Comparison of Vitamin D Status Between Infants With Dilated Cardiomyopathy and Infants With Other Congenital Heart Diseases

Document Type : Original Article


1 Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

2 Student Research Committee, Department of Clinical Nutrition and Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Medicine and Life Sciences, Kings College London, University of London, Strand, London, WC2R 2LS.


Background: Vitamin D plays an essential role in calcium homeostasis and cardiac muscle function, hence the significance of the screening, diagnosing, preventing, and treating of vitamin D deficiency (VDD). In children susceptible to VDD, cardiomyopathy is a likely occurrence. We sought to compare vitamin D status between children with dilated cardiomyopathy (DCM) and children with other congenital heart diseases.
Methods: This observational case-control study, conducted from 2018 through 2019 in Rajaie Cardiovascular Medical and Research Center, compared vitamin D status between a case group, consisting of 33 infants with DCM, and a control group, composed of 35 infants with other congenital heart diseases. The serum levels of iron, magnesium, calcium, albumin, parathyroid hormone, and 25(OH)D3 were measured in all the children.
Results: The study population consisted of 68 infants (31 males and 37 females) at a mean age of 64.96±51 days. The DCM group presented with a significantly higher incidence of VDD (27.3%) than the control group (8.6%). Multivariable-adjusted analysis for DCM based on the tertiles of vitamin D levels revealed an odds ratio of 0.25 (95% CI, 0.06 to 1.01) for tertile 3 (>24 nmol/L) compared with an odds ratio of 0.89 (95% CI, 0.24 to 3.30) for tertile 2 (16–24 nmol/L) and tertile 1 (<16 nmol/L) designated as the reference (P=0.05), indicating near statistical significance.
Conclusions: In assessing a child with newly diagnosed DCM or other congenital heart diseases, VDD and electrolyte imbalances should be promptly screened to avert the precipitating decompensation of the cardiovascular function. (Iranian Heart Journal 2022; 23(1): 160-171)



    1. Richardson, P., et al., Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation, 1996. 93(5): p. 841-2.
    2. Kirk, R., et al., Outcome of pediatric patients with dilated cardiomyopathy listed for transplant: a multi-institutional study. The Journal of Heart and Lung Transplantation, 2009. 28(12): p. 1322-1328.
    3. Towbin, J.A., et al., Incidence, causes, and outcomes of dilated cardiomyopathy in children. Jama, 2006. 296(15): p. 1867-76.
    4. Tsirka, A.E., et al., Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation. J Am Coll Cardiol, 2004. 44(2): p. 391-7.
    5. Lipshultz, S.E., et al., The Incidence of Pediatric Cardiomyopathy in Two Regions of the United States. New England Journal of Medicine, 2003. 348(17): p. 1647-1655.
    6. Nugent, A.W., et al., The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med, 2003. 348(17): p. 1639-46.
    7. Alvarez Jorge, A., et al., Competing Risks for Death and Cardiac Transplantation in Children With Dilated Cardiomyopathy. Circulation, 2011. 124(7): p. 814-823.
    8. Wilkinson, J.D., et al., The pediatric cardiomyopathy registry and heart failure: key results from the first 15 years. Heart failure clinics, 2010. 6(4): p. 401-vii.
    9. Carvajal, K. and R. Moreno-Sánchez, Heart Metabolic Disturbances in Cardiovascular Diseases. Archives of Medical Research, 2003. 34(2): p. 89-99.
    10. Holick, M.F., Vitamin D deficiency. N Engl J Med, 2007. 357(3): p. 266-81.
    11. Anderson, J.L., et al., Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. The American journal of cardiology, 2010. 106(7): p. 963-968.
    12. Kendrick, J., et al., 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis, 2009. 205(1): p. 255-260.
    13. Skaaby, T., et al., Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population. Cardiology, 2012. 123(1): p. 62-70.
    14. Wang, L., et al., Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circulation: Cardiovascular Quality and Outcomes, 2012. 5(6): p. 819-829.
    15. Weyland, P.G., W.B. Grant, and J. Howie-Esquivel, Does sufficient evidence exist to support a causal association between vitamin D status and cardiovascular disease risk? An assessment using Hill’s criteria for causality. Nutrients, 2014. 6(9): p. 3403-3430.
    16. Censani, M., et al., Vitamin D deficiency associated with markers of cardiovascular disease in children with obesity. Global pediatric health, 2018. 5: p. 2333794X17751773.
    17. Colak, R., et al., Metabolic disturbances and cardiovascular risk factors in obese children with vitamin D deficiency. Archives de Pédiatrie, 2020.
    18. Earthman, C.P., et al., The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. International journal of obesity, 2012. 36(3): p. 387-396.
    19. Lee, M., et al., Inverse associations between cardiometabolic risk factors and 25‐hydroxyvitamin D in obese American children and adolescents. American Journal of Human Biology, 2016. 28(5): p. 736-742.
    20. Petersen, R.A., et al., Vitamin D status is associated with cardiometabolic markers in 8–11-year-old children, independently of body fat and physical activity. British Journal of Nutrition, 2015. 114(10): p. 1647-1655.
    21. Sauder, K.A., et al., Cord Blood Vitamin D Levels and Early Childhood Blood Pressure: The Healthy Start Study. Journal of the American Heart Association, 2019. 8(9): p. e011485.
    22. Theodoratou, E., et al., Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. Bmj, 2014. 348: p. g2035.
    23. Wang, G., et al., Vitamin D Trajectories From Birth to Early Childhood and Elevated Systolic Blood Pressure During Childhood and Adolescence. Hypertension, 2019. 74(2): p. 421-430.
    24. Delvin, E.E., et al., Vitamin D Status Is Modestly Associated with Glycemia and Indicators of Lipid Metabolism in French-Canadian Children and Adolescents. The Journal of Nutrition, 2010. 140(5): p. 987-991.
    25. Salo, A. and J.V. Logomarsino, Relationship of vitamin D status and cardiometabolic risk factors in children and adolescents. Pediatr Endocrinol Rev, 2011. 9(1): p. 456-62.
    26. Williams, D.M., et al., Associations of 25-Hydroxyvitamin D2 and D3 with Cardiovascular Risk Factors in Childhood: Cross-Sectional Findings from the Avon Longitudinal Study of Parents and Children. The Journal of Clinical Endocrinology & Metabolism, 2012. 97(5): p. 1563-1571.
    27. Manson, J.E., et al., Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. New England Journal of Medicine, 2018. 380(1): p. 33-44.
    28. Ford, J.A., et al., Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. The American journal of clinical nutrition, 2014. 100(3): p. 746-755.
    29. Barbarawi, M., et al., Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis. JAMA Cardiol, 2019. 4(8): p. 765-776.
    30. Ferira, A.J., et al., Vitamin D supplementation does not impact insulin resistance in black and white children. The Journal of Clinical Endocrinology & Metabolism, 2016. 101(4): p. 1710-1718.
    31. Hauger, H., et al., Winter Cholecalciferol Supplementation at 55°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Children Aged 4–8 Years. The Journal of Nutrition, 2018. 148(8): p. 1261-1268.
    32. Magge, S.N., et al., Vitamin D3 supplementation in obese, African-American, vitamin D deficient adolescents. Journal of clinical & translational endocrinology, 2018. 12: p. 1-7.
    33. Shah, S., D.M. Wilson, and L.K. Bachrach, Large doses of vitamin D fail to increase 25-hydroxyvitamin D levels or to alter cardiovascular risk factors in obese adolescents: a pilot study. Journal of Adolescent Health, 2015. 57(1): p. 19-23.
    34. Smith, T.J., et al., Winter Cholecalciferol Supplementation at 51°N Has No Effect on Markers of Cardiometabolic Risk in Healthy Adolescents Aged 14–18 Years. The Journal of Nutrition, 2018. 148(8): p. 1269-1275.
    35. Varshney, S., et al., Effect of high-dose vitamin D supplementation on beta cell function in obese Asian-Indian children and adolescents: A randomized, double blind, active controlled study. Indian Journal of Endocrinology and Metabolism, 2019. 23(5): p. 545.
    36. Weishaar, R.E. and R.U. Simpson, Vitamin D3 and cardiovascular function in rats. The Journal of clinical investigation, 1987. 79(6): p. 1706-1712.
    37. Oconnell, T.D. and R.U. Simpson, 1, 25-Dihydroxyvitamin D3 regulation of myocardial growth and c-myc levels in the rat heart. Biochemical and biophysical research communications, 1995. 213(1): p. 59-65.
    38. Weishaar, R.E., et al., Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties. American Journal of Physiology-Endocrinology and Metabolism, 1990. 258(1): p. E134-E142.
    39. Li, Y.C., et al., 1, 25-Dihydroxyvitamin D 3 is a negative endocrine regulator of the renin-angiotensin system. The Journal of clinical investigation, 2002. 110(2): p. 229-238.
    40. Rahman, A., et al., Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. The Journal of steroid biochemistry and molecular biology, 2007. 103(3-5): p. 416-419.
    41. Weber, K.T., Fibrosis and hypertensive heart disease. Current opinion in cardiology, 2000. 15(4): p. 264-272.
    42. Xiang, W., et al., Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. American Journal of Physiology-Endocrinology and Metabolism, 2005. 288(1): p. E125-E132.
    43. Zhou, C., et al., Calcium-independent and 1, 25 (OH) 2D3-dependent regulation of the renin-angiotensin system in 1α-hydroxylase knockout mice. Kidney international, 2008. 74(2): p. 170-179.
    44. Gardner, D.G., S. Chen, and D.J. Glenn, Vitamin D and the heart. American journal of physiology. Regulatory, integrative and comparative physiology, 2013. 305(9): p. R969-R977.
    45. Norman, P.E. and J.T. Powell, Vitamin D and Cardiovascular Disease. Circulation Research, 2014. 114(2): p. 379-393.
    46. Tishkoff, D.X., et al., Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology, 2008. 149(2): p. 558-64.
    47. Somjen, D., et al., 25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation, 2005. 111(13): p. 1666-71.
    48. Merke, J., et al., Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest, 1989. 83(6): p. 1903-15.
    49. Chen, S., et al., Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results in Cardiac Hypertrophy. Circulation, 2011. 124(17): p. 1838-1847.
    50. Ameri, P., et al., Relationship between vitamin D status and left ventricular geometry in a healthy population: results from the Baltimore Longitudinal Study of Aging. Journal of Internal Medicine, 2013. 273(3): p. 253-262.
    51. Polat, V., et al., Low vitamin D status associated with dilated cardiomyopathy. International journal of clinical and experimental medicine, 2015. 8(1): p. 1356-1362.
    52. Witte, K.K., et al., Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. Journal of the American College of Cardiology, 2016. 67(22): p. 2593-2603.
    53. Prentice, A., Nutritional rickets around the world. J Steroid Biochem Mol Biol, 2013. 136: p. 201-6.
    54. Brunvand, L., et al., Congestive heart failure caused by vitamin D deficiency? Acta Pædiatrica, 1995. 84(1): p. 106-108.
    55. Cramm, K.J., R.A. Cattaneo, and R.D. Schremmer, An infant with tachypnea. Pediatric Emergency Care, 2006. 22(11): p. 728-731.
    56. Gillor, A., et al., Congestive heart failure in an infant due to vitamin D deficiency rickets. Monatsschrift fur Kinderheilkunde, 1989. 137(2): p. 108-110.
    57. Kim, B.G., et al., Dilated cardiomyopathy in a 2 month-old infant: A severe form of hypocalcemia with vitamin D deficient rickets. Korean Circulation Journal, 2010. 40(4): p. 201-203.
    58. Kumar, M., et al., Vitamin D deficiency presenting with cardiogenic shock in an infant. Annals of Pediatric Cardiology, 2011. 4(2): p. 207-209.
    59. Mustafa, A., J.L. Bigras, and B.W. McCrindle, Dilated cardiomyopathy as a first sign of nutritional vitamin D deficiency rickets in infancy. Canadian Journal of Cardiology, 1999. 15(6): p. 699-701.
    60. Olgun, H., N. Ceviz, and B. Özkan, A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Turkish Journal of Pediatrics, 2003. 45(2): p. 152-154.
    61. Price, D.I., et al., Hypocalcemic rickets: An unusual cause of dilated cardiomyopathy. Pediatric Cardiology, 2003. 24(5): p. 510-512.
    62. Verma, S., et al., Hypocalcemia nutritional rickets: A curable cause of dilated cardiomyopathy. Journal of Tropical Pediatrics, 2011. 57(2): p. 126-128.
    63. Yaseen, H., et al., Hypocalcemic heart failure in vitamin D deficient rickets. Pediatrie, 1993. 48(7-8): p. 547-549.
    64. Eren, E., et al., A treatable cause of cardiomyopathy: Vitamin D deficiency. Guncel Pediatri, 2015. 13(2): p. 143-146.
    65. Kosecik, M. and T. Ertas, Dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Pediatrics International, 2007. 49(3): p. 397-399.
    66. Amirlak, I., W. Al Dhaheri, and H. Narchi, Dilated cardiomyopathy secondary to nutritional rickets. Annals of Tropical Paediatrics, 2008. 28(3): p. 227-230.
    67. Brown, J., et al., Hypocalcemic rickets and dilated cardiomyopathy: Case reports and review of literature. Pediatric Cardiology, 2009. 30(6): p. 818-823.
    68. Carlton-Conway, D., et al., Vitamin D deficiency and cardiac failure in infancy. Journal of the Royal Society of Medicine, 2004. 97(5): p. 238-239.
    69. Yazici, M.U., et al., Reversible Dilated Cardiomyopathy Due to Combination of Vitamin D-Deficient Rickets and Primary Hypomagnesemia in an 11-Month-Old Infant. J Pediatr Intensive Care, 2018. 7(1): p. 46-48.
    70. Elidrissy, A.T.H., M. Munawarah, and K.M. Alharbi, Hypocalcemic rachitic cardiomyopathy in infants. Journal of the Saudi Heart Association, 2013. 25(1): p. 25-33.
    71. Gupta, P., et al., Hypocalcemic cardiomyopathy presenting as cardiogenic shock. Annals of Pediatric Cardiology, 2011. 4(2): p. 152-155.
    72. Maiya, S., et al., Hypocalcaemia and vitamin D deficiency: An important but preventable, cause of life-threatening infant heart failure. Heart, 2008. 94(5): p. 581-584.
    73. Glackin, S., et al., Dilated cardiomyopathy secondary to vitamin D deficiency and hypocalcaemia in the Irish paediatric population: A case report. Ir Med J, 2017. 110(3): p. 535.
    74. Hunter, L., R. Ferguson, and H. McDevitt, Vitamin D deficiency cardiomyopathy in Scotland: a retrospective review of the last decade. Arch Dis Child, 2020.
    75. Yilmaz, O., et al., Dilated cardiomyopathy secondary to rickets-related hypocalcaemia: eight case reports and a review of the literature. Cardiol Young, 2015. 25(2): p. 261-6.
    76. Högler, W., Complications of vitamin D deficiency from the foetus to the infant: One cause, one prevention, but who's responsibility? Best Practice and Research: Clinical Endocrinology and Metabolism, 2015. 29(3): p. 385-398.
    77. Tomar, M., S. Radhakrishnan, and S. Shrivastava, Myocardial dysfunction due to hypocalcemia. Indian Pediatrics, 2010. 47(9): p. 781-783.
    78. Uysal, S., A.G. Kalayci, and K. Baysal, Cardiac functions in children with vitamin D deficiency rickets. Pediatric Cardiology, 1999. 20(4): p. 283-286.
    79. Sanyal, D. and M. Raychaudhuri, Infants with dilated cardiomyopathy and hypocalcemia. Indian journal of endocrinology and metabolism, 2013. 17(Suppl 1): p. S221-S223.
    80. Noori, N.M., et al., 25-hydroxy Vitamin D Serum levels in Congenital Heart Disease (CHD) Children Compared to Controls. International Journal of Pediatrics, 2018. 6(8): p. 8129-8138.
    81. Jammal Addin, M.B., et al., Dilated cardiomyopathy in a national paediatric population. European Journal of Pediatrics, 2019. 178(8): p. 1229-1235.
    82. Peroni, D.G., et al., Vitamin D in pediatric health and disease. Pediatric Allergy and Immunology, 2020. 31(S24): p. 54-57.
    83. Andiran, N., N. Yordam, and A. Ozön, Risk factors for vitamin D deficiency in breast-fed newborns and their mothers. Nutrition, 2002. 18(1): p. 47-50.
    84. Ari, H., et al., A rare cause of reversible dilated cardiomyopathy: Hypocalcemia. Turk Kardiyoloji Dernegi Arsivi, 2009. 37(4): p. 266-268.
    85. Csanady, M., T. Forster, and J. Julesz, Reversible impairment of myocardial function in hypoparathyroidism causing hypocalcaemia. Heart, 1990. 63(1): p. 58-60.
    86. Bers, D.M., Cardiac excitation–contraction coupling. Nature, 2002. 415(6868): p. 198-205.
    87. Weber, K.T., R.U. Simpson, and L.D. Carbone, Vitamin D and calcium dyshomoeostasis-associated heart failure. Heart, 2008. 94(5): p. 540-1.
    88. Szent-Györgyi, A.G., Calcium regulation of muscle contraction. Biophysical journal, 1975. 15(7): p. 707-723.
    89. De Boland, A.R. and R.L. Boland, Non-genomic signal transduction pathway of vitamin D in muscle. Cellular Signalling, 1994. 6(7): p. 717-724.
    90. Weishaar, R.E. and R.U. Simpson, Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects. Am J Physiol, 1987. 253(6 Pt 1): p. E675-83.
    91. Weber, K.T., W.B. Weglicki, and R.U. Simpson, Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium. Cardiovascular Research, 2009. 81(3): p. 500-508.
    92. Ogino, K., et al., Parathyroid hormone-related protein is produced in the myocardium and increased in patients with congestive heart failure. J Clin Endocrinol Metab, 2002. 87(10): p. 4722-7.
    93. Saetrum Opgaard, O. and P.H. Wang, IGF-I is a matter of heart. Growth Horm IGF Res, 2005. 15(2): p. 89-94.
    94. Troncoso, R., et al., New insights into IGF-1 signaling in the heart. Trends in Endocrinology & Metabolism, 2014. 25(3): p. 128-137.
    95. Munns, C.F., et al., Global consensus recommendations on prevention and management of nutritional rickets. Hormone Research in Paediatrics, 2016. 85(2): p. 83-106.
    96. Hollis, B.W., et al., Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics, 2015. 136(4): p. 625-34.