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
Outline about vitamin D
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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 and the fetus and newborn
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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
WHO reference
• Vitamin D deficiency in pregnant women has
been associated with an increased risk of preeclampsia 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.
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
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Vitamin D2,
Vitamin D3
Ergosterol plant sources
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
– 20-30ng/ml
– >30- ng/ml
optimal
– >150 ng/ml
<50 mm/L
50-75 mm/L
>75 mm/L
Deficient
Insufficient
Normal,
>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 7dehydrocholesterol to previtamin D3, which in
turn becomes vitamin D3.
Adequate intake of vitamin D per day
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Infants <12 month
Children >1 yr
Adults, pregnant
>70 yrs
400 IU
600 IU
600 IU
800 IU
• Mainly obtained from fish and fortified foods or
exposure to sunshine
• 1 ug=40 units
People at risk of vitamin D deficiency
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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; darkskinned 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)
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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 deficiency
ACUTE Management
Age
< 1 month
Vitamin D: 1000 IU (25 μg)
daily for 3 months.
1-12 months
Vitamin D: 3000 IU (75 μg)
daily for 3 months, or
300 000 IU (7500 μg) over
1–7 day
>12 months
Vitamin D: 5000 IU
(125 μg) daily for
3 months, or 500 000 IU
(15 000 μg) over 1–7 days.
Maintenance
Monitoring
Vitamin D: 400 IU (10 μg)
daily or 150 000 IU
(3750 μg) at the start of
autumn.‡
1 month: Serum calcium
and alkaline phosphatase.
3 months: Serum calcium,
magnesium, phosphate,
alkaline phosphatase,
calcidiol, parathyroid
hormone. Wrist x-ray to
assess healing of rickets.
Annual: Calcidiol.
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 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 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
• Mean was 3 !!!
• 100 Mothers who were tested also had
decreased vitamin D level. Almost uniformly less
than 10
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