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– 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

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

Vitamin D pathways for the two sources of vitamin D

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

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

Vitamin D actions

Actions on bone

• Increased Bone density• Increased calcium and PO4 deposition• Decreased osteoporotic fracture

Vitamin D actions

Immune response• Increased regulatory T cell• Increased oxidative burst• Increased Cathelicidin• Decreased cytokine release

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

Vitamin D action

Pancreas• Decreased insulin resistance• Decreased type 1 diabetes• Increased insulin secretion

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

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

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

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

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

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

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.

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

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

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

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)

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

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

Radiological features

• Cupping, splaying and fraying of the metaphysis of the ulna, radius and costochondral junction

• Coarse trabecular pattern of metaphysis• Osteopenia• Fractures

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

Treatment of vitamin D deficiencyACUTE ManagementAge< 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 monthsVitamin 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 monthsVitamin 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

Adequate calcium intake

Age Calcium intake

0-6 months 210 mg

6-12 months 270 mg

1-3 years 300 mg

4-8 years 800 mg

9-18 years 1300 mg

Recent Studies on vitamin D in Jordanians

2011, Batieha Et al Ann Nutr Met– 37% females were deficient– 5.6% of males were deficient2010 Abdul Razzak , Pediatric International

28% deficient, 16% severeAssociation with breast feeding was found

National micronutrient survey 2010women 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

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

Vitamin D levels in newborns in Jordan

Overwhelming majority >99% are deficient < 15 nanograms/ml

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

Thank you

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

Metabolism of 25-Hydroxyvitamin D to 1,25-Dihydroxyvitamin D for Nonskeletal Functions.

Holick MF. N Engl J Med 2007;357:266-281.

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.

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

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

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