First trimester urinary placental growth factor and development of pre-eclampsia MD Savvidou, a R Akolekar, b E Zaragoza, b LC Poon, b KH Nicolaides b a Department of Obstetrics, Chelsea and Westminster Hospital, London, UK b Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK Correspondence: Dr MD Savvidou, Department of Obstetrics, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. Email msavvidou@dsla.ndo.co.uk Accepted 11 November 2008. Published Online 11 February 2009. Objective To compare urinary placental growth factor (PlGF) concentration at 11 +0 to 13 +6 weeks of gestation in women who subsequently develop pre-eclampsia with normotensive controls. Design Nested case–control study within a prospective study for first trimester prediction of pre-eclampsia. Setting Routine antenatal visit in a teaching hospital. Population Fifty-two women who developed pre-eclampsia and 52 controls matched for gestational age and sample storage time. Methods Urinary PlGF concentration and PlGF to creatinine ratio were measured in women who developed pre-eclampsia and their matched controls. Comparisons between groups were performed using Student’s t test. Main outcome measures Development of pre-eclampsia. Results In the pre-eclampsia group, the median urinary PlGF concentration (20.6 pg/ml, interquartile range [IQR] 9.1–32.0 pg/ml) and median urinary PlGF to creatinine ratio (1.6 pg/mg, IQR 1.2–2.5 pg/mg) were not significantly different from the control group (11.8 pg/ml, IQR 5.5–29.8 pg/ml, P = 0.1 and 1.7 pg/mg, IQR 1.2–2.3 pg/mg, P = 0.3, respectively). There were no significant differences between women with early-onset pre-eclampsia requiring delivery before 34 weeks (n = 13) and those with late-onset pre-eclampsia (n = 39) and between women with pre-eclampsia and fetal growth restriction (FGR) (n = 25) and those with pre-eclampsia and no FGR (n = 27) in either median PlGF concentration or median urinary PlGF to creatinine ratio. Conclusions The development of pre-eclampsia is not preceded by altered urinary PlGF concentration in the first trimester of pregnancy. Keywords First trimester, PlGF, pre-eclampsia, pregnancy, urine. Please cite this paper as: Savvidou M, Akolekar R, Zaragoza E, Poon L, Nicolaides K. First trimester urinary placental growth factor and development of pre-eclampsia. BJOG 2009;116:643–647. Introduction Pre-eclampsia affects about 2% of pregnancies and is one of the leading causes of maternal and perinatal mortality and morbidity. 1 The widely accepted model of pre-eclampsia is that of impaired placental perfusion causing placental hyp- oxia and the release of factors, which trigger systemic mater- nal endothelial dysfunction and the clinical manifestation of the disease. 2,3 Recent evidence suggests that the placental fac- tors involved in the pathogenesis of pre-eclampsia are proan- giogenic factors (placental growth factor [PlGF] and vascular endothelial growth factor [VEGF]) and their inhibitor (solu- ble fms-like tyrosine kinase [sFlt-1]). 4,5 PIGF is involved in the regulation of placental vascular development during pregnancy. 6 Several studies reported reduced maternal serum and urinary PlGF concentration dur- ing the clinical phase of pre-eclampsia. 5,7–10 These decreased levels precede the clinical onset of the disease and are evident from the second trimester of pregnancy. 5,7 Recent studies have also reported reduced serum PlGF from as early as the first trimester. 5 The aims of this study were to assess the first trimester levels of urinary PlGF in women with normotensive pregnancies and women who subsequently developed pre-eclampsia and to evaluate its potential value in early screening for the disease. Methods Study participants This was a nested case–control study within our prospective study for early prediction of pre-eclampsia by maternal his- tory, uterine artery Doppler, mean arterial blood pressure ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 643 DOI: 10.1111/j.1471-0528.2008.02074.x www.blackwellpublishing.com/bjog Maternal medicine