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Chulalongkorn Medical Journal

Abstract

Background: Vitamin D, a fat-soluble prohormone, is essential for skeletal health and plays a key role in immune regulation. Deficiency is common among pregnant and lactating women, raising concerns as fetal and neonatal vitamin D status relies entirely on maternal stores. Insufficiency during these periods is linked to preterm birth, low birth weight, and immune-mediated disorders. This review examines the effects of maternal vitamin D supplementation on the immune development of offspring.

Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251117397). Experimental rodent studies published between 2019 and 2022 that investigated maternal vitamin D supplementation during pregnancy and/or lactation were included. Databases searched included PubMed, ScienceDirect, and EBSCOhost. Immunomodulatory outcomes in offspring were synthesized narratively.

Results: Four eligible studies consistently demonstrated that maternal vitamin D supplementation enhanced Th1 responses, suppressed Th2 and Th17 subsets, supported regulatory T cell function, and rebalanced cytokine profiles by reducing pro-inflammatory mediators (IL-6, IL-17, IL-23) and increasing anti-inflammatory cytokines (IL-10, TGF-β). At the molecular level, supplementation increased VDR and FOXP3 expression and decreased IFN-γ promoter methylation, suggesting epigenetic reprogramming.

Discussion: Maternal vitamin D appears to be a key determinant of early-life immune programming, potentially lowering risks of allergic, autoimmune, and chronic inflammatory conditions. While current evidence is limited to rodent models, maternal supplementation may offer a cost-effective strategy to enhance offspring immune resilience. Human studies with standardized protocols, detailed immune profiling, and long-term follow-up are warranted.

DOI

10.56808/2673-060X.5736

First Page

Type of article: Review Article Title of the article: Effects of Prenatal Vitamin D Supplementation on Offspring Immune Development: A Systematic Review Running Title: Maternal Vitamin D and Immune Development in Offspring Authors Kurnia Maidarmi Handayani1, Ghaniyyatul Khudri2, Laura Zeffira3 and Widia Sari4* 1Department of Biochemistry and Nutrition, Faculty of Medicine, Universitas Baiturrahmah, Padang, Indonesia 2Department of Histology and Immunology, Faculty of Medicine, Universitas Baiturrahmah, Padang, Indonesia 3Department of Pediatrics, Faculty of Medicine, Universitas Baiturrahmah, Padang, Indonesia 4Department of Anatomy, Physiology, and Radiology, Faculty of Medicine, Universitas Baiturrahmah, Padang, Indonesia *Corresponding Author: Name: Widia Sari, MD. Address: Faculty of Medicine, Universitas Baiturrahmah, ByPass Raya Street, KM. 15, Padang, 25176, Indonesia E-mail address: widia_sari@fk.unbrah.ac.id

Last Page

1. Chien M-C, Huang C-Y, Wang J-H, Shih C-L, Wu P. Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses. Nutr Diabetes. 2024; 14(1):35. 2. Ueda K, Chin SS, Sato N, Nishikawa M, Yasuda K, Miyasaka N, et al. Prenatal vitamin D deficiency exposure leads to long-term changes in immune cell proportions. Sci Rep. 2024; 14(1):19899. 3. Cyprian F, Lefkou E, Varoudi K, Girardi G. Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond. Front Immunol. 2019; 10. 4. Litonjua AA, Carey VJ, Laranjo N, Harshfield BJ, McElrath TF, O’Connor GT, et al. Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years. JAMA. 2016; 315(4):362. 5. Wolsk HM, Chawes BL, Litonjua AA, Hollis BW, Waage J, Stokholm J, et al. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PLoS One. 2017; 12(10):e0186657. 6. Durá-Travé T, Gallinas-Victoriano F. Pregnancy, Breastfeeding, and Vitamin D. Int J Mol Sci. 2023; 24(15):11881. 7. Zhu B, Yang J, Fan R, Song H, Zhong L, Zeng T, et al. Maternal vitamin D regulates the metabolic rearrangement of offspring CD4+ T cells in response to intestinal inflammation. Cell Rep. 2025; 44(6):115857. 8. Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014; 14(1):579. 9. Zhang L, Ni H, Zhou Z, Yuan X, Xia J, Jiang B, et al. 1α,25-Dihydroxyvitamin D3 Supplementation during Pregnancy Is Associated with Allergic Rhinitis in the Offspring by Modulating Immunity. J Immunol Res. 2021; 2021:1–12. 10. Jiao X, Wang L, Wei Z, Liu B, Liu X, Yu X. Vitamin D deficiency during pregnancy affects the function of Th1/Th2 cells and methylation of IFN-γ gene in offspring rats. Immunol Lett. 2019; 212:98–105. 11. Zhang Q, Zhao J, Ni M, Shen Q, Zhou W, Liu Z. Vitamin D3 reverses the transcriptional profile of offspring CD4+ T lymphocytes exposed to intrauterine inflammation. J Steroid Biochem Mol Biol. 2022; 221:106120. 12. Wang G, Li Y, Li Y, Zhang J, Zhou C, Wu C, et al. Maternal vitamin D supplementation inhibits bisphenol A-induced proliferation of Th17 cells in adult offspring. Food and Chemical Toxicology. 2020; 144:111604. 13. Chen WJ, Hou XJ, Yang SF, Yin XH, Ren L. Effect of vitamin D supplementation during pregnancy on the Th1/Th2 cell balance of rat offspring. Pharmazie. Govi-Verlag Pharmazeutischer Verlag GmbH; 2014; 69(5):385–90. 14. Bivona G, Agnello L, Ciaccio M. The immunological implication of the new vitamin D metabolism. Central European Journal of Immunology. 2018; 43(3):331–4. 15. Li Q, Xu X, Liu Y, Yin S, Hu Q, Ji Q, et al. The effects of prenatal vitamin D supplementation on respiratory and allergy-related outcomes in children: A systematic review and meta-analysis of randomized controlled trials. World Allergy Organization Journal. 2025; 18(7):101075. 16. Huang F, Ju Y, Wang H, Li Y. Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflammation. Allergy, Asthma & Clinical Immunology. 2020; 16(1):89. 17. Zhang Q, Yang D, Shen Q, Li W, Li R, Tang Y, et al. Correlation of Maternal Vitamin D Status in Early Pregnancy and Vitamin D Supplementation during Pregnancy with Atopic Dermatitis in Infants: A Prospective Birth Cohort Study. Nutrients. 2024; 16(13):2168. 18. World Health Organization. WHO antenatal care recommendations for a positive pregnancy experience Nutritional interventions update: Vitamin D supplements during pregnancy. 2020.

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