Question I. A vitamin D deficient mother will give birth. A. True B. False. Answer A

Vitamin D Vitamin D

Jatinder Bhatia MD FAAP

Jatinder Bhatia, MD, FAAP

Question I

† A vitamin D deficient mother will give birth to an infant ith Vit D deficienc

to an infant with Vit D deficiency

† A. True B F l

† B. False

† Answer A

Question II

† Human breast milk has adequate amounts of Vitamin D to s stain the bone health of a

Vitamin D to sustain the bone health of a healthy term infant

† A true

† A. true B. False

† Answer: B

† Answer: B

Question III

† Chronic Vitamin D deficiency presents with

† A. Decreased bone mineralization

† A. Decreased bone mineralization

† B. Hypomagnesemia

† C. Seizures

† Answer: A

Causes

† Inadequate exposure to sunlight

l b i i i l i h

† Malabsorption [intestinal resection, short bowel syndrome, cystic fibrosis]

† Minimal amounts in breast milk

M di ti [dil ti h b bit l

† Medications [dilantin, phenobarbital,

rifampin]

Frequency

† Highest among elderly, 60% of nursing home residents 57% hospitali ed patients

residents, 57% hospitalized patients

† Healthy young adults: nearly 2/3 of young adults are vitamin D deficient by end of winter in Boston

winter in Boston

† Canada and Europe similar to US

† Significantly higher prevalence of deficiency

in middle eastern countries, women>men ,

Vitamin D Deficiency

† Rickets

E i i D d fi i

„ Extreme vitamin D deficiency

„ Peak incidence 3 to 18 months of age

„ State of deficiency occurs months before rickets become obvious

„ May present with hypocalcemic seizures, growth failure lethargy irritability predisposition to

failure, lethargy, irritability, predisposition to

respiratory infections during infancy

Vitamin D Deficiency

† Rickets is preventable

† Cases of rickets due to vitamin D deficiency and

† Cases of rickets due to vitamin D deficiency and decreased exposure to sunlight continue to be

reported in the US and other western countries reported in the US and other western countries

† Exclusive breast feeding and darker skin

i i

pigmentation

† Not limited to infancy and early childhood, teens

reported

Vitamin D Deficiency

† Two types of presentations [Arch Dis Child 2004;

89:781-784]

89:781 784]

„ Symptomatic hypocalcemia occurring during periods of rapid growth

periods of rapid growth

„ Chronic: rickets and/or decreased bone

i li ti l i t ti

mineralization; normocalcemia or asymptomatic

hypocalcemia

Vitamin D

† Two forms

„ D ₂ , ergocalciferol, synthesized by plants

„ D ₂ , ergocalciferol, synthesized by plants

„ D ₃ , cholecalciferol, synthesized by mammals

„ D _{3 3} main source for humans

†

Synthesis in the skin, UV-B 290-315nm converts 7- dehydrocholesterol into previtamin D3

†

Previtamin D transformed to D >>binds with D-binding protein

†

Previtamin D

transformed to D

>>binds with D-binding protein

>> liver>>25-hydroxyvitamin D

†

25-OH-D undergoes another hydroxylation in the kidney >>1,25- dihydroxyvitamin D

dihydroxyvitamin D

†

Vitamin D, a prehormone, is involved in many metabolic

processes

Vitamin D

† Prevention of deficiency and achieving adequate intake of vitamin D and calcium adequate intake of vitamin D and calcium throughout childhood may reduce risk of

osteoporosis long-latency disease processes osteoporosis, long-latency disease processes in adults

Vit i D t l i di t i f d i

† Vitamin D as a natural ingredient in foods is limited

„ Fatty fish, fish oils, liver, egg yolks of D

supplemented chickens

Vitamin D

† Innate immunity

i f i f i

† Prevention of infections

† Auto-immune diseases [multiple sclerosis,

† Auto immune diseases [multiple sclerosis, rheumatoid arthritis]

B t i t t l t l

† Breast, ovarian, prostate, colorectal cancers

† Type-2 diabetes mellitus yp

† May decrease Type-1 diabetes mellitus

Vitamin D deficiency

Stages

Stage I: 25-OH-D decreases

hypocalcemia

Stage II: 25-OH-D decreases

PTH>demineralizes bone

Stage III: hypocalcemia Hypophosphatemia

Increased alk phos hypocalcemia

Increased Alk Phos Bone dimineralization

Clinical Signs

† Dietary Ca absorption decreases from 30-40%

to 10 15% ith D deficienc to 10-15% with D deficiency

† Low 25-OH-D >>PTH in older infants,

children and teens>>mobilizes calcium from bone>>reduction in bone mass>>fractures

bone reduction in bone mass fractures

† Rickets

„ Enlargement of skull, joints, rib cage

„ Osteomalacia, osteopenia p

Metabolic Bone Disease

Recommended Daily Intake

† Initially, based on data from US, Norway and China, 200IU/d was recommended

200IU/d was recommended

† This dose prevented physical signs of deficiency and maintained 25 OH D > 27 5 nmol/L

maintained 25-OH-D > 27.5 nmol/L

† 400 IU/d not only prevented, but, also treated rickets

† Linking other biomarkers with vitamin D deficiency

has led to concerns about the lower dose

Defining Vitamin D deficiency

† Adults: 25-OH-D concentration < 50 nmol/L

† Ad lts: Ins fficienc 50 80 nmol/L

† Adults: Insufficiency, 50-80 nmol/L

† No consensus regarding concentration that defines these in infants and children

† 200IU/d will not maintain 25-OH-D >50 nmol/L

† 400 IU/d will maintain serum 25-OH-D >50

† 400 IU/d will maintain serum 25-OH-D >50

nmol/L in exclusively breastfed infants

Sunlight exposure and Vitamin D

† Full body exposure during summer, 10-15 min, adult with lighter pigmentation:

10-20,000IU D3 in 24h

† 5 10 times more exposure

† 5-10 times more exposure with darker skin

† Skin pigmentation, body p g , y mass, latitude and season, cloud cover, air pollution, clothing and sunscreen

clothing and sunscreen

† US: average of 93% of

time spent indoors p

Sunlight Exposure

† CDC, AAP, American Cancer Society

Ri k f i ki

„ Risks for various skin cancers

„ Age may be more important than total sunlight exposure over a lifetime

„ Infants < 6 months: no direct sunlight g

„ Protective clothing and sunscreen

„ Vitamin D supplementation

„ Vitamin D supplementation

Pregnancy, Vitamin D and the Fetus

† Maternal deficiency can occur with restricted y vitamin D intake and lack of sun exposure

† Data suggest that doses >1000 IU per day of

† Data suggest that doses >1000 IU per day of vitamin D are necessary to achieve 25-OH-D

i 50 l/L i

concentrations > 50 nmol/L in pregnant women

† Vit D deficient mother will give birth to a Vit D f g

deficient neonate

Pregnancy, Vitamin D and the Fetus

† Adequate nutritional vitamin D status important d ring pregnanc

important during pregnancy

† Association with better weight gain, correlation with head circumference

† Improved bone mineral content and bone

† Improved bone mineral content and bone mass at 9 years of age

† 400 IU [present in prenatal vitamins] have

little effect on circulating 25-OH-D g

Lactation and Vitamin D

† With a supplement of 400 IU, vitamin D content of h man milk ranges from

content of human milk ranges from

<25 to 78 IU/L

† Exclusively breast fed infants without additional vitamin D are at risk

additional vitamin D are at risk

† Universal supplementation of the mother not

recommended

Lactation and Vitamin D

† Vitamin D deficiency can occur early in life, especiall in infants of deficient mothers

especially in infants of deficient mothers

† 25 OH-D concentrations are low in unsupplemented breastfed infants

† Amount of sunshine exposure is not easy to

† Amount of sunshine exposure is not easy to determine and not recommended

† Serum concentrations >50 nmol/L of 25-OH-D

maintained by 400 IU per day y p y

Supplementation

† 400 IU per day starting in the first few days through childhood

through childhood

† Formula fed infants who ingest a quart of

f l d ill hi 400 IU/d

formula per day will achieve 400 IU/d

† Vitamin D fortified milk after weaning

† Adolescents should receive same supplement if not consuming fortified cereals and eggs

if not consuming fortified cereals and eggs

† Serum conc of 25-OH-D >50nmol/L

Definitions

† Estimated Average Requirement [EAR]

„

Meet requirement of half the healthy individuals in a life stage and gender

„

Meet requirement of half the healthy individuals in a life stage and gender group

† Recommended Dietary Allowance [RDA]

† Recommended Dietary Allowance [RDA]

„

Meet requirement of nearly all [97.5%]

† Adequate Intake [AI]

† Adequate Intake [AI]

„

When EAR or RDA cannot be determined, approximations of observed mean nutrient intakes is set as AI

† Tolerable Upper Intake Level [UL]

„

Highest level of intake that is likely to pose no risk

DRI for Ca and vitamin D

Calcium Calcium Calcium Vit D Vit D Vit D Life Stage EAR, mg/d RDA,

/d

Upper l l

EAR, IU/d RDA, IU/d

Upper l l IU/d mg/d level,

mg/d

IU/d level, IU/d

0-6 mo * * 1000 ** ** 1000

6-12 mo * * 1500 ** ** 1500

1 3 yo 500 700 2500 400 600 2500

1-3 yo 500 700 2500 400 600 2500

DRI

† * for infants

Ad I k f l i

„ Adequate Intake of calcium:

† 200 mg/d 0-6 mo

† 260 mg/d 6-12 mo

† ** for infants

„ Adequate Intake of vitamin D

† 400 IU/d 0-6 mo

† 400 IU/d 0-6 mo

† 400 IU/d 6-12 mo

DRI

Calcium Calcium Calcium Vit D Vit D Vit D EAR, RDA, , ULI, mg/d EAR, IU/d RDA, ULI, IU/d mg/d

, mg/d

, g , ,

IU/d

,

9-13 y 1100 1300 3000 400 600 4000

14-18 y 1100 1300 3000 400 600 4000

14-18y, 1100 1300 3000 400 600 4000

14 18y, preg/lact

1100 1300 3000 400 600 4000

19-50 y, preg/lact

800 1000 2500 400 600 4000

preg/lact

Summary

† DRIs are intended to serve as a guide for good n trition

nutrition

† Basis for the development of nutrient guidelines in the US and Canada

† Vitamin D issue is more complicated

† Vitamin D issue is more complicated

„ Dietary vitamin D plus synthesis in skin

„ Sunlight exposure varies

„ Committee assumed minimum sun exposure p

Current Intake

† Calcium may remain a nutrient of concern especiall in girls 9 18

especially in girls 9-18 y

† Menopausal women taking supplements may be getting too much calcium

† For vitamin D average total intake is below

† For vitamin D, average total intake is below the median requirement

† Average levels of vitamin D are >20 ng/mL

Summary

† As people take more supplements and eat more fortified foods high intakes of calci m more fortified foods, high intakes of calcium and vitamin D may occur

† Kidney stones with too much calcium

† >10 000IU vitamin D/d kidney and tissue

† >10,000IU vitamin D/d kidney and tissue damage

† Other benefits from Vitamin D except bone

health are not based on evidence

Summary

† To prevent rickets and Vitamin D deficiency in health infants children and adolescents in healthy infants, children, and adolescents

„ Vitamin D intake of at least 400 IU/d is

recommended

Summary

† Breastfed and partially breastfed infants should be supplemented with 400-600 IU/d of Vitamin D

supplemented with 400-600 IU/d of Vitamin D beginning in the first few days of life

† Continue supplementation until infant is weaned to

† Continue supplementation until infant is weaned to at least 1L/day or 1 qt/day of Vitamin D-fortified formula or whole milk

formula or whole milk

† All nonbreastfed infants, as well as older children

h i i 1000 L/d f Vi i D

who are ingesting <1000 mL/d of Vitamin D-

fortified-formula or milk, should receive a vitamin D l f 400 600 IU/d

supplement of 400-600 IU/d

Summary

† Adolescents need 400 IU per day through fortified milk and fortified foods

fortified milk and fortified foods

† Serum 25-OH-D should be > 50 nmol/L

† Children with malabsorption syndromes or infants receiving anti seizure medication may infants receiving anti-seizure medication may require additional doses of Vitamin D

† Pediatrician should strive to make vitamin D

supplements readily available to all children pp y