Mariana Widmer1, Cristina Cuesta2, Khalid S Khan3, Agustin Conde-Agudelo4, Guillermo Carroli2, Shalini Fusey5, S Ananth Karumanchi6, Olav Lapaire7, Pisake Lumbiganon8, Evan Sequeira9, Nelly Zavaleta10, Tiziana Frusca11, A Metin Gülmezoglu12, Marshall D Lindheimer13. 1. 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. 2. Centro Rosarino de Estudios Perinatales (CREP), Rosario, Argentina. 3. Barts and the London Medical School, London, UK. 4. 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. 5. Department of Obstetrics and Gynaecology, Government Medical College and Hospital, Nagpur, Maharashtra State, India. 6. Beth Israel Deaconess Medical Centre and Harvard Medical School, Boston, MA, United States. 7. Department of Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland. 8. Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 9. Aga Khan University Hospital, Department of Obstetrics and Gynaecology, Nairobi, Kenya. 10. Instituto de Investigación Nutricional, Lima, Peru. 11. Department of Obstetrics and Gynaecology, Maternal Fetal Medicine Unit, Brescia University, Italy; Department of Obstetrics and Gynecology, University of Parma, Italy. 12. 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. 13. Obstetrics & Gynecology, University of Chicago Pritzker School of Medicine, Chicago, IL, United States.
Abstract
OBJECTIVE: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. DESIGN: 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. MAIN OUTCOME MEASURE: 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.
OBJECTIVE: To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. DESIGN: 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. MAIN OUTCOME MEASURE: 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.
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