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Terminal Complement Activation in Preeclampsia

Burwick, Richard M., MD, MPH; Velásquez, Jesús A., MD; Valencia, Catalina M., MD; Gutiérrez-Marín, Jorge, MD; Edna-Estrada, Francisco, MD; Silva, Jaime L., MD; Trujillo-Otálvaro, Juliana, MD; Vargas-Rodríguez, Johanna, MD; Bernal, Yamile, Bac; Quintero, Alvaro, MD; Rincón, Mónica, MD; Tolosa, Jorge E., MD, MSCE

doi: 10.1097/AOG.0000000000002980
Contents: Hypertension: Original Research

OBJECTIVE: To evaluate whether C5b-9 concentrations in blood and urine are increased in preeclampsia with severe features.

METHODS: The Complement and Preeclampsia in the Americas study is a prospective, multicenter case–control study performed at six centers in Colombia from November 2015 to July 2016. The case group included women with preeclampsia with severe features, and the control group included women who were healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. We enrolled two women in the control group for every woman in the case group. Soluble C5b-9 concentrations were measured by enzyme-linked immunosorbent assays in blood and urine. The primary outcome was C5b-9 concentrations in women in the case group compared with all women in the control group, and the secondary outcome was C5b-9 levels in women in the case group compared with individual control subgroups. Differences were assessed by test of medians, and associations were further evaluated by receiver operating characteristic curve analysis and logistic regression with α=0.05.

RESULTS: Three hundred fifty-two patients were enrolled. Plasma C5b-9 concentrations did not differ significantly between women in the case group and those in the control group, but urine C5b-9 concentrations were higher in women in the case group (median [interquartile range] 9.9 [1.6–43.7] vs 1.8 [0.54–4.1] ng/mL, P<.001). In subgroup analysis, plasma C5b-9 concentrations were increased in women in the case group compared with healthy women in the control group (median [interquartile range] 2,778 [1,633–4,230] vs 1,374 [1,064–2,332] ng/mL, P<.001), and urine C5b-9 concentrations were increased in women in the case group compared with all control subgroups (P<.001). Using receiver operating characteristic analysis, urine C5b-9 concentrations differentiated preeclampsia with severe features from hypertensive women in the control group (area under the receiver operating characteristic curve 0.74, 95% CI 0.68–0.80). Urine C5b-9 22 ng/mL or greater (range 0–158.4 ng/mL) was the optimal cut point for diagnosis of preeclampsia with severe features with adjusted odds ratio of 10.0 (95% CI 3.5–28.8, P<.001).

CONCLUSION: Urinary excretion of terminal complement effector C5b-9 is higher in women with preeclampsia with severe features compared with women with other hypertensive disorders of pregnancy and women without hypertension.

Increased urinary excretion of terminal complement effector C5b-9 differentiates preeclampsia with severe features from other hypertensive disorders of pregnancy.

Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon; the Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; FUNDARED-MATERNA, Bogotá, Universidad de Antioquia, Hospital Universitario San Vicente Fundación, and Universidad de Antioquia, Departamento de Obstetricia y Ginecología, NACER Salud Sexual y Reproductiva, Medellín, Clínica Reina Sofía Colsanitas SA, Bogotá, Clínica Universitaria Bolivariana, Universidad Pontificia Bolivariana, Medellín, ESE Clínica de Maternidad Rafael Calvo, Grupo de Investigación Maternidad Segura, Universidad de Cartagena, Cartagena, Hospital Universitario San Ignacio, Departamento de Ginecología y Obstetricia, Pontificia Universidad Javeriana, Bogotá, Hospital General de Medellín, Luz Castro de Gutiérrez ESE, Hospital Universitario, Medellín, and Laboratorio Clínico Sanitas, Clínica Colsanitas SA, Grupo de Investigación INPAC, Bogotá, Colombia.

Corresponding author: Richard M. Burwick, MD, MPH, Cedars-Sinai Medical Center, 8635 W 3rd Street, Medical Office Tower, Suite 160W, Los Angeles, CA 90048; email:

Supported by Colciencias, Administrative Department of Science, Technology and Innovation, Colombia, Código #111565740967; FUNDARED-MATERNA, and Oregon Health & Science University, Department of Obstetrics & Gynecology, Mission Award.

Financial Disclosure Dr. Burwick has served on the speaker's bureau for Alexion Pharmaceuticals. Dr. Burwick's role with Alexion was distinct from this research study, and Alexion was not involved in the concept, design, analysis, writing, or funding of this work in any manner. The other authors did not report any potential conflicts of interest.

Presented at the 38th Annual Meeting of the Society for Maternal-Fetal Medicine, January 29–February 3, 2018, Dallas, Texas.

For a list of contributors to Complement Activation in Preeclampsia in the Americas (COPA) study, see Appendix 1 online at

Each author has indicated that he or she has met the journal's requirements for authorship.

Peer review history is available at

Received July 12, 2018

Received in revised form September 08, 2018

Accepted September 20, 2018

© 2018 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.