title: Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study.
abstract: OBJECTIVE
  To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia.
  
  
  METHODS
  Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation.
  
  
  METHODS
  Pre-eclampsia.
  
  
  RESULTS
  Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability.
  
  
  CONCLUSIONS
  Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia.
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Avenue Appia 20, Geneva 1201, Switzerland. Electronic address: widmerm@who.int.
authors.forename: Mariana
authors.initials: M
authors.lastname: Widmer
authors.affiliation: Centro Rosarino de Estudios Perinatales (CREP), Rosario, Argentina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cuesta
authors.affiliation: Barts and the London Medical School, London, UK.
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Khan
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MA, United States; National Institutes of Health/Department of Health and Human Services, Detroit, MI, United States.
authors.forename: Agustin
authors.initials: A
authors.lastname: Conde-Agudelo
authors.affiliation: Centro Rosarino de Estudios Perinatales (CREP), Rosario, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Carroli
authors.affiliation: Department of Obstetrics and Gynaecology, Government Medical College and Hospital, Nagpur, Maharashtra State, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Fusey
authors.affiliation: Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, MA, United States.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland.
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Pisake
authors.initials: P
authors.lastname: Lumbiganon
authors.affiliation: Aga Khan University Hospital, Department of Obstetrics and Gynaecology, Nairobi, Kenya.
authors.forename: Evan
authors.initials: E
authors.lastname: Sequeira
authors.affiliation: Instituto de Investigación Nutricional, Lima, Peru.
authors.forename: Nelly
authors.initials: N
authors.lastname: Zavaleta
authors.affiliation: Department of Obstetrics and Gynaecology, Maternal Fetal Medicine Unit, Brescia University, Italy; Department of Obstetrics and Gynecology, University of Parma, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Frusca
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Avenue Appia 20, Geneva 1201, Switzerland.
authors.forename: A Metin
authors.initials: AM
authors.lastname: Gülmezoglu
authors.affiliation: Obstetrics & Gynecology, University of Chicago Pritzker School of Medicine, Chicago, IL, United States.
authors.forename: Marshall D
authors.initials: MD
authors.lastname: Lindheimer
mesh_terms: D000328:Adult; D042501:Angiogenic Proteins / Q000097:blood*; D001118:Argentina; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003105:Colombia; D005260:Female; D006801:Humans; D007194:India; D007558:Italy; D007630:Kenya; D010568:Peru; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis* / Q000652:urine; D011237:Predictive Value of Tests; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood / Q000652:urine; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013557:Switzerland; D013785:Thailand; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014944:World Health Organization
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenic biomarkers; Pre-eclampsia; Screening