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Vitamin D in Jordanian Infants

Vitamin D in Jordanian Infants. Najwa Khuri-Bulos Professor of Pediatrics and Infectious Disease Jordan University Hospital. Outline about vitamin D. Sources of vitamin D Classical action on bone Non classical functions Normal vitamin D intake Pts at risk of vitamin D deficiency

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Vitamin D in Jordanian Infants

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  1. Vitamin D in Jordanian Infants Najwa Khuri-Bulos Professor of Pediatrics and Infectious Disease Jordan University Hospital

  2. Outline about vitamin D • Sources of vitamin D • Classical action on bone • Non classical functions • Normal vitamin D intake • Pts at risk of vitamin D deficiency • Clinical manifestations of vitamin D deficiency • Laboratory diagnosis of vitamin D deficiency • Treatment • Status of vitamin D in jordan with special reference to children Prevention of vitamin D deficiency

  3. Vitamin D • Rickets first described in the 17th century • Relationship to fat soluble vitamin and dietary vitamin D in early 20th century . • This is the only vitamin that is synthesized by human body by interaction of skin with sunshine • Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D

  4. Vitamin D pathways for the two sources of vitamin D

  5. Definition • Vitamin D2, Ergosterol plant sources • Vitamin D3 Cholecalciferol from skin • also manufactured from lanolin • 25,0H vitamin D Calcidiol • 1,25 OH vitamin D Calcitriol

  6. Vitamin D actions • Vitamin D promotes calcium absorption in the gut • Maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevents hypocalcemic tetany. • It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts

  7. Vitamin D actions Actions on bone • Increased Bone density • Increased calcium and PO4 deposition • Decreased osteoporotic fracture

  8. Vitamin D actions Immune response • Increased regulatory T cell • Increased oxidative burst • Increased Cathelicidin • Decreased cytokine release

  9. Vitamin D actions Pregnancy • ?Decreased pre eclampsia • Decreased myopathy • Decreased calcium malabsorption • Decreased bone loss • ?Decreased risk of CS Mulligan et al, American Journal of Obstetric and Gynecology, 2010

  10. Vitamin D action Pancreas • Decreased insulin resistance • Decreased type 1 diabetes • Increased insulin secretion

  11. Vitamin D actions Children • Decreased SGA • Decreased risk of rickets • Decreased risk of hypocalcemia • Infantile cardiomyopathy if deficient • Decreased severity of RSV infection • Increased incidence of asthma if deficient

  12. Sources of vitamin D • Normal diets < 10% • Must be synthesized by the skin or taken as dietary supplement • Skin, must have direct exposure to sunshine 10-15 minutes at noon hours • Exposure not acceptable behind glass • No sun block applied • Dark skin people need more exposure to have same level of vitamin D

  13. Vitamin D in the newborn • Highly correlated with vitamin D in the pregnant mother. Fetus totally dependent on maternal sources of vitamin D and Calcium • After birth, Breast milk is a very poor source of vitamin D, only 10-40 Units/Litre • Hence Must supplement infants very early in life • Infants need 400 IU/ per day • Even formula fed babies need vitamin D supplementation

  14. Vitamin D status • 1 nmole/litre = 0.4 ngm /ml • Vitamin D levels are Inversely related to parathormone levels • These level off at 30-40 nanograms determined to be the adequate range • Calcium absorption increased at > 30 nanograms

  15. Vitamin D 25 OH levels and vitamin D status • Definition • <20ng/ml <50 mm/L Deficient • 20-30ng/ml 50-75 mm/L Insufficient • >30- ng/ml >75 mm/L Normal, optimal • >150 ng/ml >375 mm/L Toxic

  16. Vitamin D sources • Dietary • Supplementation • Sunlight • Wavelength 290-315 penetrates the skin and converts 7 dehydrocholesterol to previtamin D3 • Any excess of these is destroyed by sunlight. There is no toxicity from sun exposure. • Vitamin D from the skin and dietary sources is metabolized by the liver to become 25 OH and the final 1 hydroxylation step occurs in the kidney to lead to 1, 25 OH vitamin D which is the active form • This final renal step is highly regulated by parathormone and serum calcium and PO4 levels

  17. Sun exposure and vitamin D • Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3.

  18. Adequate intake of vitamin D per day • Infants <12 month 400 IU • Children >1 yr 600 IU • Adults, pregnant 600 IU • >70 yrs 800 IU • Mainly obtained from fish and fortified foods or exposure to sunshine • 1 ug=40 units

  19. People at risk of vitamin D deficiency • Breast fed infants • Older adults • People with limited sun exposure • People with dark skin • People with fat malabsorption • People with BMI>30

  20. Causes of vitamin D deficiency in children and adolescents • Reduced intake or synthesis of vitamin D3 • Being born to a vitamin D-deficient mother; dark-skinned women, or women of who actively avoid exposure to sunlight or are veiled • Prolonged breastfeeding • Dark skin colour • Reduced sun exposure — chronic illness or hospitalisation, intellectual disability, and excessive use of sunscreen • Low intake of foods containing vitamin D

  21. Causes of vitamin D deficiency in children and adolescents • Abnormal gut function or malabsorption • Small-bowel disorders (eg, coeliac disease) • Pancreatic insufficiency (eg, cystic fibrosis) • Biliary obstruction (eg, biliary atresia)

  22. Causes of vitamin D deficiency in children and adolescents • Reduced synthesis or increased degradation of 25-OHD or 1,25-(OH)2D • Chronic liver or renal disease • Drugs: rifampicin, isoniazid and anticonvulsants

  23.  Osseous signs of vitamin D deficiency (common to less common) • Swelling of wrists and ankles • Rachitic rosary (enlarged costochondral joints felt lateral to the nipple line) • Genu varum, genu valgum or windswept deformities of the knee • Frontal bossing • Limb pain and fracture • Craniotabes (softening of skull bones, usually evident on palpation of cranial sutures in the first 3 months) • Hypocalcaemia — seizures, carpopedal spasm • Myopathy, delayed motor development • Delayed fontanelle closure • Delayed tooth eruption • Enamel hypoplasia • Raised intracranial pressure • secondary hyperparathyroidism

  24. Radiological features • Cupping, splaying and fraying of the metaphysis of the ulna, radius and costochondral junction • Coarse trabecular pattern of metaphysis • Osteopenia • Fractures

  25. Treatment of Hypocalcemia < 1 month of age • 10% calcium gluconate: 0.5 mL/kg (max 20 mL) intravenously over 30–60 minutes. • Calcium: 40–80 mg/kg/day (1–2 mmol/kg/day) orally in 4–6 doses, • Calcitriol ( vitamin D3) : 50–100 ng/kg/day or in 2–3 doses until serum calcium level is > 2.1 mmol/L or 8 mg/L

  26. Treatment of vitamin D deficiency Calcitriol , 1, 25 OH vitamin D, Calcidiol, 25 oh vitamin D

  27. Adequate calcium intake

  28. Recent Studies on vitamin D in Jordanians 2011, Batieha Et al Ann Nutr Met • 37% females were deficient • 5.6% of males were deficient 2010 Abdul Razzak , Pediatric International 28% deficient, 16% severe Association with breast feeding was found National micronutrient survey 2010 women deficient < 12 ng/ml > 50% children 1-6 yrs< 11 ng/ml 10-20% Takruri, Khuri-Bulos et al , JMJ, 1-6 yrs also 30% insufficient

  29. Study on newborn and pregnant mothers and vitamin D • Ongoing study of vitamin D in newborn • More than 3000 vitamin D levels obtained in the first day of life • Range from 0.1- 15 ng/ml • Cut off for this is 20 ng/ml • 99.8 were vitamin D deficient below 10 ng/ml • Mean was 3 ng/ml !!! • 100 Mothers who were tested also had decreased vitamin D level. Almost uniformly less than 10ng/ml

  30. Vitamin D levels in newborns in Jordan Overwhelming majority >99% are deficient < 15 nanograms/ml

  31. What should be done • Increased sun exposure, not consistent with current social norms • Supplementation of the different age groups • Fortification of food items, most useful • Which food item?? Oil preferable but flour more feasible since it is cheaper and is the main staple food • For infants must give vitamin d drops • Pregnant women should be studied further and supplementation during pregnancy must be done

  32. Thank you

  33. Vitamin D activity • Activated T lymphocytes and macrophages have increased VDR This stimulates antibody mediated and phagocyte mediated cytotoxicity • Clinical association with asthma and RSV if cord blood vitamin D is deficient • Increased risk of cesarian section also with vitamin D deficiency

  34. Metabolism of 25-Hydroxyvitamin D to 1,25-Dihydroxyvitamin D for Nonskeletal Functions. Holick MF. N Engl J Med 2007;357:266-281.

  35. Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone Metabolism. Holick MF. N Engl J Med 2007;357:266-281.

  36. The immune system and Vitamin D • Calcitriol (I,25, OH) has immune modulating function • First described with sarcoidosis • Calcitriol produced by macrophages in the granulomas lead to hypercalcemia • Calcitriol also inhibits proliferation of MTB in cells • This is not subject to feedback as is the kidney • Vitamin D deficiency has been shown to increase the risk of infection especially respiratory infection

  37. Vitamin D functions • Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation • Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D • Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements and has a fairly long circulating half-life of 15 days

  38. Sun exposure and vitamin D • Complete cloud reduces UV energy by 50%; shade • UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D • Sunscreens with a sun protection factor (SPF) of 8 or more appear to block vitamin D-producing UV rays

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