Risk of preeclampsia and Vitamin C and E supplementation: a systematic review and meta-analysis
Keywords:
pre-Eclampsia, vitamin C, vitamin E, disease prevention.Abstract
Introduction: It has been suggested that preeclampsia can be prevented by vitamin E and C intake, given the pathophysiological mechanism of this disease.Objective: To determine the joint efficacy of vitamin C and E in the prevention of preeclampsia.
Methods: Systematic review of randomized clinical trials. A search of pubmed/medline, SCOPUS, Web of Science, Cochrane Library, EMBASE, and Clinical Trials databases was performed. The risk of bias of the randomized clinical trials was assessed using the Cochrane tool version 2. A random-effects meta-analysis was performed and relative risks were calculated, with corresponding 95 % confidence intervals.
Results: Seven studies were included (n= 1 475). No statistically significant association of treatment with vitamin C and E supplementation was found with respect to preeclampsia (relative risks: 1.03; 95 % CI 0.78-1.26).
Conclusions: Dual vitamin C and E supplementation does not prevent preeclampsia in pregnant women at risk for the disease.
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References
1. ACOG. Clinical Management Guidelines for Obstetrician - Gynecologists. Obstetrics & Gynecology. 2019; 133(76):168-86. DOI: 10.1097/00006250-200610000-00046
2. Norwitz ER, Repke JT. Preeclampsia Prevention and Management. Journal of the Society for Gynecologic Investigation. 2000; 7(1):21-36. DOI: 10.1177/107155760000700105
3. Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia Pathophysiology and Clinical Presentations: JACC State of the Art Review. Journal of the American College of Cardiology. 2020; 76(14):1690-702. DOI: 10.1016/j.jacc.2020.08.014
4. Kirby Ojeda CP. Síndrome hipertensivo del embarazo en Ecuador y Latinoamérica [Tesis universitaria]. Machala: Universidad Técnica de Machala; 2019. [acceso: 16/09/2021]. Disponible en: http://repositorio.utmachala.edu.ec/handle/48000/13616
5. Cantillano Aburto VM., Meléndez AIO. Factores de riesgo asociados a Preclampsia-eclampsia en mujeres hospitalizadas en el Hospital Alemán Nicaragüense, durante el periodo comprendido de noviembre 2018 a febrero del 2019 [Tesis Universitaria]. Managua: Universidad Nacional Autónoma de Nicaragua; 2019. [acceso: 16/09/2021]. Disponible en: https://repositorio.unan.edu.ni/11144/
6. Vasquez Martinez J. Prevalencia De Preeclampsia En Embarazadas En El Servicio De Ginecologia Y Obstetricia Del Hospital Central Del Instituto De Previsión Social, 2017; 2018 [Trabajo de fin de grado]. Paraguay: Universidad Nacional de Caaguazú, Facultad de Ciencias Médicas; 2018. [acceso: 16/09/2021]. Disponible en: https://docs.bvsalud.org/biblioref/2019/10/1021596/prevalencia-de-preeclampsia-en-embarazadas-en-el-servicio-de-g_rJ6BEgR.pdf
7. Herrrera MM. Mortalidad materna en el mundo. Revista chilena de obstetricia y ginecología. 2003; 68(6):536-43. DOI:10.4067/S0717-75262003000600015
8. Guevara Rios E. Impacto de la pandemia en la salud materna en el Perú. The Lancet Global Health. 2014; 2(6):334-45. DOI: 10.33421/inmp.2021230
9. Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Supplementation with vitamins C and e during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: A systematic review and metaanalysis. American Journal of Obstetrics and Gynecology. 2011; 204(6):503.e1-503.e12. DOI: 10.1016/j.ajog.2011.02.020
10. Spinnato JA, Freire S, Pinto JL, Rudge MC, Martins-Costa S, Koch MA, et al. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol. 2004; 24(6 SPEC.ISS.):557-64. DOI: 10.1097/01.AOG.0000289576.43441.1f
11. Xu H, Perez-Cuevas R, Xiong X, Reyes H, Roy C, Julien P, et al. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). American Journal of Obstetrics and Gynecology. 2010; 202(3):239.e1-239.e10. DOI: 10.1016/j.ajog.2010.01.050
12. Roberts JM, Myatt L, Spong CY, Thom EA, John C . Hauth, Leveno KJ, et al. Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension. N Engl J Med. 2005; 23(1):1-7. DOI: 10.1056/NEJMoa0908056
13. Villar J, Purwar M, Merialdi M, Zavaleta N, Thi Nhu Ngoc N, Anthony J, et al. World Health Organisation multicentre randomised trial of supplementation with vitamins C and e among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009; 116(6):780-8. DOI: 10.1111/j.1471-0528.2009.02158.x
14. Poston L, Raijmakers M, Kelly F. Vitamin E in preeclampsia. Annals of the New York Academy of Sciences. 2004; 1031(44):242-8. DOI: 10.1196/annals.1331.024
15. Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database of Systematic Reviews. 2015; (9):CD004069. DOI: 10.1002/14651858.CD004069.pub3
16. Kiondo P, Wamuyu-Maina G, Wandabwa J, Bimenya GS, Tumwesigye NM, Okong P. The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: A randomized placebo controlled clinical trial. BMC Pregnancy and Childbirth. 2014; 14(1):1-10. DOI: 10.1186/1471-2393-14-283
17. Castillo Velarde ER. Vitamina C En La Salud Y En La Enfermedad. Revista de la Facultad de Medicina Humana. 2019; 19(4):95-100. DOI: 10.25176/rfmh.v19i4.2351
18. Taravati A, Tohidi F. Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwanese Journal of Obstetrics and Gynecology. 2018; 57(6):779-90. DOI:10.1016/j.tjog.2018.10.002
19. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. DOI: 10.1371/journal.pmed.1000097
20. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JA. Assessing risk of bias in a randomized trial. En: Higgins PT, Thomas J, Chandler J, Cumpston M, Li T, Matthew J, et al (editors). Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Ltd; 2019. [acceso: 20/01/22]. p. 205-28. DOI: 10.1002/9781119536604.ch8
21. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186
22. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. John Wiley & Sons; 2019. [acceso 27/09/2021]. DOI:10.1002/9780470712184
23. Organización Mundial de la Salud. Recomendaciones de la OMS para la prevención y el tratamiento de la preeclampsia y la eclampsia. Ginebra: Organización Mundial de la Salud; 2014. [acceso: 27/09/2021]. Disponible en: https://apps.who.int/iris/bitstream/handle/10665/138405/9789243548333_spa.pdf
24. Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Supplementation with vitamins C and e during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: A systematic review and metaanalysis. American Journal of Obstetrics and Gynecology. 2011; 204(6):503.e1-503.e12. DOI: 10.1016/j.ajog.2011.02.020
25. Polyzos NP, Mauri D, Tsappi M, Tzioras S, Kamposioras K, Cortinovis I, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: A systematic review. Obstetrical and Gynecological Survey. 2007; 62(3):202-6. DOI: 10.1097/01.ogx.0000256787.04807.da
26. Beazley D, Ahokas R, Livingston J, Griggs M, Sibai BM. Vitamin C and E supplementation in women at high risk for preeclampsia: A double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology. 2005; 192(2):520-1. DOI: 10.1016/j.ajog.2004.09.005
27. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS. Vitamins C and E and the Risks of Preeclampsia and Perinatal Complications. New England Journal of Medicine. 2006; 354(17):1796-806. DOI: 10.1056/nejmoa054186
28. Sánchez-Valle V, Méndez-Sánchez N. Estrés oxidativo, antioxidantes y enfermedad. Artículo de revisión. Rev Invest Med Sur Mex. 2013 [acceso: 27/09/2021]; 20(3):161-8. Disponible en: https://xdoc.mx/documents/estres-oxidativo-antioxidantes-y-enfermedad-600669ad79293
29. Khaing W, Vallibhakara SAO, Tantrakul V, Vallibhakara O, Rattanasiri S, McEvoy M, et al. Calcium and vitamin D supplementation for prevention of preeclampsia: A systematic review and network meta-analysis. Nutrients. 2017; 9(10):1-23. DOI: 10.3390/nu9101141
30. Fogacci S, Fogacci F, Banach M, Michos ED, Hernandez A V., Lip GYH, et al. Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials. Clinical Nutrition. 2020; 39(6):1742-52. DOI: 10.1016/j.clnu.2019.08.015
31. Perichart-Perera O, Rodríguez-Cano AM, Gutiérrez-Castrellón P. Relevance of nutritional supplements during pregnancy: Role of iron, folic acid, vitamin d, calcium and multiple micronutrients. Gaceta Medica de Mexico. 2020; 156(Supl 3):S1-26. DOI: 10.24875/GMM.M20000434
32. Dakhale GN, Chaudhari H V., Shrivastava M. Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: A randomized, double-blind study. Advances in Pharmacological Sciences. 2011; 2011. DOI: 10.1155/2011/195271
33. Lee HS. Impact of maternal diet on the epigenome during in utero life and the developmental programming of diseases in childhood and adulthood. Nutrients. 2015; 7(11):9492-507. DOI: 10.3390/nu7115467
2. Norwitz ER, Repke JT. Preeclampsia Prevention and Management. Journal of the Society for Gynecologic Investigation. 2000; 7(1):21-36. DOI: 10.1177/107155760000700105
3. Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia Pathophysiology and Clinical Presentations: JACC State of the Art Review. Journal of the American College of Cardiology. 2020; 76(14):1690-702. DOI: 10.1016/j.jacc.2020.08.014
4. Kirby Ojeda CP. Síndrome hipertensivo del embarazo en Ecuador y Latinoamérica [Tesis universitaria]. Machala: Universidad Técnica de Machala; 2019. [acceso: 16/09/2021]. Disponible en: http://repositorio.utmachala.edu.ec/handle/48000/13616
5. Cantillano Aburto VM., Meléndez AIO. Factores de riesgo asociados a Preclampsia-eclampsia en mujeres hospitalizadas en el Hospital Alemán Nicaragüense, durante el periodo comprendido de noviembre 2018 a febrero del 2019 [Tesis Universitaria]. Managua: Universidad Nacional Autónoma de Nicaragua; 2019. [acceso: 16/09/2021]. Disponible en: https://repositorio.unan.edu.ni/11144/
6. Vasquez Martinez J. Prevalencia De Preeclampsia En Embarazadas En El Servicio De Ginecologia Y Obstetricia Del Hospital Central Del Instituto De Previsión Social, 2017; 2018 [Trabajo de fin de grado]. Paraguay: Universidad Nacional de Caaguazú, Facultad de Ciencias Médicas; 2018. [acceso: 16/09/2021]. Disponible en: https://docs.bvsalud.org/biblioref/2019/10/1021596/prevalencia-de-preeclampsia-en-embarazadas-en-el-servicio-de-g_rJ6BEgR.pdf
7. Herrrera MM. Mortalidad materna en el mundo. Revista chilena de obstetricia y ginecología. 2003; 68(6):536-43. DOI:10.4067/S0717-75262003000600015
8. Guevara Rios E. Impacto de la pandemia en la salud materna en el Perú. The Lancet Global Health. 2014; 2(6):334-45. DOI: 10.33421/inmp.2021230
9. Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Supplementation with vitamins C and e during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: A systematic review and metaanalysis. American Journal of Obstetrics and Gynecology. 2011; 204(6):503.e1-503.e12. DOI: 10.1016/j.ajog.2011.02.020
10. Spinnato JA, Freire S, Pinto JL, Rudge MC, Martins-Costa S, Koch MA, et al. Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol. 2004; 24(6 SPEC.ISS.):557-64. DOI: 10.1097/01.AOG.0000289576.43441.1f
11. Xu H, Perez-Cuevas R, Xiong X, Reyes H, Roy C, Julien P, et al. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). American Journal of Obstetrics and Gynecology. 2010; 202(3):239.e1-239.e10. DOI: 10.1016/j.ajog.2010.01.050
12. Roberts JM, Myatt L, Spong CY, Thom EA, John C . Hauth, Leveno KJ, et al. Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension. N Engl J Med. 2005; 23(1):1-7. DOI: 10.1056/NEJMoa0908056
13. Villar J, Purwar M, Merialdi M, Zavaleta N, Thi Nhu Ngoc N, Anthony J, et al. World Health Organisation multicentre randomised trial of supplementation with vitamins C and e among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009; 116(6):780-8. DOI: 10.1111/j.1471-0528.2009.02158.x
14. Poston L, Raijmakers M, Kelly F. Vitamin E in preeclampsia. Annals of the New York Academy of Sciences. 2004; 1031(44):242-8. DOI: 10.1196/annals.1331.024
15. Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database of Systematic Reviews. 2015; (9):CD004069. DOI: 10.1002/14651858.CD004069.pub3
16. Kiondo P, Wamuyu-Maina G, Wandabwa J, Bimenya GS, Tumwesigye NM, Okong P. The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: A randomized placebo controlled clinical trial. BMC Pregnancy and Childbirth. 2014; 14(1):1-10. DOI: 10.1186/1471-2393-14-283
17. Castillo Velarde ER. Vitamina C En La Salud Y En La Enfermedad. Revista de la Facultad de Medicina Humana. 2019; 19(4):95-100. DOI: 10.25176/rfmh.v19i4.2351
18. Taravati A, Tohidi F. Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwanese Journal of Obstetrics and Gynecology. 2018; 57(6):779-90. DOI:10.1016/j.tjog.2018.10.002
19. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. DOI: 10.1371/journal.pmed.1000097
20. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JA. Assessing risk of bias in a randomized trial. En: Higgins PT, Thomas J, Chandler J, Cumpston M, Li T, Matthew J, et al (editors). Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Ltd; 2019. [acceso: 20/01/22]. p. 205-28. DOI: 10.1002/9781119536604.ch8
21. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186
22. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. John Wiley & Sons; 2019. [acceso 27/09/2021]. DOI:10.1002/9780470712184
23. Organización Mundial de la Salud. Recomendaciones de la OMS para la prevención y el tratamiento de la preeclampsia y la eclampsia. Ginebra: Organización Mundial de la Salud; 2014. [acceso: 27/09/2021]. Disponible en: https://apps.who.int/iris/bitstream/handle/10665/138405/9789243548333_spa.pdf
24. Conde-Agudelo A, Romero R, Kusanovic JP, Hassan SS. Supplementation with vitamins C and e during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: A systematic review and metaanalysis. American Journal of Obstetrics and Gynecology. 2011; 204(6):503.e1-503.e12. DOI: 10.1016/j.ajog.2011.02.020
25. Polyzos NP, Mauri D, Tsappi M, Tzioras S, Kamposioras K, Cortinovis I, et al. Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: A systematic review. Obstetrical and Gynecological Survey. 2007; 62(3):202-6. DOI: 10.1097/01.ogx.0000256787.04807.da
26. Beazley D, Ahokas R, Livingston J, Griggs M, Sibai BM. Vitamin C and E supplementation in women at high risk for preeclampsia: A double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology. 2005; 192(2):520-1. DOI: 10.1016/j.ajog.2004.09.005
27. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS. Vitamins C and E and the Risks of Preeclampsia and Perinatal Complications. New England Journal of Medicine. 2006; 354(17):1796-806. DOI: 10.1056/nejmoa054186
28. Sánchez-Valle V, Méndez-Sánchez N. Estrés oxidativo, antioxidantes y enfermedad. Artículo de revisión. Rev Invest Med Sur Mex. 2013 [acceso: 27/09/2021]; 20(3):161-8. Disponible en: https://xdoc.mx/documents/estres-oxidativo-antioxidantes-y-enfermedad-600669ad79293
29. Khaing W, Vallibhakara SAO, Tantrakul V, Vallibhakara O, Rattanasiri S, McEvoy M, et al. Calcium and vitamin D supplementation for prevention of preeclampsia: A systematic review and network meta-analysis. Nutrients. 2017; 9(10):1-23. DOI: 10.3390/nu9101141
30. Fogacci S, Fogacci F, Banach M, Michos ED, Hernandez A V., Lip GYH, et al. Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials. Clinical Nutrition. 2020; 39(6):1742-52. DOI: 10.1016/j.clnu.2019.08.015
31. Perichart-Perera O, Rodríguez-Cano AM, Gutiérrez-Castrellón P. Relevance of nutritional supplements during pregnancy: Role of iron, folic acid, vitamin d, calcium and multiple micronutrients. Gaceta Medica de Mexico. 2020; 156(Supl 3):S1-26. DOI: 10.24875/GMM.M20000434
32. Dakhale GN, Chaudhari H V., Shrivastava M. Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: A randomized, double-blind study. Advances in Pharmacological Sciences. 2011; 2011. DOI: 10.1155/2011/195271
33. Lee HS. Impact of maternal diet on the epigenome during in utero life and the developmental programming of diseases in childhood and adulthood. Nutrients. 2015; 7(11):9492-507. DOI: 10.3390/nu7115467
Published
2022-09-15
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Perdomo Rebaza MT, Vera-Ponce VJ, Torres-Malca JR, Talavera JE, Zuzunaga-Montoya FE, De La Cruz-Vargas JA. Risk of preeclampsia and Vitamin C and E supplementation: a systematic review and meta-analysis. Rev Cubana Med Milit [Internet]. 2022 Sep. 15 [cited 2025 Apr. 3];51(3):e02202098. Available from: https://revmedmilitar.sld.cu/index.php/mil/article/view/2098
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