Download VITAMINS D Deficiency Dr Nahid Aslani General Pediatrics Medical

VITAMINS D
Deficiency
Dr Nahid Aslani
General Pediatrics
Medical University Of Isfahan
Vitamin Facts
 Organic substances that are essential in minute quantities
to the nutrition of most animals and some plants, act
especially as coenzymes in the regulation of metabolic
processes but do not provide energy.
VITAMIN D DEFICIENCY
• Vitamin D, a lipid-soluble vitamin and prohormone
is known to play an important role in bone metabolism
through regulation of calcium and phosphate homeostasis.
EPIDEMIOLOGY
Vitamin D deficiency is a global health problem.
With all the medical advances of the century, vitamin D
deficiency is still epidemic.
Over a billion people worldwide are vitamin D deficient
or insufficient.
• The high prevalence of hypovitaminosis D in a number
of developing countries exists despite the fact that a
large number of these countries lie in zones that have
sufficient sunlight for vitamin D synthesis for most if not
all of the year.
METABOLISM AND FORMS OF VITAMIN D
• Vitamin D is a prohormone that is synthesized in the
skin after exposure to ultraviolet radiation.
• Less than 10 percent of vitamin D comes from dietary
sources in the absence of food fortification or use of
supplements.
METABOLISM AND FORMS OF VITAMIN D
• Cholecalciferol (vitamin D3)
• Ergocalciferol ( vitamin D2)
• Calcidiol (25-hydroxyvitamin D or 25[OH]D)
• Calcitriol (1,25-hydroxyvitamin D or 1,25[OH]2D)
Pathophysiology
CAUSES OF VITAMIN D DEFICIENCY
Lack of vitamin D in the diet, often in conjunction with
inadequate sun exposure .
Inability to absorb vitamin D from the intestines .
Inability to process vitamin D due to kidney or liver disease .
 Skin pigmentation determines the duration of sun exposure
necessary to achieve a certain concentration of vitamin D.
 MED (the amount of UV-B required to produce slight
pinkness of the skin), exposure to the equivalent MED of
whole-body UV-B results in similar vitamin D levels.
Exposure to sunlight
• During the spring, summer, and fall, 10 to 15 minutes of
sun exposure between between 1000 to 1500 hours
(10:00 AM and 3:00 PM) is sufficient for adequate
vitamin D synthesis in light skinned individuals .
Sunscreen
• Sunscreen absorbs UV-B and some UV-A light and prevents
it from reaching and entering the skin.
• A sun screen with a sun protection factor (SPF) of 8 can
decrease vitamin D3 synthetic capacity by 95%, and SPF 15
can decrease it by 98% .
Latitude and Season
• In the winter months, the rays of the sun enter the atmosphere at an oblique
angle, UV-B photons have to pass through a greater distance of the
atmosphere, and more UV-B photons are absorbed by ozone.
• Beyond a latitude of 40° and during winter, little or no UV-B radiation
reaches the surface of the earth.
• Exposure to the sun is not recommended as a source of
vitamin D for infants and children due to the potential
long-term risks of skin cancer
Other Causes Of Vitamin D Deficiency
 Poor Maternal Vitamin D Status
Prematurity
Exclusive Breastfeeding
Obesity
Malabsorption(inflammatory bowel disease, CF, cholestasis)
Medications
CLINICAL MANIFESTATIONS
Rickets
Osteomalacia
Biochemical changes
Radiographic Scoring System of Wrist
Radiographic Scoring System of Knee
Current Researches
Immunological conditions
 Multiple Sclerosis
 Type 1 diabetes
 Inflammatory bowel disease
 Childhood Asthma and AD
Mood disorders
Cardiovascular disease
Cancers(breast, prostate, and colon)
Current Researches
 Hypertension
Hyperglycemia
 The metabolic syndrome
Respiratory infections
VITAMIN D SUPPLEMENTATION
Breast and Formula Fed Infants
• Vitamin D content of breast milk is low (15 to 50 IU/L)
• Infant formulas usually providing at least 400 IU/L.
American Academy of Pediatrics, November 2012
• A supplement of 400 IU per day of vitamin D is
recommended for all breastfed infants and children
beginning in the first few days of life
American Academy of Pediatrics, July , 2015
• Maternal vitamin D supplementation with 6400 IU/day
safely supplies breast milk with adequate vitamin D to
satisfy her nursing infant’s requirement and offers an
alternate strategy to direct infant supplementation.
AAP new guidelines for preterm infants
• For babies that weigh less than 1500 g , they should get
biochemical testing for bone mineral status starting 4 to
5 weeks after birth.
• If the babies’ serum alkaline phosphatase activity is
greater than 800 IU/L to 1000 IU/L or the baby is getting
fractures, they should receive radiographic evaluation
for rickets and treated with calcium and phosphorus as
necessary.
Guidelines for preterm infants
For preterm and very low birth weight infants that weigh less
than 1500 g, they should get 200 to 400 IU of vitamin D/day.
For infants that weigh over 1500 g, they should get 400 IU/day.
OTHER AGE GROUPS
• Healthy children 1 to 18 years of age – 600 International
Units (15 micrograms) daily
• In pregnant and lactating women, the RDA for vitamin
D is 600 int. units , which is the same as for women who
are not pregnant .
2011 Pediatrics
Iranian Guideline for Vitamin D Supplementation
0-24 Month :400 IU /day from 3-5 days after birth.
2 -12 years: 800 IU/day (50,000 IU every 2 month)
12-70 years: 50,000 IU every 1 month.
Above 70 years: 50.000 IU every 2 weeks.
SCREENING FOR VITAMIN D
DEFICIENCY
SCREENING
Exclusively breastfed or premature infants
Infants and young children with nonspecific symptoms
such as poor growth, gross motor delays, irritability .
Dark-skinned infants and children
Children on anticonvulsants or chronic glucocorticoids
Children with chronic diseases
Children with low dietary intake of vitamin D
Obesity, amenorrhea, immobilization, chronic kidney or
liver disease.
MEASUREMENT
25(OH)D is the major circulating form of vitamin D with
a half-life of 2-3 weeks and its levels are the best
available indicators of vitamin D status.
Although 1, 25 (OH)2D (calcitriol) is the active form, it
has a half-life of only 4 hours and it is not a good
indicator of vitamin D stores .
SCREENING
 Serum ALP if elevated for age (500 IU/L in neonates
and 1000 IU/L in children up to 9 years of age
All children with radiographic evidence of rickets have
low vitamin D levels, not all have high ALP levels, and
the wrist radiograph may be the most reliable test for
detecting subclinical rickets.
GOLD STANDARD vitamin D ASSAY
High performance liquid chromatography (HPLC)
 liquid chromatography-mass spectroscopy (LC-MS)
 Radioimmunoassays also perform well enough for clinical use
MEASUREMENT
 Significant controversy has been associated with
determining standards of vitamin D sufficiency,
insufficiency, and deficiency.
2016 Global Consensus recommendations
Vitamin D sufficiency:
20 to 100 ng/mL (50 to 250 nmol/L)
Vitamin D insufficiency:
12 to 20 ng/mL (30 to 50 nmol/L)
Vitamin D deficiency:
<12 ng/mL (<30 nmol/L)
Biochemical changes
TREATMENT
 Vitamin D replacement therapy is necessary for :
children presenting with low vitamin D levels (25(OH)D
<20 ng/mL (50 nmol/L))
Rickets.
Endocrine Society Guideline
• Infants <12 months old:
• 2000 IU/day for six to twelve weeks, followed by
maintenance dosing of at least 400 IU/day.
• Children >12 months old:
• 2000 IU/day for six to twelve weeks, or 50,000 IU per
week for six weeks , followed by maintenance dosing of
600 to 1000 IU/day.
• Infants <1 month old
1000 IU/day for six weeks, followed by maintenance dosing of at
least 400 IU/day.
• Infants 1 to 12 months old
1000 to 2000 IU/day for six weeks, followed by maintenance
dosing of at least 400 IU/day.
• Children >12 months old
2000 IU/day for six weeks, or 50,000 IU per week for six weeks ,
followed by maintenance dosing of 600 to 1000 IU/day.
Global Consensus Recommendations
• Infants ≤12 months old:
• 2000 IU/day for three months , followed by maintenance
dosing of 400 IU/day.
• Children >12 months to 12 years old:
• 3000 to 6000 IU/day for three months, followed by
maintenance dosing of 600 IU/day.
• Children >12 years old:
• 6000 IU/day for three months, followed by maintenance
dosing of 600 IU/day.
• Children with obesity, malabsorptive diseases, or those
on medications that impact vitamin D metabolism may
require higher replacement doses (two to three times
higher than in children without these conditions),
followed by higher maintenance dosing .
“stoss” therapy
• Short-term administration of high dose vitamin D,
known as “stoss therapy”, is an effective alternative.
• A single dose of 600,000 int. units of vitamin D as an
intramuscular injection is an excellent solution for
persistent non-compliance.
Calcitriol (1,25(OH)2D)
Is not necessary, except in conditions of severe vitamin D
deficiency with severe symptomatic hypocalcemia.
Dose of 20 to 100 ng/kg/day with intravenous calcium
gluconate and high doses of vitamin D may normalize
plasma calcium levels more rapidly than standard vitamin
D treatment( no role in building up vitamin D stores).
Calcium supplementation
Hypocalcemia should be treated with calcium supplements
at a dose of 10 to 20 mg/kg of elemental (1 to 2 mL/kg of 10
percent calcium gluconate)
Calcium replacement at doses of 30 to 75 mg/kg/day of
elemental calcium given in two to three divided doses for
two to four weeks, until vitamin D doses have been reduced
to maintenance levels of 600 to 1000.
 Prevention of Nutritional Rickets include administration of
a daily dose of 500 mg of elemental oral calcium.
2011 Pediatrics
Borderline vitamin D levels
25(OH)D between 12 and 20 ng/mL (30 to 50 nmol/L)
Not usually give vitamin D replacement therapy unless
there are other signs of vitamin D deficiency or
important risk factors ( very low nutritional intake or
perinatal risk factors) .
Monitoring 25(OH)D levels in these children
periodically, and initiating treatment if levels fall below
12 ng/mL (30 nmol/L).
Follow-up
 Patients with rickets.
Patients without rickets but with low vitamin D levels
and biochemical changes .
Patients presenting with only low levels of vitamin D and
no other biochemical changes or evidence of rickets.
Patients with rickets
Radiographic healing , normalization of serum
25(OH)D, PTH, calcium and phosphorus levels, and
long-term maintenance of vitamin D sufficiency.
Complete radiologic healing may take months, but
changes are evident in 1 week.
 A radiograph should also be repeated at 3 months.
Patients without rickets but with low vitamin D
levels and biochemical changes
Check serum 25(OH)D levels and other chemistries after
six to eight weeks of high-dose therapy, then again after
several months of maintenance therapy, then annually
thereafter.
Patients presenting with only low levels of vitamin D and
no other biochemical changes or evidence of rickets
Check 25(OH)D levels after two to three months, then as
needed thereafter, depending on the adequacy of the
patient's intake and adherence to maintenance
supplements.
Vitamin D Excess
• Consuming too much vitamin D through diet alone is
not likely unless you routinely consume large amounts
of cod liver oil. It is much more likely to occur from high
intakes of vitamin D in supplements.
EXCESS
The recommended upper limits for long-term vitamin D
intake are 1,000 IU for children <1 year old and 2,000
IU for older children and adults.
Vitamin D intoxication has been documented in adults
taking more than 60,000 international units per day.
Laboratory Findings
 Hypercalcemia
Extremely elevated levels of 25-D (>150ng/mL)
Hyperphosphatemia
 PTH levels are appropriately decreased
 Nephrocalcinosis
Clinical Manifestations
Symptoms of acute intoxication are due to
hypercalcemia and include confusion, polyuria,
polydipsia, anorexia, vomiting, and muscle weakness.
Chronic intoxication may cause nephrocalcinosis,
bone demineralization and pain.
Treatment
The treatment of vitamin D intoxication focuses on
control of hypercalcemia.
The mainstay of the initial treatment is aggressive
therapy with normal saline, often in conjunction with a
loop diuretic to further increase calcium excretion.
Treatment
 Glucocorticoids
Calcitonin
Bisphosphonates
Hemodialysis
Additional sources of vitamin D such as multivitamins
and fortified foods should be eliminated or reduced.