Association between arterial stiffness and wave reflection with subsequent development of placental-mediated diseases during pregnancy: findings of a systematic review and meta-analysis Mohamed Waseem Osman a,c , Mintu Nath b , Eamonn Breslin a,c , Asma Khalil d , David R. Webb e , Thompson G. Robinson f , and Hatem A. Mousa a,c Objective: We present a comprehensive systematic review of published literature to examine, whether arterial stiffness and wave reflection measurements during pregnancy differed between healthy patients and patients with placental-mediated diseases including preeclampsia (PET), small for gestational age (SGA), fetal death, and placental abruption, and a quantitative assessment of the findings using the meta-analysis approach. Methods: We searched Medline, Embase, and The Cochrane Library for studies of arterial stiffness in pregnancy, analyzed pregnancy outcomes and conducted the meta-analysis of data evaluated by trimesters of pregnancy. Hemodynamic parameters evaluated included: pulse wave velocity (PWV), augmentation index (AIx), and augmentation index-75 (AIx-75). Results: We screened 2806 citations, reviewed 36 studies and included nine (n ¼ 15 923) studies for further quantitative assessment. Compared with healthy pregnancy, measures of arterial stiffness and wave reflection were consistently increased among pregnant women who subsequently developed PET during all trimesters. In the first trimester, mean AIx-75 (%) in the PET group was significantly higher with estimated standardized mean difference (SMD) of 0.90 [95% confidence intervals (95% CI) 0.07–1.73; P ¼ 0.034]. In the second trimester, the PET group had significantly higher PWV (m/s) with estimated SMD of 1.26 (95% CI 0.22–2.30; P ¼ 0.018). Concerning the SGA group, mean AIx (%) was greater during the second trimester only: 65.5 (SD 15.6) vs. 57.0 (11.2), P < 0.01. Conclusion: There is significant increase in arterial stiffness and wave reflection parameters among pregnant women who subsequently developed PET and SGA fetuses. Larger studies with consistent methodological designs are required to evaluate the role and usefulness of arterial stiffness and wave reflection measurements as a screening tool for placental-mediated diseases during pregnancy. Keywords: arterial stiffness, maternal hemodynamics, placental-mediated disease, pre-eclampsia, screening, small for gestational age Abbreviations: AIx, augmentation index; AIx-75, augmentation index adjusted to a heart rate of 75; IUFD, intrauterine fetal death; IUGR, intrauterine growth restriction; MoM, multiples of the median; PET, preeclampsia; PWA, pulse wave analysis; PWV, pulse wave velocity; sBPao, systolic blood pressure of the aorta; SGA, small for gestational age; SMD, standardized mean difference INTRODUCTION P reeclampsia (PET), fetal growth restriction (FGR), and placental abruption affect around a third of all pregnancies [1], and are associated with increased maternal and fetal morbidity and/or mortality worldwide. Of the 30 million growth-restricted infants born worldwide each year, 15% (4.5 million) are associated with PET [2] and an estimated half a million die because of PET [2]. There- fore, it would be ideal to screen women in early pregnancy to determine if the pregnancy is at risk for placental-medi- ated disease and individualize antenatal surveillance and timely delivery accordingly. Arterial stiffness measurements have proven to be an important predictor of cardiovascular risk and great interest has been shown in the role of arterial stiffness in the prediction of pregnancy complications and cardiovascular disease during pregnancy [3]. Pulse wave velocity (PWV) is Journal of Hypertension 2017, 35:000–000 a Department of Maternal and Fetal Medicine, University Hospitals of Leicester, Leicester, b Department of Cardiovascular Sciences and NIHR Biomedical Research Unit in Cardiovascular Disease, c University of Leicester, Leicester, d Department of Maternal and Fetal Medicine, St George’s University of London, London, e Diabetes Research Centre and f Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK Correspondence to Dr Hatem A. Mousa, MBCHB, MRCOG, MD, Consultant/ Honor- ary Senior Lecturer in Maternal and Fetal Medicine, Department of Maternal and Fetal Medicine, University Hospitals of Leicester, Kensington Building, Infirmary Close, Leicester LE1 5WW, UK. E-mail: Tommy.mousa@uhl-tr.nhs.uk Received 23 January 2017 Revised 6 November 2017 Accepted 2 December 2017 J Hypertens 35:000–000 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000001664 Journal of Hypertension www.jhypertension.com 1 Original Article Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.