Daily cholecalciferol supplementation during pregnancy alters markers of regulatory immunity, inflammation, and clinical outcomes in a randomized controlled trial

Journal of Nutrition

Volumn 146, Issue 11, 2016, Pages 2388-2397

  Zerofsky, Melissa S ^a,b   Jacoby, Bryon N ^a,c   Pedersen, Theresa L ^b   Stephensen, Charles B ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b USDAWestern Human Nutrition Research Center   (United States)

^c Shenandoah Valley Maternal Fetal Medicine   (United States)

Author keywords

Clinical trial; Cytokines; Pregnancy; T cell; Vitamin D

Indexed keywords

CD4 ANTIGEN; COLECALCIFEROL; INTERLEUKIN 10; BIOLOGICAL MARKER; CYTOKINE; TOLL LIKE RECEPTOR;

ARTICLE; BIRTH WEIGHT; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DIASTOLIC BLOOD PRESSURE; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; HUMAN; IMMUNITY; INFLAMMATION; MEDICATION COMPLIANCE; OUTCOME ASSESSMENT; PREGNANCY; PREGNANCY OUTCOME; RANDOMIZED CONTROLLED TRIAL; VITAMIN SUPPLEMENTATION; ADULT; DIETARY SUPPLEMENT; DOSE RESPONSE; DRUG ADMINISTRATION; GENETICS; METABOLISM;

ADULT; BIOMARKERS; CD4-POSITIVE T-LYMPHOCYTES; CHOLECALCIFEROL; CYTOKINES; DIETARY SUPPLEMENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; INFLAMMATION; INTERLEUKIN-10; PREGNANCY; TOLL-LIKE RECEPTORS;

EID: 84995529447     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.116.231480     Document Type: Article

References (71)

1. Ginde AA, Sullivan AF, Mansbach JM, Camargo CA. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol 2010;202:436.e1-8.
2. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006;116:2062-72.
3. Shand AW, Nassar N, Dadelszen Von P, Innis SM, Green TJ. Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for pre-eclampsia. BJOG 2010;117:1593-8.
4. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 2007;92:3517-22.
5. Baker AM, Haeri S, Camargo CA, Jr., Espinola JA, Stuebe AM. A nested case-control study of midgestation vitamin D deficiency and risk of severe preeclampsia. J Clin Endocrinol Metab 2010;95:5105-9.
6. Robinson CJ, Alanis MC, Wagner CL, Hollis BW, Johnson DD. Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. Am J Obstet Gynecol 2010;203:366.e1-6.
7. Haugen M, Brantsaeter AL, Trogstad L, Alexander J, Roth C, Magnus P, Meltzer HM. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology 2009;20:720-6.
8. Hyppönen E. Preventing vitamin D deficiency in pregnancy-importance for the mother and child. Ann Nutr Metab 2011;59:28-31.
9. Wagner CL, McNeil RB, Johnson DD, Hulsey TC, Ebeling M, Robinson C, Hamilton SA, Hollis BW. Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol 2013;136:313-20.
10. Davis LM, Chang S-C, Mancini J, Nathanson MS, Witter FR, O'Brien KO, Vitamin D. Insufficiency is prevalent among pregnant African American adolescents. J Pediatr Adolesc Gynecol 2010;23:45-52.
11. Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr 2009;139:1157-61.
12. Hensel KJ, Randis TM, Gelber SE, Ratner AJ. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol 2011;204:41.e1-9.
13. Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R. Maternal vitamin D, folate, and polyunsaturated fatty acid status and bacterial vaginosis during pregnancy. Infect Dis Obstet Gynecol 2011;2011:216217.
14. Zhang C, Qiu C, Hu FB, David RM, van Dam RM, Bralley A, Williams MA. Maternal plasma 25-hydroxyvitamin D concentrations and the risk for gestational diabetes mellitus. PLoS One 2008;3:e3753.
15. Parlea L, Bromberg IL, Feig DS, Vieth R, Merman E, Lipscombe LL. Association between serum 25-hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitus. Diabet Med 2012;29: e25-32.
16. Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei A-R, Larijani B. Correlation between vitamin D3 deficiency and insulin resistance in pregnancy. Diabetes Metab Res Rev 2008;24:27-32.
17. Boggess KA, Espinola JA,Moss K, Beck J, Offenbacher S, Camargo CA. Vitamin D status and periodontal disease among pregnant women. J Periodontol 2011;82:195-200.
18. Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, Marazita ML, Simhan HN. Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr 2010;140:999-1006.
19. Camargo CA, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, Kleinman K, Gillman MW. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007;85:788-95.
20. Devereux G, Litonjua AA, Turner SW, Craig LCA, McNeill G, Martindale S, Helms PJ, Seaton A, Weiss ST. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr 2007;85:853-9.
21. Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippilä C, Ahonen S, Nevalainen J, Veijola R, Pekkanen J, Ilonen J, Simell O, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy 2009;39:875-82.
22. Camargo CA, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, Town GI, Pattemore PK, Espinola JA, Crane J, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics 2011;127:e180-7.
23. Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LC. Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes 2012;61:175-8.
24. Racicot K, Kwon J-Y, Aldo P, Silasi M, Mor G. Understanding the complexity of the immune system during pregnancy. Am J Reprod Immunol 2014;72:107-16.
25. Alijotas-Reig J, Llurba E, Gris JM. Potentiating maternal immune tolerance in pregnancy: a new challenging role for regulatory T cells. Placenta 2014;35:241-8.
26. Tamblyn JA, Hewison M, Wagner CL, Bulmer JN, Kilby MD. Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol 2015;224:R107-21.
27. Chambers ES, Hawrylowicz CM. The impact of vitamin D on regulatory T cells. Curr Allergy Asthma Rep 2011;11:29-36.
28. Smolders J, Peelen E, Thewissen M, Cohen Tervaert JW, Menheere P, Hupperts R, Damoiseaux J. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 2010;5:e15235.
29. Urry Z, Chambers ES, Xystrakis E, Dimeloe S, Richards DF, Gabry'sová L, Christensen J, Gupta A, Saglani S, Bush A, et al. The role of 1a,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells. Eur J Immunol 2012;42:2697-708.
30. Bakdash G, van Capel TMM, Mason LMK, Kapsenberg ML, de Jong EC. Vitamin D3 metabolite calcidiol primes human dendritic cells to promote the development of immunomodulatory IL-10-producing T cells. Vaccine 2014;32:6294-302.
31. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A. 1a,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001;167:4974-80.
32. Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol 2007;179:2060-3.
33. Bodnar LM, Klebanoff MA, Gernand AD, Platt RW, Parks WT, Catov JM, Simhan HN. Maternal vitamin D status and spontaneous preterm birth by placental histology in the US Collaborative Perinatal Project. Am J Epidemiol 2014;179:168-76.
34. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington (DC): National Academy Press; 2011.
35. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.
36. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84(1):18-28. Errata in: Am J Clin Nutr 2006;84(5):1253 and Am J Clin Nutr 2006;86(3):809.
37. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011;26:2341-57.
38. Dawodu A, Saadi HF, Bekdache G, Javed Y, Altaye M, Hollis BW. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab 2013;98:2337-46.
39. Ng K, Scott JB, Drake BF, Chan AT,Hollis BW, Chandler PD, BennettGG, Giovannucci EL, Gonzalez-Suarez E,Meyerhardt JA, et al. Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial. Am J Clin Nutr 2014;99:587-98.
40. Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser JR, Woodhouse LR, Stephensen CB. Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. J Nutr 2010;140:542-50.
41. Schleithoff SS, Zittermann A, Tenderich G, Berthold H, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006;83:754-9.
42. Bock G, Prietl B, Mader JK, Höller E, Wolf M, Pilz S, Graninger WB, Obermayer-Pietsch BM, Pieber TR. The effect of vitamin D supplementation on peripheral regulatory T cells and b cell function in healthy humans: a randomized controlled trial. Diabetes Metab Res Rev 2011;27:942-5.
43. Pfeifer M, Begerow B, Minne H, Nachtigall D, Hansen C. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab 2001;86:1633-7.
44. Hollis BW, Wagner CL. Vitamin D and pregnancy: skeletal effects, nonskeletal effects, and birth outcomes. Calcif Tissue Int 2013;92:128-39.
45. Kumar R, Cohen WR, Silva P, Epstein FH. Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest 1979;63:342-4.
46. Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest 1984;74:1966-71.
47. Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and placental-decidual function. J Soc Gynecol Investig 2004;11:263-71.
48. Verhaeghe J, Bouillon R. Calciotropic hormones during reproduction. J Steroid Biochem Mol Biol 1992;41:469-77.
49. Steinborn A, Schmitt E, Kisielewicz A, Rechenberg S, Seissler N, Mahnke K, Schaier M, Zeier M, Sohn C. Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs. Clin Exp Immunol 2012;167:84-98.
50. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004;5:266-71.
51. Zenclussen AC, Gerlof K, Zenclussen ML, Sollwedel A, Bertoja AZ, Ritter T, Kotsch K, Leber J, Volk H-D. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol 2005;166:811-22.
52. Vijayendra Chary A, Hemalatha R, Seshacharyulu M, Vasudeva Murali M, Jayaprakash D, Dinesh Kumar B. Reprint of ''Vitamin D deficiency in pregnant women impairs regulatory T cell function.'' J Steroid Biochem Mol Biol 2015;148:194-201.
53. Prietl B, Treiber G,Mader JK, Hoeller E,Wolf M, Pilz S, Graninger WB, Obermayer-Pietsch BM, Pieber TR. High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutr 2014;53:751-9.
54. Smolders J, Damoiseaux J, Menheere P, Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 2008;194:7-17.
55. Wei SQ, Audibert F, Hidiroglou N, Sarafin K, Julien P, Wu Y, Luo ZC, Fraser WD. Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia. BJOG 2012;119:832-9.
56. Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR. 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 2011;57:63-9.
57. Chitalia N, Ismail T, Tooth L, Boa F, Hampson G, Goldsmith D, Kaski JC, Banerjee D. Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients. PLoS One 2014;9:e91363.
58. Wei S-Q, Audibert F, Luo Z-C, Nuyt AM, Masse B, Julien P, Fraser WD. Maternal plasma 25-hydroxyvitamin D levels, angiogenic factors, and preeclampsia. Am J Obstet Gynecol 2013;208:390.e1-6.
59. Jones AP, D'Vaz N, Meldrum S, Palmer DJ, Zhang G, Prescott SL. 25-Hydroxyvitamin D3 status is associated with developing adaptive and innate immune responses in the first 6 months of life. Clin Exp Allergy 2015;45:220-31.
60. Khoo AL, Chai LYA, Koenen HJPM, Sweep FCGJ, Joosten I, Netea MG, van der Ven AJAM. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol 2011;164:72-9.
61. Li YC, Qiao G, Uskokovic M, XiangW, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol 2004;89-90:387-92.
62. Marya RK, Rathee S, Manrow M. Effect of calcium and vitamin D supplementation on toxaemia of pregnancy. Gynecol Obstet Invest 1987;24:38-42.
63. Mannion CA, Gray-Donald K, Koski KG. Association of low intake of milk and vitamin D during pregnancy with decreased birth weight. CMAJ 2006;174:1273-7.
64. Scholl TO, Chen X. Vitamin D intake during pregnancy: association with maternal characteristics and infant birth weight. Early Hum Dev 2009;85:231-4.
65. Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab 2006;91:906-12.
66. Dror DK, Allen LH. Vitamin D inadequacy in pregnancy: biology, outcomes, and interventions. Nutr Rev 2010;68:465-77.
67. Sabour H, Hossein-Nezhad A, Maghbooli Z, Madani F, Mir E, Larijani B. Relationship between pregnancy outcomes and maternal vitamin D and calcium intake: a cross-sectional study. Gynecol Endocrinol 2006;22:585-9.
68. Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN, Godfrey KM, Cooper C. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008;62:68-77.
69. Farrant HJW, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, Osmond C, Veena SR, Fall CHD. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J Clin Nutr 2008; 63:646-52.
70. Pérez-López FR, Pasupuleti V, Mezones-Holguin E, Benites-Zapata VA, Thota P, Deshpande A, Hernandez AV. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2015;103:1278-88.e4.
71. Moon RJ, Harvey NC, Cooper C. Endocrinology in pregnancy: influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton. Eur J Endocrinol 2015;173:R69-83.