SYSTEMATIC REVIEWS AND META-ANALYSES Oral antioxidant therapy for prevention and treatment of preeclampsia: Meta-analysis of randomized controlled trials * M.B. Tenório a , R.C. Ferreira a , F.A. Moura a , N.B. Bueno a , M.O.F. Goulart b , A.C.M. Oliveira a, * a Faculdade de Nutrição, Universidade Federal de Alagoas, Campus A. C. Simões, BR 104 Norte, Km 96,7, Tabuleiro dos Martins, CEP 57.072-970, Maceió, Alagoas, Brazil b Instituto de Química e Biotecnologia (IQB/UFAL), Rede Nordeste de Biotecnologia (RENORBIO), Universidade Federal de Alagoas, Campus A. C. Simões, BR 104 Norte, Km 96,7, Tabuleiro dos Martins, CEP 57.072-970, Maceió, Alagoas, Brazil Received 30 January 2018; received in revised form 18 May 2018; accepted 4 June 2018 Handling Editor: A. Siani Available online --- KEYWORDS Antioxidant; Oral administration; Pregnant women; Preeclampsia Abstract Aims: To determine whether oral antioxidant therapies, of various types and doses, are able to prevent or treat women with preeclampsia. Data synthesis: The following databases were searched: MEDLINE, CENTRAL, LILACS, and Web of Science. Inclusion criteria were: a) randomized clinical trials; b) oral antioxidant supplementa- tion; c) study in pregnant women; d) control group, treated or not with placebo. Papers were excluded if they evaluated antioxidant nutrient supplementation associated with other non- antioxidant therapies. Data were extracted and the risk of bias of each study was assessed. Het- erogeneity was analyzed using the Cochran Q test, and I2 statistics and pre-specified sensitivity analyses were performed. Meta-analyses were conducted on prevention and treatment studies, separately. The primary outcome was the incidence of preeclampsia in prevention trials, and of perinatal death in treatment trials. Twenty-nine studies were included in the analysis, 19 for pre- vention and 10 for treatment. The antioxidants used in these studies were vitamins C and E, se- lenium, L-arginine, allicin, lycopene and coenzyme Q10, none of which showed beneficial effects on the prevention of preeclampsia (RR: 0.89, CI 95%: [0.79e1.02], P Z 0.09; I 2 Z 39%, P Z 0.04) and other outcomes. The antioxidants used in the treatment studies were vitamins C and E, N- acetylcysteine, L-arginine, and resveratrol. A beneficial effect was found in intrauterine growth restriction. Conclusions: Antioxidant therapy had no effects in the prevention of preeclampsia but did show beneficial effects in intrauterine growth restriction, when used in the treatment of this condition. ª 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Feder- ico II University. Published by Elsevier B.V. All rights reserved. Introduction Pregnancy is considered a sensitive period for the appearance of complications, such as hypertensive dis- eases and, particularly, preeclampsia (PE) [1,2]. This syn- drome is one of the leading causes of maternal and fetal mortality worldwide, together with hemorrhage and * This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. * Corresponding author. E-mail address: alanecabral@gmail.com (A.C.M. Oliveira). Please cite this article in press as: Tenório MB, et al., Oral antioxidant therapy for prevention and treatment of preeclampsia: Meta- analysis of randomized controlled trials, Nutrition, Metabolism & Cardiovascular Diseases (2018), https://doi.org/10.1016/ j.numecd.2018.06.002 https://doi.org/10.1016/j.numecd.2018.06.002 0939-4753/ª 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. Nutrition, Metabolism & Cardiovascular Diseases (2018) xx,1e 12 Available online at www.sciencedirect.com Nutrition, Metabolism & Cardiovascular Diseases journal homepage: www.elsevier.com/locate/nmcd