The comparison between folic acid supplementation compared to calcium supplementation as preeclampsia prevention: a systematic review

Chelsie Angelius; Fuad Gandhi Torizal

doi:10.31101/ijhst.v6i1.3684

Authors

Chelsie Angelius Universitas Pelita Harapan, Tangerang, Banten, Indonesia
Fuad Gandhi Torizal Universitas Aisyiyah Yogyakarta, Indonesia, Indonesia

DOI:

https://doi.org/10.31101/ijhst.v6i1.3684

Keywords:

Calcium, Folic Acid, Preeclampsia, Pregnant woman

Abstract

Preeclampsia is a major cause of adverse pregnancy outcomes for both mothers and infants, leading to higher rates of morbidity and mortality. Despite progress in prenatal care, the exact cause of Preeclampsia remains unknown, highlighting the need for effective prevention strategies to improve outcomes. Various nutritional interventions can be used as potential preventive measures against Preeclampsia. Among these, folic acid and calcium supplementation have garnered considerable attention. This systematic review aims to compare the effectiveness of folic acid versus calcium supplementation in preventing Preeclampsia. By synthesizing the current evidence, we seek to elucidate the relative benefits of these two interventions, thereby providing clearer guidance for clinical practice and future research. This systematic review uses PubMed Central, Springerlink, PubMed, and Google Scholar as databases, using MeSH (Medical Subject Headings) terms: ‘Folic Acid’, ‘Calcium’, and ‘Preeclampsia’ to extract relevant publications. Publications included were limited to English publications in the past 5 years globally. This study included 6 studies compromising 29.664 women. Prisma table is used to identify studies via databased and sorted with Rayyan.ai. Both Calcium and Folic acid supplementation in adequate dose equally needed to prevent preeclampsia. Further research is necessary to evaluate the effectiveness of therapy in equivalent subject groups. There is currently limited information on the impact of health supplements on high-risk pregnancies, including the effects of calcium supplementation.

References

Abreu, A. M., Young, R. R., Buchanan, A., Lofgren, I. E., Okronipa, H. E., Lartey, A., ... & Oaks, B. M. (2021). Maternal Blood Pressure in Relation to Prenatal Lipid-Based Nutrient Supplementation and Adverse Birth Outcomes in a Ghanaian Cohort: A Randomized Controlled Trial and Cohort Analysis. The Journal of nutrition, 151(6), 1637-1645.

August, P., & Sibai, B. M. (2017). Preeclampsia: Clinical features and diagnosis. Post TW, UpToDate. Waltham, MA: UpToDate.

Bartal, M. F., & Sibai, B. M. (2020). Preeclampsia. Protocols for High‐Risk Pregnancies: An Evidence‐Based Approach, 517-528.

Bourassa, M. W., Abrams, S. A., Belizán, J. M., Boy, E., Cormick, G., Quijano, C. D., ... & Weaver, C. M. (2022). Interventions to improve calcium intake through foods in populations with low intake. Annals of the New York Academy of Sciences, 1511(1), 40-58. https://onlinelibrary.wiley.com/doi/full/10.1111/nyas.14743

Cao, R., Xie, J., & Zhang, L. (2022). Abnormal methylation caused by folic acid deficiency in neural tube defects. Open Life Sciences, 17(1), 1679-1688.

Chen, S., Li, N., Mei, Z., Ye, R., Li, Z., Liu, J., & Serdula, M. K. (2019). Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial. Clinical nutrition, 38(1), 146-151.

Colapinto, C. K., O’Connor, D. L., & Tremblay, M. S. (2011). Folate status of the population in the Canadian Health Measures Survey. Cmaj, 183(2), E100-E106. https://www.cmaj.ca/content/183/2/E100

Corsi, D. J., Gaudet, L. M., El-Chaar, D., White, R. R., Rybak, N., Harvey, A., ... & Walker, M. (2022). Effect of high-dose folic acid supplementation on the prevention of preeclampsia in twin pregnancy. The Journal of Maternal-Fetal & Neonatal Medicine, 35(3), 503-508. https://pubmed.ncbi.nlm.nih.gov/32067533/

De Ocampo, M. P., Araneta, M. R. G., Macera, C. A., Alcaraz, J. E., Moore, T. R., & Chambers, C. D. (2018). Folic acid supplement use and the risk of gestational hypertension and preeclampsia. Women and Birth, 31(2), e77-e83.

De Steur, H., Gellynck, X., Storozhenko, S., Liqun, G., Lambert, W., Van Der Straeten, D., & Viaene, J. (2010). Health impact in China of folate-biofortified rice. Nature Biotechnology, 28(6), 554-556.

Center for Disease Control and Prevention (CDC). (2024). About folic acid. Available from https://www.cdc.gov/folic-acid/about/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/folicacid/about.html

Cormick, G., Betrán, A. P., Metz, F., Palacios, C., Beltrán-Velazquez, F., Garcia-Casal, M. D. L. N., ... & Belizán, J. M. (2020). Regulatory and policy-related aspects of calcium fortification of foods. Implications for implementing national strategies of calcium fortification. Nutrients, 12(4), 1022.

Greenberg, J. A., Bell, S. J., Guan, Y., & Yu, Y. H. (2011). Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Reviews in obstetrics and gynecology, 4(2), 52.

Hofmeyr, G. J., Lawrie, T. A., Atallah, Á. N., & Torloni, M. R. (2018). Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane database of systematic reviews, (10).

Ledet III, L. F., Plaisance, C. J., Daniel, C. P., Wagner, M. J., Alvarez, I., Burroughs, C. R., ... & Varrassi, G. (2024). Spina Bifida Prevention: A Narrative Review of Folic Acid Supplements for Childbearing Age Women. Cureus, 16(1).

Kaldygulova, L., Ukybassova, T., Aimagambetova, G., Gaiday, A., & Tussupkaliyev, A. (2023). Biological role of folic acid in pregnancy and possible therapeutic application for the prevention of preeclampsia. Biomedicines, 11(2), 272.

Khalid, S. I., Thomson, K., Hunter, B. M., Garcia, R. M., Bowman, R., & Lam, S. (2023). The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects. Child's Nervous System, 39(7), 1813-1819.

Khan, B., Allah Yar, R., Khakwani, A. K., Karim, S., & Arslan Ali, H. (2022). Preeclampsia Incidence and its maternal and neonatal outcomes with Associated Risk factors. Cureus, 14: 11e31143.

Liu, Y., Li, N., Mei, Z., Li, Z., Ye, R., Zhang, L., ... & Serdula, M. K. (2021). Effects of prenatal micronutrients supplementation timing on pregnancy‐induced hypertension: Secondary analysis of a double‐blind randomized controlled trial. Maternal & Child Nutrition, 17(3), e13157.

Menezo, Y., Elder, K., Clement, A., & Clement, P. (2022). Folic acid, folinic acid, 5 methyl tetrahydrofolate supplementation for mutations that affect epigenesis through the folate and one-carbon cycles. Biomolecules, 12(2), 197.

Merrell, B. J., & McMurry, J. P. (2023). Folic acid. Encycl Toxicol Fourth Ed Vol 1-9. https://www.ncbi.nlm.nih.gov/books/NBK554487/

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., ... & Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. bmj, 372.

Sher, N., Mubaraki, M. A., Zafar, H., Nazli, R., Zafar, M., Fatima, S., & Fozia, F. (2022). Effect of lipid-based multiple micronutrients supplementation in underweight primigravida pre-eclamptic women on maternal and pregnancy outcomes: randomized clinical trial. Medicina, 58(12), 1772.

Tariq, K., Fatima, S., Nazli, R., Habib, S. H., & Shah, M. (2021). Impact of Lipid-Based Nutritional Supplementation in Primi-Gravidas and Its Effect on Maternal, Birth and Infant Outcomes: a randomized controlled trial. Khyber Medical University Journal, 13(4), 187-92.

Tyas, B. D., Lestari, P., & Akbar, M. I. A. (2019). Maternal perinatal outcomes related to advanced maternal age in preeclampsia pregnant women. Journal of family & reproductive health, 13(4), 191.

Wen, S. W., White, R. R., Rybak, N., Gaudet, L. M., Robson, S., Hague, W., ... & Walker, M. C. (2018). Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial. bmj, 362. https://pubmed.ncbi.nlm.nih.gov/30209050/

Willemse, J. P., Meertens, L. J., Scheepers, H. C., Achten, N. M., Eussen, S. J., van Dongen, M. C., & Smits, L. J. (2020). Calcium intake from diet and supplement use during early pregnancy: The Expect study I. European journal of nutrition, 59, 167-174.

World Health Organization (WHO. (2020). Calcium supplementation before pregnancy for the prevention of pre-eclampsia and its complications. WHO, Geneva, 1-38. https://apps.who.int/iris/bitstream/handle/10665/331787/9789240003118-eng.pdf?ua=1

Yu, E., & Sharma, S. (2018). Physiology, calcium. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482128/

Zheng, L., Huang, J., Kong, H., Wang, F., Su, Y., & Xin, H. (2020). The effect of folic acid throughout pregnancy among pregnant women at high risk of pre-eclampsia: A randomized clinical trial. Pregnancy hypertension, 19, 253-258.