Kalbfleisch J.D.
        • Prentice R.L.
        The statistical analysis of failure time data.
        Wiley & Sons; 2002, Hoboken, NJ2002
        • Francisco C.
        • Wright D.
        • Benkő Z.
        • Syngelaki A.
        • Nicolaides K.H.
        Hidden high rate of preeclampsia in twin compared to singleton pregnancies.
        Ultrasound Obstet Gynecol. 2017; 50: 88-92
        • Francisco C.
        • Wright D.
        • Benkő Z.
        • Syngelaki A.
        • Nicolaides K.H.
        Competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2017; 50: 501-506
        • Benkő Z.
        • Chaveeva P.
        • de Paco Matallana C.
        • et al.
        Validation of competing risks model in screening for pre-eclampsia in twin pregnancy by maternal factors.
        Ultrasound Obstet Gynecol. 2019; 53: 649-654
        • Benkő Z.
        • Chaveeva P.
        • de Paco Matallana C.
        • Zingler E.
        • Wright D.
        • Nicolaides K.H.
        Revised competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2019; 54: 617-624
        • O’Gorman N.
        • Tampakoudis G.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Uterine artery pulsatility index at 12, 22, 32 and 36 weeks’ gestation in screening for pre-eclampsia.
        Ultrasound Obstet Gynecol. 2016; 47: 565-572
        • Tayyar A.
        • Krithinakis K.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Mean arterial pressure at 12, 22, 32 and 36 weeks’ gestation in screening for pre-eclampsia.
        Ultrasound Obstet Gynecol. 2016; 47: 573-579
        • Tsiakkas A.
        • Cazacu R.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Maternal serum placental growth factor at 12, 22, 32 and 36 weeks’ gestation in screening for pre-eclampsia.
        Ultrasound Obstet Gynecol. 2016; 47: 472-477
        • Tsiakkas A.
        • Mendez O.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Maternal serum soluble fms-like tyrosine kinase-1 at 12, 22, 32 and 36 weeks’ gestation in screening for pre-eclampsia.
        Ultrasound Obstet Gynecol. 2016; 47: 478-483
        • Gallo D.M.
        • Wright D.
        • Casanova C.
        • Campanero M.
        • Nicolaides K.H.
        Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks’ gestation.
        Am J Obstet Gynecol. 2016; 214: 619.e1-619.e17
        • Tsiakkas A.
        • Saiid Y.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks’ gestation.
        Am J Obstet Gynecol. 2016; 215: 87.e1-87.e17
        • Andrietti S.
        • Silva M.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 35-37 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2016; 48: 72-79
        • Wald N.J.
        • Cuckle H.
        • Brock J.H.
        • Peto R.
        • Polani P.E.
        • Woodford F.P.
        Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy: report of UK collaborative study on alpha-fetoprotein in relation to neural-tube defects.
        Lancet. 1977; 1: 1323-1332
        • Tayyar A.
        • Guerra L.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Uterine artery pulsatility index in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 689-697
        • Wright A.
        • Wright D.
        • Ispas C.A.
        • Poon L.C.
        • Nicolaides K.H.
        Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 698-706
        • Tsiakkas A.
        • Duvdevani N.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Serum placental growth factor in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 591-598
        • Tsiakkas A.
        • Duvdevani N.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Serum soluble fms-like tyrosine kinase-1 in the three trimesters of pregnancy: effects of maternal characteristics and medical history.
        Ultrasound Obstet Gynecol. 2015; 45: 584-590
        • O’Gorman N.
        • Wright D.
        • Poon L.C.
        • et al.
        Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2017; 49: 751-755
        • Tan M.Y.
        • Syngelaki A.
        • Poon L.C.
        • et al.
        Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2018; 52: 186-195
        • Wright D.
        • Tan M.Y.
        • O’Gorman N.
        • et al.
        Predictive performance of the competing risk model in screening for preeclampsia.
        Am J Obstet Gynecol. 2019; 220: 199.e1-199.e13
        • Wright D.
        • Rolnik D.L.
        • Syngelaki A.
        • et al.
        Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit.
        Am J Obstet Gynecol. 2018; 218: 612.e1-612.e6
        • Wright D.
        • Gallo D.M.
        • Gil Pugliese S.
        • Casanova C.
        • Nicolaides K.H.
        Contingent screening for preterm pre-eclampsia.
        Ultrasound Obstet Gynecol. 2016; 47: 554-559
        • Wright A.
        • Wright D.
        • Syngelaki A.
        • Georgantis A.
        • Nicolaides K.H.
        Two-stage screening for preterm preeclampsia at 11-13 weeks’ gestation.
        Am J Obstet Gynecol. 2019; 220: 197.e1-197.e7
        • Litwinska M.
        • Wright D.
        • Efeturk T.
        • Ceccacci I.
        • Nicolaides K.H.
        Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 19-24 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2017; 50: 367-372
        • Litwinska M.
        • Syngelaki A.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Management of pregnancies after combined screening for pre-eclampsia at 19-24 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2018; 52: 365-372
        • Wright D.
        • Dragan I.
        • Syngelaki A.
        • Akolekar R.
        • Nicolaides K.H.
        Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 30-34 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2017; 49: 194-200
        • Panaitescu A.M.
        • Wright D.
        • Militelo A.
        • Akolekar R.
        • Nicolaides K.H.
        Proposed clinical management of pregnancies after combined screening for preeclampsia at 35-37 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2017; 50: 383-387
        • Panaitescu A.
        • Ciobanu A.
        • Syngelaki A.
        • Wright A.
        • Wright D.
        • Nicolaides K.H.
        Screening for preeclampsia at 35–37 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2018; 52: 501-506
        • Maynard S.E.
        • Min J.Y.
        • Merchan J.
        • et al.
        Excess placental soluble fms-like tyrosine kinase 1 (sFlt-11) may contribute to endothelial dysfunction, hypertension, and proteinuria in pre-eclampsia.
        J Clin Invest. 2003; 111: 649-658
        • Levine R.J.
        • Maynard S.E.
        • Qian C.
        • et al.
        Circulating angiogenic factors and the risk of pre-eclampsia.
        N Engl J Med. 2004; 350: 672-683
        • Chaiworapongsa T.
        • Romero R.
        • Savasan Z.A.
        • 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 pre-eclampsia.
        J Matern Fetal Neonatal Med. 2011; 24: 1187-1207
        • Benton S.J.
        • Hu Y.
        • Xie F.
        • et al.
        Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison between two commercial immunoassays.
        Am J Obstet Gynecol. 2011; 205: 469.e1-469.e8
        • Verlohren S.
        • Herraiz I.
        • Lapaire O.
        • et al.
        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.e1-58.e8
        • Chappell L.C.
        • Duckworth S.
        • Seed P.T.
        • et al.
        Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study.
        Circulation. 2013; 128: 2121-2131
        • Chaiworapongsa T.
        • Romero R.
        • Korzeniewski S.J.
        • 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.e1-287.e15
        • Lai J.
        • Garcia-Tizon Larroca S.
        • Peeva G.
        • Poon L.C.
        • Wright D.
        • Nicolaides K.H.
        Competing risks model in screening for preeclampsia by serum placental growth factor and soluble fms-like tyrosine kinase-1 at 30-33 weeks’ gestation.
        Fetal Diagn Ther. 2014; 35: 240-248
        • Zeisler H.
        • Llurba E.
        • Chantraine F.
        • et al.
        Predictive value of the sFlt-1:PlGF ratio in women with suspected pre-eclampsia.
        N Engl J Med. 2016; 374: 13-22
        • Stepan H.
        • Hund M.
        • Gencay M.
        • et al.
        A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome.
        Hypertens Pregnancy. 2016; 35: 295-305
        • Dragan I.
        • Wright D.
        • Fiolna M.
        • Leipold G.
        • Nicolaides K.H.
        Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio >38: comparison of performance at 31-34 vs 35-37 weeks’ gestation.
        Ultrasound Obstet Gynecol. 2017; 49: 209-212
        • Ciobanu A.
        • Wright A.
        • Panaitescu A.
        • Syngelaki A.
        • Wright D.
        • Nicolaides K.H.
        Prediction of imminent preeclampsia at 35-37 weeks gestation.
        Am J Obstet Gynecol. 2019; 220: 584.e1-584.e11

      Linked Article

      • How to calculate the risk of preeclampsia in women with a history of positive screening
        American Journal of Obstetrics & GynecologyVol. 223Issue 2
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          With the current demonstration of the benefits of aspirin initiated in early pregnancy to prevent the most severe and preterm forms of preeclampsia, there is a growing interest for the prediction of preterm preeclampsia in the first trimester of pregnancy.1 In the review by Wright et al,2 the authors reported that approximately 90% of women who will develop early preeclampsia could be identified using a competing risks approach in the first trimester of pregnancy, with a false-positive rate of 10%.
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