Background-Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm (Ͻ32 weeks) preeclampsia. Methods and Results-We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27ϩ4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth. Conclusions-This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting. (Circulation. 2011;124:940-950.)Key Words: angiogenic factor Ⅲ apheresis Ⅲ preeclampsia P reeclampsia is a devastating medical complication of pregnancy associated with significant maternal and fetal morbidity and mortality. 1 The risk is highest in very preterm (Ͻ32 weeks) preeclampsia when the infant mortality rate is 70 times higher than at term. 2,3 Delivery of the placenta remains the only effective means to treat preeclampsia. Randomized trials have tested nonspecific interventions including antihypertensive agents; however, the ability of these and other interventions to prevent or stabilize the clinical manifestations and prolong pregnancy in preterm preeclampsia is limited. 4 -6 The underlying pathogenesis of preeclampsia has remained elusive, hampering successful development of targeted interventions for the condition. Clinical Perspective on p 950The prevailing hypothesis suggests that preeclampsia involves a placental factor that circulates to distal organs and causes damage to the vasculature. 7 We and others have suggested that excess placental derived soluble fms-like tyrosine kinase 1 (sFlt-1) or the soluble vascular endothelial growth factor (VEGF) receptor 1, an alternatively spliced variant of VEGF receptor 1, mediates the signs and symptoms of preeclampsia, and elevated circulating levels are associated with clinical preeclampsia. 8 -11 Circulating sFlt-1 levels in very preterm preeclampsia are among the highest obs...

The fetal ECG derived from abdominal leads provides an alternative to standard means of fetal monitoring. Furthermore, it permits long-term and ambulant recordings, which expands the range diagnostic possibilities for evaluating the fetal health state. However, due to the temporal and spectral overlap of maternal and fetal signals, the usage of abdominal leads imposes the need for elaborated signal processing routines.In this work a modular combination of processing techniques is presented. Its core consists of two maternal ECG estimation techniques, namely the extended Kalman smoother (EKS) and template adaption (TA) in combination with an innovative detection algorithm. Our detection method employs principles of evolutionary computing to detect fetal peaks by considering the periodicity and morphological characteristics of the fetal signal. In a postprocessing phase, single channel detections are combined by means of kernel density estimation and heart rate correction.The described methodology was presented during the Computing in Cardiology Challenge 2013. The entry was the winner of the closed-source events with average scores for events 4/5 with 15.1/3.32 (TA) and 69.5/4.58 (EKS) on training set-A and 20.4/4.57 (TA) and 219/7.69 (EKS) on test set-B, respectively. Using our own clinical data (24 subjects each 20 min recordings) and statistical measures beyond the Challenge's scoring system, we further validated the proposed method. For our clinical data we obtained an average detection rate of 82.8% (TA) and 83.4% (EKS). The achieved results show that the proposed methods are able produce reliable fetal heart rate estimates from a restricted number of abdominal leads.

Abstract-Abnormal uterine perfusion detected by Doppler sonography reflects impaired trophoblast invasion, a factor involved in the pathogenesis of pregnancy complications such as preeclampsia or intrauterine growth retardation. Recent studies have demonstrated an autoantibody against the angiotensin type 1 (AT 1 ) receptor in pregnant women with preeclampsia. Our aim was to determine whether the AT 1 autoantibody precedes the clinical symptoms and is thus predictive of preeclampsia. We therefore detected this antibody in serum from second trimester pregnancies with abnormal uterine perfusion because these women show an indirect sign of inadequate trophoblast invasion. Then the AT 1 autoantibody distribution/concentration was compared with that of women at term with or without pregnancy pathology. The AT 1 autoantibody was already detectable in second trimester pregnant women with abnormal uterine perfusion before the clinical manifestation of preeclampsia (80%). However, it was also found in second trimester pregnant women with abnormal uterine perfusion who later developed intrauterine growth retardation (60%) or even had a normal course of pregnancy (62%). In the third trimester, the AT 1 autoantibody was demonstrated in 89% of patients with manifest preeclampsia, 86% of those with manifest intrauterine growth retardation, and even in healthy pregnant women at term with a history of abnormal uterine perfusion in the second trimester. We conclude that the AT 1 autoantibody is an early but nonspecific marker for preeclampsia. The generation of this antibody seems to be associated with distinct types of pregnancy disorders resulting from impaired placental development. The AT 1 autoantibody may thus be causative for pathological uteroplacental perfusion. Key Words: angiotensin II Ⅲ antibodies Ⅲ hypertension, gestational Ⅲ preeclampsia Ⅲ pregnancy Ⅲ receptors, angiotensin P reeclampsia, a serious pregnancy-specific disorder characterized by proteinuria and hypertension after the 20th week of gestation, is still a leading cause of maternal and neonatal morbidity and mortality. The lack of preventive and causal treatment is mainly attributable to the fact that the etiology and pathophysiology are not understood. 1 Impairment of placental development and trophoblast invasion is thought to be causally associated with preeclampsia. Doppler ultrasound determination of uterine perfusion is a noninvasive tool for measuring uteroplacental vascular resistance and assessing the quality of the trophoblast invasion. 2 The trophoblast failed to develop adequately in pregnancies with abnormal uterine perfusion. Trophoblast invasion into the maternal compartment is thus impaired, and the pregnant uterus is not transformed into a low-resistance bed. Precisely this pathology is thought to be a pathogenetic feature of pregnancy complications such as preeclampsia or intrauterine growth retardation (IUGR). Abnormal uterine perfusion characterizes pregnancies at risk for these complications and precedes their clinical manifestation. H...