Vitamin D and Pregnancy: Research Review

Most of us are already familiar with vitamin D… it’s the sunshine vitamin. Our bodies synthesize it when we show a little skin and spend some time under the sun. However, for good reasons, many of us suffer from low vitamin D levels.

Vitamin D is best known for its role in bone health – which is why it’s often added to milk and other calcium products. However, decades of research have linked it to multiple other health roles. Importantly, vitamin D modulates the immune system, which could be the crucial link between low vitamin D levels and reproductive complications.

Physiology

Vitamin D is a fat-soluble vitamin belonging to the steroid hormone family. Two main forms are essentials:

• Vitamin D2 (ergocalciferol) that you can get through your diet.
• Vitamin D3 (cholecalciferol) that you synthetize after sun exposure and represent 95% of your vitamin D production, once metabolized to generate calcitriol (the active form of Vitamin D)³.

By binding to its receptor (VDR), calcitriol (active form of vitamin D) regulates over 900 genes in human including several actions in reproductive tissues.

Vitamin D and its receptor are present in the ovaries⁴ where they stimulate the production of the steroid hormones estrogen and progesterone⁵. The endometrium (uterus) itself can synthesize the active form of Vitamin D⁶ and express the vitamin D receptor VDR as well⁴.

Published clinical data

Low levels of vitamin D are common in pregnant women and has been shown in several epidemiological studies worldwide. Vitamin D deficiency is associated with an increased risk of infection⁷, bacterial vaginosis⁸, pre-eclampsia⁹ and low serum vitamin D levels in the newborn¹⁰.

In a published study¹¹, results showed that sufficient and adequate Vitamin D levels prior to conception may reduce the risk for another miscarriage in patients having suffered previous losses.

Vitamin D plays an important role in the modulation of the immune function¹² and oxidative stress¹³ with dramatic impact on fertility ranging from poor oocyte quality, miscarriage to pregnancy complication including pre-eclampsia, preterm labor and stillbirth^{12, 14}. The activation of the vitamin D pathway has multiple beneficial effects on the immune function leading to less inflammation^15-18.

About Pregmune: We’re an innovative reproductive health technology company, built on a solid foundation of data gained from decades of experience and thousands of successful pregnancies. Our team of fertility specialists and scientists are using artificial intelligence to decipher the complexity of the immune system and help patients grow the families of their dreams.

Our first product, IRMA, provides patients and their doctors with a personalized report and evidence-based treatment plan that addresses immunological sources of unexplained infertility, recurrent pregnancy loss, and recurrent implantation failure.

References

1. IOM (Institute of Medicine). 2010. Dietary reference intakes for calcium and D. Washington DC: The National Academies Press.
2. Holick MF, Binkley NC, Bischoff−Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. JCEM. 2011 Jul; 96(7):1911−30.
3. Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. Review.
4. Agic A, Xu H, Altgassen C, Noack F, Wolfler MM, Diedrich K, Friedrich M, Taylor RN & Hornung D. Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1a-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reproductive Sciences 2007 14 486–497.
5. Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L & Seto-Young D. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Hormone and Metabolic Research 2010 42 754–757.
6. Vigano` P, Lattuada D, Mangioni S, Ermellino L, Vignali M, Caporizzo E, Panina-Bordignon P, Besozzi M & Di Blasio AM. Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. Journal of Molecular Endocrinology 2006 36 415–424.
7. Gunville CF, Mourani PM, Ginde AA. The role of vitamin D in prevention and treatment of infection. Inflamm Allergy Drug Targets. 2013 Aug;12(4):239-45. Review.
8. Taheri M, Baheiraei A, Foroushani AR, Nikmanesh B, Modarres M. Treatment of vitamin D deficiency is an effective method in the elimination of asymptomatic bacterial vaginosis: A placebo-controlled randomized clinical trial. Indian J Med Res. 2015 Jun;141(6):799-806
9. Sablok A, Batra A, Thariani K, Batra A, Bharti R, Aggarwal AR, Kabi BC, Chellani H. Supplementation of vitamin D in pregnancy and its correlation with feto-maternal outcome. Clin Endocrinol (Oxf). 2015 Oct;83(4):536-41.
10. Rodda CP, Benson JE, Vincent AJ, Whitehead CL, Polykov A, Vollenhoven B. Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open label randomized controlled trial. Clin Endocrinol (Oxf). 2015 Sep;83(3):363-8.
11. Mumford SL, Garbose RA, Kim K, Kissell K, Kuhr DL, Omosigho UR, Perkins NJ, Galai N, Silver RM, Sjaarda LA, Plowden TC, Schisterman EF. Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. Lancet Diabetes Endocrinol. 2018 Sep;6(9):725-732.
12. Ji JL, Muyayalo KP, Zhang YH, Hu XH, Liao AH. Immunological function of vitamin D during human pregnancy. Am J Reprod Immunol. 2017 Aug;78(2).
13. Farhangi MA,Mesgari-Abbasi M, Hajiluian G, Nameni G, Shahabi P. Adipose tissue inflammation and oxidative stress: the ameliorative effects of vitamin D. Inflammation. 2017;40(5):1688-1697.
14. Pourghassem Gargari B, Pourteymour Fard Tabrizi F, Sadien B, Asghari Jafarabadi M, Farzadi L. Vitamin D Status Is Related to Oxidative Stress but Not High-Sensitive C-Reactive Protein in Women with Pre-Eclampsia. Gynecol Obstet Invest. 2016;81(4):308-14.
15. Adorini L, Amuchastegui S, Daniel KC. Prevention of chronic allograft rejection by Vitamin D receptor agonists. Immunol Lett. 2005 Aug 15;100(1):34-41. Review.
16. Cippitelli M, Santoni A. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol. 1998 Oct;28(10):3017-30.
17. Helming L, Böse J, Ehrchen J, Schiebe S, Frahm T, Geffers R, Probst-Kepper M, Balling R, Lengeling A. 1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation. Blood. 2005 Dec 15;106(13):4351-8.
18. Giarratana N, Penna G, Amuchastegui S, Mariani R, Daniel KC, Adorini L. A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development. J Immunol. 2004 Aug 15;173(4):2280-7.