1. Vitamin D status in Jordanian Infants, A Cause for Concern ? Najwa Khuri-Bulos, MD, FIDSA, Samir Faouri MD Jordan University Hospital and Al Bashir Government Hospital July 2012

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 and the fetus and newborn What is role of vitamin D in pregnancy What is the role of vitamin D in labor and birth What is the role of vitamin D in the newborn What is the relationship of vitamin D in mother and the fetus

4. WHO reference Vitamin D deficiency in pregnant women has been associated with an increased risk of pre- eclampsia and gestational diabetes. Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia, according to a study from the University of Pittsburgh Schools of the Health Sciences reported in the Journal of Clinical Endocrinology and Metabolism.

5. Vitamin D Rickets first described in the 17 th century Relationship to fat soluble vitamin and dietary vitamin D in early 20 th 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

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

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

9. 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

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

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

12. 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

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

14. 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

15. 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

16. 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

17. 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

18. Vitamin D 25 OH levels and vitamin D status Definition – <20ng/ml <50 mm/LDeficient – 20-30ng/ml 50-75 mm/LInsufficient – >30- ng/ml>75 mm/LNormal, optimal – >150 ng/ml >375 mm/L Toxic

19. 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

20. 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 D 3, which in turn becomes vitamin D 3.

21. Adequate intake of vitamin D per day Infants <12 month400 IU Children >1 yr600 IU Adults, pregnant600 IU >70 yrs800 IU Mainly obtained from fish and fortified foods or exposure to sunshine 1 ug=40 units

22. 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

23. 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

24. 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)

25. 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

26. 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

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

33. 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

34. Treatment of vitamin D deficiency ACUTE Management Age < 1 month Vitamin D: 1000 IU (25 μg) daily for 3 months. Maintenance Vitamin D: 400 IU (10 μg) daily or 150 000 IU (3750 μg) at the start of autumn.‡ Monitoring 1 month: Serum calcium and alkaline phosphatase. 1-12 months Vitamin D: 3000 IU (75 μg) daily for 3 months, or 300 000 IU (7500 μg) over 1–7 day 3 months: Serum calcium, magnesium, phosphate, alkaline phosphatase, calcidiol, parathyroid hormone. Wrist x-ray to assess healing of rickets. Annual: Calcidiol. >12 months Vitamin D: 5000 IU (125 μg) daily for 3 months, or 500 000 IU (15 000 μg) over 1–7 days. Calcitriol, 1, 25 OH vitamin D, Calcidiol, 25 oh vitamin D

35. Adequate calcium intake AgeCalcium intake 0-6 months210 mg 6-12 months270 mg 1-3 years300 mg 4-8 years800 mg 9-18 years1300 mg

36. 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 50% children 1-6 yrs< 11 ng/ml 10-20% Takruri et al, JMJ, 1-6 yrs also 30% insufficient

37. 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 Mean was 3 !!! 100 Mothers who were tested also had decreased vitamin D level. Almost uniformly less than 10

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

39. 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

40. Thank you