Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. A combined technique for predicting pre-eclampsia: concurrent measurement of uterine perfusion and analysis of heart rate and blood pressure variability Thomas Walther a,b , Niels Wessel c , Hagen Malberg d , Andreas Voss e , Holger Stepan f and Renaldo Faber f Objective Pre-eclampsia is a serious complication of pregnancy with high morbidity and mortality and an incidence of 3 – 5% in all pregnancies. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients have pathological uterine perfusion in the second trimester, perfusion disturbance has a positive predictive accuracy (PPA) only of approximately 30%. Methods Non-invasive continuous blood pressure recordings were taken simultaneously via a finger cuff for 30 min. Time series of systolic as well as diastolic beat-to- beat pressure values were extracted to analyse heart rate and blood pressure variability and baroreflex sensitivity in 102 second-trimester pregnancies, to assess predictability for pre-eclampsia (n U 16). All women underwent Doppler investigations of the uterine arteries. Results We identified a combination of three variability and baroreflex parameters to best predict pre-eclampsia several weeks before clinical manifestation. The discriminant function of these three parameters classified patients with later pre-eclampsia with a sensitivity of 87.5%, a specificity of 83.7%, and a PPA of 50.0%. Combined with Doppler investigations of uterine arteries, PPA increased to 71.4%. Conclusions This technique of incorporating one-stop clinical assessment of uterine perfusion and variability parameters in the second trimester produces the most effective prediction of pre-eclampsia to date. J Hypertens 24:747–750 Q 2006 Lippincott Williams & Wilkins. Journal of Hypertension 2006, 24:747–750 Keywords: blood pressure variability, Doppler sonography, heart rate variability, prediction, pre-eclampsia a Department of Cardiology, Charite ´ , Campus Benjamin Franklin (CBF), Berlin, Germany, b Department of Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands, c Department of Physics, University of Potsdam, d Karlsruhe Research Center, Institute for Applied Computer Science, Karlsruhe, e Department of Medical Engineering, University of Applied Sciences, Jena and f Department of Obstetrics and Gynecology, University of Leipzig, Germany Correspondence and requests for reprints to Renaldo Faber MD, Universita ¨ tsfrauenklinik Philipp-Rosenthalstr. 55, 04103 Leipzig, Germany Tel: +49 341 9723 595; fax: +49 341 9723 669; e-mail: renaldo.faber@medizin.uni-leipzig.de Received 16 August 2005 Revised 16 December 2005 Accepted 20 December 2005 Introduction Pre-eclampsia, a serious pregnancy-specific disorder characterized by proteinuria and hypertension after the 20th week of gestation, is still the main cause of maternal and neonatal morbidity and mortality. It occurs in 3–5% of all pregnancies. As the aetiology and pathogenetic factors underlying this complication of pregnancy are still unknown, the aim of early risk assessment by Doppler sonography is to improve clinical management and out- come. However, the positive predictive value of Doppler sonography is limited to approximately 30%, as only a proportion of women with disturbed uterine perfusion develop one of the complications of pregnancy, such as pre-eclampsia (PE), pregnancy-induced hypertension (PIH), or intrauterine growth retardation (IUGR) [1]. Previous studies have failed to identify an independent marker in maternal plasma, or an easy to measure phys- iological parameter which would substantially improve the screening efficacy of Doppler sonography [2,3]. Analyses of heart rate (HRV) and blood pressure varia- bility (BPV), and baroreflex sensitivity (BRS), have become powerful techniques for assessing autonomic control in cardiovascular diseases [4,5]. Some preliminary studies of hypertensive disorders of pregnancy, such as pregnancies with chronic hypertension [6], gestational hypertension [7] or pre-eclampsia [7–9], in particular, illustrated the power of these parameters in describing the pathological cardiovascular alterations at a time when the diseases are manifest. We considered the possibility of a combination of this technique with Doppler sonography being able to improve the prediction of pre-eclampsia. As impedance measurement in utero-pla- cental circulation is able to detect later diseases in the course of pregnancy, but overclassifies patients, we inves- tigated the concurrent application of Doppler sonography and the assessment of maternal autonomic regulation as a clinically practicable and useful approach to predicting pre-eclampsia. Methods The study included 58 patients with abnormal uterine perfusion (AUP) examined consecutively, and 44 normal pregnancies recruited in parallel, who underwent Doppler sonography in the second trimester of pregnancy Original article 747 0263-6352 ß 2006 Lippincott Williams & Wilkins