[en] OBJECTIVE: Establish reference ranges for the Elecsys® soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) immunoassay ratio in twin pregnancies. METHODS: Data analyzed were from 3 prospective studies: Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia (PE) (PROGNOSIS), Study of Early-onset PE in Spain (STEPS), and a multicenter case-control study. Median, 5th, and 95th percentiles for sFlt-1, PlGF, and the sFlt-1/PlGF ratios were determined for normal twin pregnancies for 7 gestational windows and compared with the previous data for singleton pregnancies. RESULTS: The reference range analysis included 269 women with normal twin pregnancies. Before 29 weeks' gestation, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios did not differ between twin and singleton pregnancies. From 29 weeks' gestation to delivery, median, 5th, and 95th percentiles for sFlt-1/PlGF ratios were substantially higher in twin versus singleton pregnancies. sFlt-1 values were higher in women with twin pregnancies across all gestational windows. PlGF values were similar or higher in twin versus singleton pregnancies; PlGF concentrations increased from 10 weeks + 0 days to 28 weeks + 6 days' gestation. CONCLUSIONS: Reference ranges for the sFlt-1/PlGF ratio are similar in women with twin and singleton pregnancies until 29 weeks' gestation but appear higher in twin pregnancies thereafter.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
De La Calle, Maria; Division of Obstetrics and Maternal and Fetal Medicine, Hospital Universitario La
Delgado, Juan L; Department of Gynecology and Obstetrics, Universidad de Murcia and IMIB-Arrixaca,
Verlohren, Stefan; Department of Obstetrics, Charité - Universitätsmedizin, Berlin, Germany.
Escudero, Ana Isabel; Department of Obstetrics and Gynaecology, Hospital Universitario Central de
Bartha, Jose L; Division of Obstetrics and Maternal and Fetal Medicine, Hospital Universitario La
Campillos, Jose M; Department of Obstetrics, Hospital Universitario Miguel Servet, Zaragoza, Spain.
Aguarón De La Cruz, Angel; Department of Gynecology and Obstetrics, Hospital General Universitario Gregorio
Chantraine, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR) ; Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de
García Hernández, José Ángel; Department of Obstetrics and Gynecology, Hospital Universitario Materno Infantil
Herraiz, Ignacio; Department of Obstetrics and Gynaecology, Fetal Medicine Unit-SAMID, Hospital
Llurba, Elisa; Obstetrics and Gynaecology Department, High Risk Unit & Biomedical Research ; School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. ; Institute of Health Carlos III, Maternal and Child Health and Development Network
Kurka, Hedwig; Biostatistics and Data Management CPS, Roche Diagnostics GmbH, Penzberg, Germany.
Guo, Ge; Biostatistics and Data Management CPS, Roche Diagnostics Operations, Inc.,
Sillman, Johanna; Centralised and Point of Care Solutions, Roche Diagnostics International Ltd.,
Hund, Martin; Centralised and Point of Care Solutions, Roche Diagnostics International Ltd.,
Perales Marín, Alfredo; Department of Obstetrics and Gynecology, Hospital Universitario y Politécnico La
Rao A, Sairam S, Shehata H. Obstetric complications of twin pregnancies. Best Pract Res Clin Obstet Gynaecol. 2004; 18(4): 557-76.
Krotz S, Fajardo J, Ghandi S, Patel A, Keith LG. Hypertensive disease in twin pregnancies: a review. Twin Res. 2002; 5(1): 8-14.
Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7): 672-83.
Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. CPEP study group: soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006; 355: 992-1005.
Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, et al. 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-e11.
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, 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): 58-8.
Verlohren S, Herraiz I, Lapaire O, Schlembach D, Zeisler H, Calda P, 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(2): 346-52.
Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, 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): 649-58.
Faupel-Badger JM, McElrath TF, Lauria M, Houghton LC, Lim KH, Parry S, et al. Maternal circulating angiogenic factors in twin and singleton pregnancies. Am J Obstet Gynecol. 2015; 212(5): 636-8.
Dröge L, Herraìz I, Zeisler H, Schlembach D, Stepan H, Küssel L, et al. Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies. Ultrasound Obstet Gynecol. 2015; 45(3): 286-93.
Maynard SE, Moore Simas TA, Solitro MJ, Rajan A, Crawford S, Soderland P, et al. Circulating angiogenic factors in singleton vs multiple-gestation pregnancies. Am J Obstet Gynecol. 2008; 198(2): 200-7.
Maynard SE, Crawford SL, Bathgate S, Yan J, Robidoux L, Moore M, et al. Gestational angiogenic biomarker patterns in high risk preeclampsia groups. Am J Obstet Gynecol. 2013; 209(1): 53-9.
Rana S, Hacker MR, Modest AM, Salahuddin S, Lim KH, Verlohren S, et al. Circulating angiogenic factors and risk of adverse maternal and perinatal outcomes in twin pregnancies with suspected preeclampsia. Hypertension. 2012; 60(2): 451-8.
Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012; 125(7): 911-9.
Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennström M, et al. Predictive value of the sFlt-1: PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016; 374(1): 13-22.
Hund M, Allegranza D, Schoedl M, Dilba P, Verhagen-Kamerbeek W, Stepan H. Multicenter prospective clinical study to evaluate the prediction of short-term outcome in pregnant women with suspected preeclampsia (PROGNOSIS): study protocol. BMC Pregnancy Childbirth. 2014; 14: 324.
Bian X, Biswas A, Huang X, Lee KJ, Li TK, Masuyama H, et al. Short-term prediction of adverse outcomes using the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio in Asian women with suspected preeclampsia. Hypertension. 2019; 74(1): 164-72.
Cerdeira AS, O'Sullivan J, Ohuma EO, Harrington D, Szafranski P, Black R, et al. Randomized interventional study on prediction of preeclampsia/eclampsia in women with suspected preeclampsia: INSPIRE. Hypertension. 2019; 74(4): 983-90.
Bdolah Y, Lam C, Rajakumar A, Shivalingappa V, Mutter W, Sachs BP, et al. Twin pregnancy and the risk of preeclampsia: bigger placenta or relative ischemia? Am J Obstet Gynecol. 2008; 198(4): 428-6.
Cerdeira AS, Kandzija N, Pargmae P, Cooke W, James T, Redman C, et al. Circulating soluble fms-like tyrosine kinase-1 is placentally derived in normal pregnancy: First in vivo evidence. Pregnancy Hypertens. 2019; 16: 145-7.
Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypertens. 2017; 31(12): 782-6.
Hytten F. Blood volume changes in normal pregnancy. Clin Haematol. 1985; 14(3): 601-12.
Perales A, Delgado JL, De La Calle M, Garciá-Hernández JA, Escudero AI, Campillos JM, et al. STEPS investigators: sFlt-1/PlGF for earlyonset pre-eclampsia prediction: STEPS (study of early pre-eclampsia in Spain). Ultrasound Obstet Gynecol. 2016; 50: 373-82.
Breathnach FM, McAuliffe FM, Geary M, Daly S, Higgins JR, Dornan J, et al. Optimum timing for planned delivery of uncomplicated monochorionic and dichorionic twin pregnancies. Obstet Gynecol. 2012; 119(1): 50-9.
Cheong-See F, Schuit E, Arroyo-Manzano D, Khalil A, Barrett J, Joseph KS, et al. Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis. BMJ. 2016; 354: i4353.
National Institute of Health and Care Excellence (NICE): Twin and triplet pregnancy: NICE guideline [NG137]. Available at: https://www. nice. org. uk/guidance/ng137/chapter/Recommendations#timing-of-birth. Accessed 2020 Jun 26.
Stepan H, Hund M, Dilba P, Sillman J, Schlembach D. Elecsys® and Kryptor immunoassays for the measurement of sFlt-1 and PlGF to aid preeclampsia diagnosis: are they comparable? Clin Chem Lab Med. 2019; 57: 1339-48.
Lefèvre G, Hertig A, Guibourdenche J, Lévy P, Bailleul S, Drouin D, et al. Decision-making based on sFlt-1/PlGF ratios: are immunoassay results interchangeable for diagnosis or prognosis of preeclampsia? Clin Chem Lab Med. 2020.
Binder J, Palmrich P, Pateisky P, Kalafat E, Kuessel L, Zeisler H, et al. The prognostic value of angiogenic markers in twin pregnancies to predict delivery due to maternal complications of preeclampsia. Hypertension. 2020; 76(1): 176-83.
Saleh L, Tahitu SIM, Danser AHJ, van den Meiracker AH, Visser W. The predictive value of the sFlt-1/PlGF ratio on short-term absence of preeclampsia and maternal and fetal or neonatal complications in twin pregnancies. Pregnancy Hypertens. 2018; 14: 222-7.
