The role of vitamin D in reducing the risk of preeclampsia: a systematic literature review
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20262129Keywords:
Vitamin D, Preeclampsia, Pregnancy, Vitamin D deficiency, Maternal outcomesAbstract
Preeclampsia is a major cause of maternal and fetal complications worldwide. Vitamin D has been suggested as a possible factor that may influence its development, but existing evidence is inconsistent. To evaluate the association between vitamin D and the risk of preeclampsia and to assess the effect of vitamin D supplementation during pregnancy. A systematic review was conducted following PRISMA 2020 guidelines. Studies published from 2012 to 2026 were searched in PubMed, Scopus, Web of Science, EMBASE, Cochrane Library and Google Scholar. Keywords included “vitamin D,” “preeclampsia,” “pregnancy-induced hypertension,” and “supplementation”. Eligible studies included randomized controlled trials, cohort studies and case-control studies involving pregnant women. Data on study design, vitamin D exposure and outcomes were extracted. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane tool. Fifteen studies were included. Most observational studies showed that low vitamin D levels were linked with a higher risk of preeclampsia. Several trials reported that high-dose or early supplementation reduced risk, especially in deficient or high-risk women. However, some studies found no clear benefit, particularly with low doses or late pregnancy supplementation. The findings were inconsistent due to differences in dose, timing and baseline vitamin D status. Low vitamin D levels may increase the risk of preeclampsia. Supplementation appears beneficial mainly when started early and in deficient women. However, evidence is not fully consistent. More large and well-designed trials are needed to establish clear clinical recommendations for vitamin D use in pregnancy.
Metrics
References
Martini C, Saeed Z, Simeone P, Palma S, Ricci M, Arata A, et al. Preeclampsia: Insights into pathophysiological mechanisms and preventive strategies. Am J Prev Cardiol. 2025;23:101054. DOI: https://doi.org/10.1016/j.ajpc.2025.101054
Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia—pathophysiology and clinical presentations. J Am Coll Cardiol. 2020;76(14):1690-702. DOI: https://doi.org/10.1016/j.jacc.2020.08.014
Sasan SB, Zandvakili F, Soufizadeh N, Baybordi E. The effects of vitamin D supplementation on prevention of recurrence of preeclampsia in pregnant women with a history of preeclampsia. Obstet Gynecol Int. 2017;2017:8249264. DOI: https://doi.org/10.1155/2017/8249264
AlSubai A, Baqai MH, Agha H, Shankarlal N, Javaid SS, Jesrani EK, et al. Vitamin D and preeclampsia: a systematic review and meta-analysis. SAGE Open Med. 2023;11:20503121231212093. DOI: https://doi.org/10.1177/20503121231212093
Alimoradi Z, Kazemi F, Tiznobeik A, Griffiths MD, Masoumi SZ, Aghababaei S. The effect of vitamin D supplementation in pregnancy on the incidence of preeclampsia: a systematic review and meta-analysis. Eur J Integr Med. 2024;66:102343. DOI: https://doi.org/10.1016/j.eujim.2024.102343
Chang KJ, Seow KM, Chen KH. Preeclampsia: recent advances in predicting, preventing, and managing the maternal and fetal life-threatening condition. Int J Environ Res Public Health. 2023;20(4):2994. DOI: https://doi.org/10.3390/ijerph20042994
Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiology. Cardiovasc J Afr. 2016;27(2):71-8. DOI: https://doi.org/10.5830/CVJA-2016-009
Torres-Torres J, Espino y Sosa S, Martinez-Portilla R, Borboa-Olivares H, Estrada-Gutierrez G, Acevedo-Gallegos S, et al. A narrative review on the pathophysiology of preeclampsia. Int J Mol Sci. 2024;25(14):7569. DOI: https://doi.org/10.3390/ijms25147569
Gusella A, Martignoni G, Giacometti C. Behind the curtain of abnormal placentation in pre-eclampsia: from molecular mechanisms to histological hallmarks. Int J Mol Sci. 2024;25(14):7886. DOI: https://doi.org/10.3390/ijms25147886
Papapanagiotou A, Daskalaki MA, Gargalionis AN, Margoni A, Domali A, Daskalakis G, et al. The role of angiogenetic factors in preeclampsia. Int J Mol Sci. 2025;26(21):10431. DOI: https://doi.org/10.3390/ijms262110431
Kokkinari A, Antoniou E, Orovou E, Andronikidi PE, Tzitiridou-Chatzopoulou M, Sarantaki A, et al. The role of vitamin D supplementation in preventing pre-eclampsia: a review of randomized controlled trials with meta-analysis. Healthcare. 2025;13(11):1221. DOI: https://doi.org/10.3390/healthcare13111221
Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of vitamin D in pregnancy and lactation: emerging concepts. Women’s Health (Lond). 2012;8(3):323-40. DOI: https://doi.org/10.2217/WHE.12.17
Cyprian F, Lefkou E, Varoudi K, Girardi G. Immunomodulatory effects of vitamin D in pregnancy and beyond. Front Immunol. 2019;10:2739. DOI: https://doi.org/10.3389/fimmu.2019.02739
Subramanian A, Carr CM, Papp E, Murphy KE, Al Mahmud A, Roth DE, et al. Effect of vitamin D₃ supplementation starting mid-pregnancy on placental angiogenic factors and terminal villi: a secondary analysis of a randomized controlled trial in Bangladesh. BMC Pregnancy Childbirth. 2025;25(1):752. DOI: https://doi.org/10.1186/s12884-025-07566-4
Burris HH, Rifas-Shiman SL, Huh SY, Kleinman K, Litonjua AA, Oken E, et al. Vitamin D status and hypertensive disorders in pregnancy. Ann Epidemiol. 2014;24(5):399-403. DOI: https://doi.org/10.1016/j.annepidem.2014.02.001
Faulkner JL, Amaral LM, Cornelius DC, Cunningham MW, Ibrahim T, Heep A, et al. Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia, including hypertension. Am J Physiol Regul Integr Comp Physiol. 2017;312(1):R125-31. DOI: https://doi.org/10.1152/ajpregu.00218.2016
Mirzakhani H, Litonjua AA, McElrath TF, O’Connor G, Lee-Parritz A, Iverson R, et al. Early pregnancy vitamin D status and risk of preeclampsia. J Clin Invest. 2016;126(12):4702-15. DOI: https://doi.org/10.1172/JCI89031
Parul S, Anuj AP, Harbans L, Smiti N. Benefits of vitamin D supplementation in pregnancy for prevention of preeclampsia. Int J Pharm Biol Sci. 2012;2(3):144-50.
Yap C, Cheung NW, Gunton JE, Athayde N, Munns CF, Duke A, et al. Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial. Diabetes Care. 2014;37(7):1837-44. DOI: https://doi.org/10.2337/dc14-0155
Corcoy R, Mendoza LC, Simmons D, Desoye G, Adelantado JM, Chico A, et al. The DALI vitamin D randomized controlled trial for gestational diabetes mellitus prevention: no major benefit shown besides vitamin D sufficiency. Clin Nutr. 2020;39(3):976-84. DOI: https://doi.org/10.1016/j.clnu.2019.04.006
Xiaomang J, Yanling W. Effect of vitamin D₃ supplementation during pregnancy on high-risk factors: a randomized controlled trial. J Perinat Med. 2021;49(4):480-4. DOI: https://doi.org/10.1515/jpm-2020-0318
Naghshineh E, Sheikhaliyan S. Effect of vitamin D supplementation in reducing the risk of preeclampsia in nulliparous women. Adv Biomed Res. 2016;5:7. DOI: https://doi.org/10.4103/2277-9175.175239
Kabuyanga RK, Tugirimana PL, Sifa B, Balezi M, Dikete ME, Mitangala PN, et al. Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women: a randomized clinical trial in Eastern Democratic Republic of the Congo. BMC Pregnancy Childbirth. 2024;24(1):107. DOI: https://doi.org/10.1186/s12884-024-06277-6
Bener A, Al-Hamaq AO, Saleh NM. Association between vitamin D insufficiency and adverse pregnancy outcomes: global comparisons. Int J Womens Health. 2013;5:523-31. DOI: https://doi.org/10.2147/IJWH.S51403
Asemi Z, Esmaillzadeh A. The effect of multi mineral-vitamin D supplementation on pregnancy outcomes in pregnant women at risk for pre-eclampsia. Int J Prev Med. 2015;6:62. DOI: https://doi.org/10.4103/2008-7802.160975
Alkhalaf ZM, Mumford SL, Shenassa ED, Schisterman EF, Silver RM, Thoma ME. Preconception vitamin D status and subsequent risk of preeclampsia: a secondary cohort analysis from the EAGeR trial. Pregnancy Hypertens. 2026;43:101417. DOI: https://doi.org/10.1016/j.preghy.2026.101417
Saima A, Arooj FK, Kiran F, Muhammad I. The effects of vitamin D supplementation on prevention of preeclampsia in pregnant women. Isr Med J. 2023;15(1):11-4. DOI: https://doi.org/10.55282/imj.oa1370
Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of high-dose vitamin D supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Horm Metab Res. 2015;47(12):867-72. DOI: https://doi.org/10.1055/s-0035-1548835
Lee JY, Jung SH, Ahn EH, Ryu HM. Assessing the influence of maternal vitamin D deficiency in early pregnancy and subsequent improvement on perinatal outcomes and long-term child development: a retrospective cohort study. PLoS One. 2025;20(5):e0323146. DOI: https://doi.org/10.1371/journal.pone.0323146
Das B, Singhal SR, Ghalaut VS. Evaluating the association between maternal vitamin D deficiency and preeclampsia among Indian gravidas. Eur J Obstet Gynecol Reprod Biol. 2021;261:103-9. DOI: https://doi.org/10.1016/j.ejogrb.2021.04.014