Angiogenic factors like placental growth factor and its antiangiogenic antagonist soluble fms-like tyrosine kinase 1 (sFlt1) are closely related to the pathogenesis of preeclampsia and intrauterine growth restriction. Because it is known that altered maternal sFlt1 and placental growth factor levels are detectable weeks before the onset of these pregnancy complications, it was the aim of the study to investigate the predictive value of these markers in high-risk second trimester pregnancies characterized by abnormal uterine perfusion. This prospective study includes 63 second trimester pregnant women with abnormal uterine perfusion. Twenty five of them developed a later complication (12 with preeclampsia, 11 with intrauterine growth restriction, and 2 with intrauterine death), whereas 38 had a normal course of pregnancy. Pregnancies with adverse pregnancy outcome showed in the second trimester significantly higher sFlt1 (1403.6+/-555 versus 451.8+/-42 pg/mL; P<0.05) and lower placental growth factor (139.6+/-24 versus 184.1+/-21 pg/mL) levels compared with those with normal outcome. These alterations were more pronounced in pregnancies with subsequent preeclampsia compared with intrauterine growth restriction and early onset diseases (delivery <34 weeks) compared with late-onset diseases. The combination of Doppler and sFlt1 increases the sensitivity of Doppler alone for iatrogenic preterm delivery from 64% up to 79% and the specificity from 63% up to 80%. Using both factors, sFlt1 and placental growth factor, early onset preeclampsia can be predicted with 83% sensitivity and 95% specificity. We conclude that the concurrent measurement of uterine perfusion and angiogenic factors allows an efficient prediction of early onset pregnancy complications, particularly preeclampsia.