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European Journal of Pediatrics

, Volume 178, Issue 7, pp 1087–1093 | Cite as

The relationship between serum vitamin D levels and intima-media thickness in term infants

  • Didem ArmanEmail author
  • Zeynep Çetiner
Original Article

Abstract

Increasing epidemiologic evidence indicates that vitamin D deficiency is linked to a series of diseases, including cardiovascular disease. This prospective study was designed to determine the relationship between 25 hydroxyvitamin D (25(OH)D) level and aortic intima-media thickness (aIMT) and carotid intima-media thickness (cIMT) in term healthy neonates. A total of 135 term, healthy infants were included in the study. Ultrasonographic measurements were performed at 24–48 h after birth. Blood samples were obtained from the umbilical cord at birth. The neonates were divided into four groups according to serum 25(OH)D vitamin levels. For the entire cohort, the mean 25 hydroxyvitamin D level was found to be 15.17 ± 9.66 ng/mL. The mean values of cIMT and aIMT measurements were 0.386 ± 0.052 and 0.412 ± 0.076 mm, respectively. In group 4, mean and maximum aIMT measurements were significantly lower than the other groups (p = <0.001 and 0.001, respectively). We did not observe any significant difference between groups regarding cIMT measurements. Correlation was found between aIMT and 25 hydroxyvitamin D levels (r = 0.295 p = < 0.001).

Conclusion: We conclude that vitamin D deficiency may be associated with early relative intima-media thickening of the aorta already in the first week of life.

What is Known:

• Vitamin D deficiency is linked to a series of diseases, including cardiovascular disease.

• Studies in adults and high-risk children have shown that the measurement of the intima-media thickness represents an excellent marker of subclinical atherosclerosis.

What is New:

This is the first study evaluating the relationship between 25(OH)D vitamin level and intima-media thickness in term healthy neonates.

• Vitamin D deficiency in neonates may induce atherosclerosis early in life and the aortic intima-media thickness measurements may be used as an early marker for detection.

Keywords

Atherogenesis Aortic intima-media thickness Carotid intima-media thickness 25 hydroxyvitamin D 

Abbreviations

25(OH)D

25 hydroxyvitamin D

aIMT

Aortic intima-media thickness

cIMT

Carotid intima-media thickness

Notes

Financial support

This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Authors’ contribution

Design of the study, data analysis, preparation of the manuscript : DA

Performing ultrasonographic studies, data analysis : ZC

Compliance with ethical statements

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the local committee.

Informed consent

Informed parental consent was obtained for all infants.

References

  1. 1.
    Arnson Y, Itzhaky D, Mosseri M, Barak V, Tzur B, Agmon-Levin N, Amital H (2013) Vitamin D inflammatory cytokines and coronary events: a comprehensive review. Clin Rev Allergy Immunol 45:236–247CrossRefGoogle Scholar
  2. 2.
    Ballard J, Khoury J, Wedig K, Wang L, Eilers-Walsman B, Lipp R (1991) New Ballard Score, expanded to include extremely premature infants. J Pediatr 119:417–423CrossRefGoogle Scholar
  3. 3.
    Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischemic disease. Lancet 2:577–580CrossRefGoogle Scholar
  4. 4.
    Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam study. Circulation 96:1432–1437CrossRefGoogle Scholar
  5. 5.
    Codoner-Franch P, Tavarez-Alonso S, Simo-Jorda R, Laporta-Martín P, Carratalá-Calvo A, Alonso-Iglesias E (2012) Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children. J Pediatr 161:848–854CrossRefGoogle Scholar
  6. 6.
    Gertner JM, Glassman MS, Coustan DR, Goodman DB (1980) Fetomaternal vitamin D relationships at term. J Pediatr 97:637–640CrossRefGoogle Scholar
  7. 7.
    Gezmish O, Tare M, Parkington HC, Morley R, Porrello ER, Bubb KJ, Black MJ (2010) Maternal vitamin D deficiency leads to cardiac hypertrophy in rat offspring. Reprod Sci 17:168–176CrossRefGoogle Scholar
  8. 8.
    Giovannucci E, Liu Y, Hollis BW, Rimm EB (2008) 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 168:1174–1180CrossRefGoogle Scholar
  9. 9.
    Harrington J, Pe˜na AS, Gent R, Hirte C, Couper J (2010) Aortic intima media thickness is an early marker of atherosclerosis in children with type 1 diabetes mellitus. J Pediatr 156:237–241CrossRefGoogle Scholar
  10. 10.
    Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80:1678–1688CrossRefGoogle Scholar
  11. 11.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 96(7):1911–1930CrossRefGoogle Scholar
  12. 12.
    Hondappanavar A, Singh Sodhi K, Dutta S, Saxena AK, Khandelwal N (2013) Quantitative ultrasound measurement of intima–media thickness of abdominal aorta and common carotid arteries in normal term newborns. Pediatr Cardiol 34:364–369CrossRefGoogle Scholar
  13. 13.
    Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Rönnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT (2001) Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation 104:2943–2947CrossRefGoogle Scholar
  14. 14.
    Kendrick J, Targher G, Smits G, Chonchol M et al (2009) 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third National Health and Nutrition Examination Survey. Atherosclerosis 205:255–260CrossRefGoogle Scholar
  15. 15.
    Koklu E, Kurtoglu S, Akcakus M, Yikilmaz A, Coskun A, Gunes T (2007) Intima-media thickness of the abdominal aorta of neonate with different gestational ages. J Clin Ultrasound 35:491–497CrossRefGoogle Scholar
  16. 16.
    Koklu E, Ozturk MA, Kurtoglu S, Akcakus M, Yikilmaz A, Gunes T (2007) Aortic intima-media thickness, serum IGF-I, IGFBP-3, and leptin levels in intrauterine growth-restricted newborns of healthy mothers. Pediatr Res 62:704–709CrossRefGoogle Scholar
  17. 17.
    Kosecik M, Ertas T (2007) Dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Pediatr Int 49:397–399CrossRefGoogle Scholar
  18. 18.
    Lubchenco LC, Hansman C, Dresseler M, Boyd E (1963) Intrauterine growth as estimated from liveborn birth-weight data 24 to 42 weeks of gestation. Pediatrics 32:793–800Google Scholar
  19. 19.
    Maiya S, Sullivan I, Allgrove J, Yates R, Malone M, Brain C, Archer N, Mok Q, Daubeney P, Tulloh R, Burch M (2008) Hypocalcaemia and vitamin D deficiency: an important, but preventable, cause of life-threatening infant heart failure. Heart 94:581–584CrossRefGoogle Scholar
  20. 20.
    McGill HC Jr, McMahan CA, Herderick EE, Tracy RE, Malcom GT, Zieske AW, Strong JP (2000) Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. PDAY Research Group. Pathobiological determinants of atherosclerosis in youth. Arterioscler Thromb Vasc Biol 20:836–845CrossRefGoogle Scholar
  21. 21.
    Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M (2008) Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 122:398–417CrossRefGoogle Scholar
  22. 22.
    Noyola-Martínez N, Díaz L, Avila E, Halhali A, Larrea F, Barrera D (2013) Calcitriol downregulates TNF-α and IL-6 expression in cultured placental cells from preeclamptic women. Cytokine 61:245–250CrossRefGoogle Scholar
  23. 23.
    Pauciullo P, Iannuzzi A, Sartorio R, Irace C, Covetti G, Di Costanzo A, Rubba P (1994) Increased intima-media thickness of the common carotid artery in hypercholesterolemic children. Arterioscler Thromb 14:1075–1079CrossRefGoogle Scholar
  24. 24.
    Peterson C, Balechia A (2014) Vitamin D deficiency and obesity: a tale of two epidemics. Mo Med 111:49–53Google Scholar
  25. 25.
    Reis JP, von Muhlen D, Michos ED, Miller ER, Appel LJ, Araneta MR, Barrett-Connor E (2009) Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis. Atherosclerosis 207:585–590CrossRefGoogle Scholar
  26. 26.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809CrossRefGoogle Scholar
  27. 27.
    Salonen JT, Salonen R (1991) Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 11:1245–1249CrossRefGoogle Scholar
  28. 28.
    Sehgal A, Doctor T, Menahem S (2013) Cardiac function and arterial biophysical properties in small for gestational age infants: postnatal manifestations of fetal programming. J Pediatr 163:1296–1300CrossRefGoogle Scholar
  29. 29.
    Sehgal A, Allison BJ, Gwini SM, Menahem S, Miller SL, Polglase GR (2018) Vascular aging and cardiac maladaptation in growth-restricted preterm infants. J Perinatol 38:92–97CrossRefGoogle Scholar
  30. 30.
    Skilton MR, Evans N, Griffiths KA, Harmer JA, Celermajer DS (2005) Aortic wall thickness in newborns with intrauterine growth restriction. Lancet 365:1484–1486CrossRefGoogle Scholar
  31. 31.
    Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, Bischoff-Ferrari HA, Cavalier E, Ebeling PR, Fardellone P, Gandini S, Gruson D, Guérin AP, Heickendorff L, Hollis BW, Ish-Shalom S, Jean G, von Landenberg P, Largura A, Olsson T, Pierrot-Deseilligny C, Pilz S, Tincani A, Valcour A, Zittermann A (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev 9:709–715CrossRefGoogle Scholar
  32. 32.
    Sun J, Zhong W, Gu Y, Groome LJ, Wang Y (2014) 1,25(OH)2D3 suppresses COX-2 up-regulation and thromboxane production in placental trophoblast cells in response to hypoxic stimulation. Placenta 35:143–145CrossRefGoogle Scholar
  33. 33.
    Takeda M, Yamashita T, Sasaki N, Nakajima K, Kita T, Shinohara M, Ishida T, Hirata K (2010) Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions. Arterioscler Thromb Vasc Biol 30:2495–2503CrossRefGoogle Scholar
  34. 34.
    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035.  https://doi.org/10.1136/bmj.g2035 CrossRefGoogle Scholar
  35. 35.
    Toikka JO, Laine H, Ahotupa M, Haapanen A, Viikari JS, Hartiala JJ, Raitakari OT (2000) Increased arterial intima-media thickness and in vivo LDL oxidation in young men with borderline hypertension. Hypertension 36:929–933CrossRefGoogle Scholar
  36. 36.
    Wagih HM, Hashem HE, Hassan ZA, Algaidi SA (2018) Modulation of S100 and smooth muscle actin-α immunoreactivity in the wall of aorta after vitamin D administration in rats with high fat diet. Cell Mol Biol 64:21–28CrossRefGoogle Scholar
  37. 37.
    Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511CrossRefGoogle Scholar
  38. 38.
    Weng S, Sprague JE, Oh J, Riek AE, Chin K, Garcia M, Bernal-Mizrachi C (2013) Vitamin D deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One 8:54625.  https://doi.org/10.1371/journal.pone.0054625 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of NeonatologyOrdu University Maternity and Children’s Research and Training HospitalOrduTurkey
  2. 2.Department of RadiologyOrdu University Maternity and Children’s Research and Training HospitalOrduTurkey

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