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.
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.
Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia—pathophysiology and clinical presentations. J Am Coll Cardiol. 2020;76(14):1690-702.
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.
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.
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.
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.
Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiology. Cardiovasc J Afr. 2016;27(2):71-8.
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.
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.
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.
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.
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.
Cyprian F, Lefkou E, Varoudi K, Girardi G. Immunomodulatory effects of vitamin D in pregnancy and beyond. Front Immunol. 2019;10:2739.
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.
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.
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.
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.
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.
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.
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.
Naghshineh E, Sheikhaliyan S. Effect of vitamin D supplementation in reducing the risk of preeclampsia in nulliparous women. Adv Biomed Res. 2016;5:7.
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.
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.
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.
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.
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.
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.
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.
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.
Downloads
Published
How to Cite
Issue
Section
