Screening models using multiple markers for early detection of late-onset preeclampsia in low-risk pregnancy

BMC Pregnancy and Childbirth

Dong Hyun Cha¹  Kyoung Jin Lee²  Margherita Zanello³  Antonio Farina³  Yeon Kyung Cho²  Ji Yeon Kim²  Sung Shin Shim²  Yong Wook Jung²  Soo Hyun Kim²  Hee Jin Park² 

[1] Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, 650-9 Yeoksam-dong, Gangnam-gu, Seoul, Republic of Korea;Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea;Department of Medicine and Surgery (DIMEC), Division of Prenatal Medicine, University of Bologna, Bologna, Italy

关键词: Low-risk population;    BMI;    PAPP-A;    sFlt-1/PlGF ratio;    PlGF;    sFlt-1;    Placental growth factor;    Soluble fms-like tyrosine kinase;    Preeclampsia;   

Others  :  1131727
DOI  :  10.1186/1471-2393-14-35

 received in 2013-09-28, accepted in 2014-01-14,  发布年份 2014

【 摘 要 】

Background

Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down’s syndrome screening, to predict preeclampsia.

Methods

This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation.

Results

Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%.

Conclusions

The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker.

【 授权许可】

   
2014 Park et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]World Health Organization, et al.: World Health Report 2005: make every mother and child count. Geneva: chapter three- great expectations: making pregnancy safer; 2005:41-58.
• [2]Phillips JK, Janowiak M, Badger GJ, Bernstein IM: Evidence for distinct preterm and term phenotypes of preeclampsia. J Matern Fetal Neonatal Med 2010, 23(7):622-626.
• [3]Raymond D, Peterson E: A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 2011, 66(8):497-506.
• [4]Costa Fda S, Murthi P, Keogh R, Woodrow N: Early screening for preeclampsia. Rev Bras Ginecol Obstet 2011, 33(11):367-375.
• [5]Roberts JM, Pearson GD, Cutler JA, Lindheimer MD: Summary of the NHLBI Working Group on Research on Hypertension during Pregnancy. Hypertens Pregnancy 2003, 22(2):109-127.
• [6]Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, VanDorsten P, Landon M, Paul R, Miodovnik M, et al.: Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 1998, 338(11):701-705.
• [7]Herraiz I, Escribano D, Gomez-Arriaga PI, Hernindez-Garcia JM, Herraiz MA, Galindo A: Predictive value of sequential models of uterine artery Doppler in pregnancies at high risk for pre-eclampsia. Ultrasound Obstet Gynecol 2012, 40(1):68-74.
• [8]Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, 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(5):649-658.
• [9]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(2):161.e1-161.e11.
• [10]Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A, Engels T, 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(1):58. e51–58
• [11]Poon LC, Akolekar R, Lachmann R, Beta J, Nicolaides KH: Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11–13 weeks. Ultrasound Obstet Gynecol 2010, 35(6):662-670.
• [12]Yu CK, Smith GC, Papageorghiou AT, Cacho AM, Nicolaides KH: An integrated model for the prediction of preeclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women. Am J Obstet Gynecol 2005, 193(2):429-436.
• [13]Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM: Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab 2002, 87(4):1762-1767.
• [14]Muttukrishna S, North RA, Morris J, Schellenberg JC, Taylor RS, Asselin J, Ledger W, Groome N, Redman CW: Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia. Hum Reprod 2000, 15(7):1640-1645.
• [15]Sibai BM, Koch MA, Freire S, Silva JL P e, Rudge MV, Martins-Costa S, Bartz J, de Barros Santos C, Cecatti JG, Costa R, et al.: Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia? Am J Obstet Gynecol 2008, 199(3):268. e261–269
• [16]Aquilina J, Maplethorpe R, Ellis P, Harrington K: Correlation between second trimester maternal serum inhibin-A and human chorionic gonadotrophin for the prediction of pre-eclampsia. Placenta 2000, 21(5–6):487-492.
• [17]Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy Am J Obstet Gynecol 2000, 183(1):S1-S22.
• [18]Sibai BM: Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 2003, 102(1):181-192.
• [19]Obed S, Patience A: Birth weight and ponderal index in pre-eclampsia: a comparative study. Ghana Med J 2006, 40(1):8-13.
• [20]Ihle BU, Long P, Oats J: Early onset pre-eclampsia: recognition of underlying renal disease. BMJ 1987, 294(6564):79-81.
• [21]Crispi F, Llurba E, Dominguez C, Martin-Gallan P, Cabero L, Gratacos E: 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(3):303-309.
• [22]Dissanayake VH, Samarasinghe HD, Morgan L, Jayasekara RW, Seneviratne HR, Broughton Pipkin F: Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka. J Obstet Gynaecol Res 2007, 33(1):56-62.
• [23]Wolf M, Sandler L, Munoz K, Hsu K, Ecker JL, Thadhani R: First trimester insulin resistance and subsequent preeclampsia: a prospective study. J Clin Endocrinol Metab 2002, 87(4):1563-1568.
• [24]Marshall NE, Guild C, Cheng YW, Caughey AB, Halloran DR: Maternal superobesity and perinatal outcomes. Am J Obstet Gynecol 2012, 206(5):417. e411–416
• [25]Lee CJ, Hsieh TT, Chiu TH, Chen KC, Lo LM, Hung TH: Risk factors for pre-eclampsia in an Asian population. Int J Gynaecol Obstet 2000, 70(3):327-333.
• [26]Duckitt K, Harrington D: Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005, 330(7491):565.
• [27]Rurangirwa AA, Gaillard R, Steegers EA, Hofman A, Jaddoe VW: Hemodynamic adaptations in different trimesters among nulliparous and multiparous pregnant women; the Generation R study. Am J Hypertens 2012, 25(8):892-899.
• [28]Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, Yates JR 3rd, Conover CA: The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci USA 1999, 96(6):3149-3153.
• [29]Petraglia F, Vaughan J, Vale W: Inhibin and activin modulate the release of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone from cultured human placental cells. Proc Natl Acad Sci USA 1989, 86(13):5114-5117.
• [30]Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH: Multicenter screening for pre-eclampsia and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of gestation. Ultrasound Obstet Gynecol 2001, 18(5):441-449.
• [31]Cnossen JS, Morris RK, ter Riet G, Mol BW, van der Post JA, Coomarasamy A, Zwinderman AH, Robson SC, Bindels PJ, Kleijnen J, et al.: Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis. CMAJ 2008, 178(6):701-711.
• [32]Roberts JM, Cooper DW: Pathogenesis and genetics of pre-eclampsia. Lancet 2001, 357(9249):53-56.
• [33]Parra M, Rodrigo R, Barja P, Bosco C, Fernandez V, Munoz H, Soto-Chacon E: Screening test for preeclampsia through assessment of uteroplacental blood flow and biochemical markers of oxidative stress and endothelial dysfunction. Am J Obstet Gynecol 2005, 193(4):1486-1491.
• [34]da Silva CF, da Cunha SP, Berezowsky AT: Dopplervelocimetria das artérias uterinas na predição de complicações em gestações de baixo risco. Rev Bras Ginecol Obstet 2005, 27(6):323-330.
• [35]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(5):422-427.
• [36]Soto E, Romero R, Kusanovic JP, Ogge G, Hussein Y, Yeo L, Hassan SS, Kim CJ, Chaiworapongsa T: 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(5):498-507.
• [37]Arduini D, Rizzo G: Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 1990, 18(3):165-172.
• [38]Poon LC, Syngelaki A, Akolekar R, Lai J, Nicolaides KH: Combined screening for preeclampsia and small for gestational age at 11–13 weeks. Fetal Diagn Ther 2013, 33(1):16-27.
• [39]Saxena AR, Seely EW, Rich-Edwards JW, Wilkins-Haug LE, Karumanchi SA, McElrath TF: First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia. BMC Pregnancy Childbirth 2013, 13:85. BioMed Central Full Text
• [40]Poon LC, Kametas NA, Valencia C, Chelemen T, Nicolaides KH: Hypertensive disorders in pregnancy: screening by systolic diastolic and mean arterial pressure at 11–13 weeks. Hypertens Pregnancy 2011, 30(1):93-107.
• [41]Schoofs K, Grittner U, Engels T, Pape J, Denk B, Henrich W, Verlohren S: The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction. J Perinat Med 2014, 42(1):61-68.