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



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Vitamin D Jatinder Bhatia, MD, FAAP

Question I A vitamin D deficient mother will give birth to an infant with Vit D deficiency A. True B. False Answer A

Question II Human breast milk has adequate amounts of Vitamin D to sustain stain the bone health of a healthy term infant Atrue A. B. False Answer: B

Question III Chronic Vitamin D deficiency presents with A. Decreased bone mineralization B. Hypomagnesemia C. Seizures Answer: A

Causes Inadequate exposure to sunlight Malabsorption lb [intestinal i resection, short bowel syndrome, cystic fibrosis] Minimal amounts in breast milk Mdi Medications [dilantin, phenobarbital, bitl rifampin]

Frequency Highest among elderly, 60% of nursing home residents, 57% hospitalized patients Healthy young adults: nearly 2/3 of young adults are vitamin D deficient by end of winter in Boston Canada and Europe similar to US Significantly higher prevalence of deficiency in middle eastern countries, women>men

Vitamin D Deficiency Rickets Extreme vitamin i D deficiency i 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 respiratory infections during infancy

Vitamin D Deficiency Rickets is preventable Cases of rickets due to vitamin D deficiency and decreased exposure to sunlight continue to be reported in the US and other western countries Exclusive breast feeding and darker skin pigmentation i Not limited to infancy and early childhood, teens reported

Vitamin D Deficiency Two types of presentations [Arch Dis Child 2004; 89:781-784] 784] Symptomatic hypocalcemia occurring during periods of rapid growth Chronic: rickets and/or decreased bone mineralization; normocalcemia or asymptomatic ti hypocalcemia

Vitamin D Two forms D 2, ergocalciferol, synthesized by plants D 3, cholecalciferol, synthesized by mammals D 3 main source for humans Synthesis in the skin, UV-B 290-315nm converts 7- dehydrocholesterol into previtamin D3 Previtamin D 3 transformed to D 3 >>binds with D-binding protein >> liver>>25-hydroxyvitamin D 25-OH-D undergoes another hydroxylation in the kidney >>1,25- 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 throughout childhood may reduce risk of osteoporosis, long-latency disease processes in adults Vitamin i D as a natural ingredient in foods is limited Fatty fish, fish oils, liver, egg yolks of D supplemented chickens

Vitamin D Innate immunity Prevention of finfections i Auto-immune diseases [multiple sclerosis, rheumatoid arthritis] Breast, ovarian, prostate, t colorectal l cancers Type-2 diabetes mellitus 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 Increased Alk Phos Stage III: hypocalcemia Hypophosphatemia Increased alk phos Bone dimineralization

Clinical Signs Dietary Ca absorption decreases from 30-40% to 10-15% 15% with D deficiency Low 25-OH-D >>PTH in older infants, children and teens>>mobilizes calcium from bone>>reduction in bone mass>>fractures Rickets Enlargement of skull, joints, rib cage Osteomalacia, osteopenia

Metabolic Bone Disease

Recommended Daily Intake Initially, based on data from US, Norway and China, 200IU/d was recommended This dose prevented physical signs of deficiency and 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 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 with darker skin Skin pigmentation, pg body mass, latitude and season, cloud cover, air pollution, clothing and sunscreen US: average of 93% of time spent indoors

Sunlight Exposure CDC, AAP, American Cancer Society Risks for various skin cancers Age may be more important than total sunlight exposure over a lifetime Infants < 6 months: no direct sunlight Protective clothing and sunscreen Vitamin D supplementation

Pregnancy, Vitamin D and the Fetus Maternal deficiency can occur with restricted vitamin D intake and lack of sun exposure Data suggest that doses >1000 IU per day of vitamin D are necessary to achieve 25-OH-D concentrations > 50 nmol/l in pregnant women Vit D deficient mother will give birth to a Vit D deficient neonate

Pregnancy, Vitamin D and the Fetus Adequate nutritional vitamin D status important during pregnancy Association with better weight gain, correlation with head circumference 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

Lactation and Vitamin D With a supplement of 400 IU, vitamin D content of human milk ranges from <25 to 78 IU/L Exclusively breast fed infants without 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, especially in infants of deficient mothers 25 OH-D concentrations are low in unsupplemented breastfed infants 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

Supplementation 400 IU per day starting in the first few days through childhood Formula fed infants who ingest a quart of 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 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 group Recommended Dietary Allowance [RDA] Meet requirement of nearly all [97.5%] 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, mg/d Upper level, l mg/d EAR, IU/d RDA, IU/d 0-6 mo * * 1000 ** ** 1000 6-12 mo * * 1500 ** ** 1500 1-3 yo 500 700 2500 400 600 2500 Upper level, l IU/d

DRI * for infants 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 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 IU/d 9-13 y 1100 1300 3000 400 600 4000 14-18 y 1100 1300 3000 400 600 4000 14-18y, 18y, 1100 1300 3000 400 600 4000 preg/lact 19-50 y, preg/lact 800 1000 2500 400 600 4000

Summary DRIs are intended to serve as a guide for good nutrition Basis for the development of nutrient guidelines in the US and Canada Vitamin D issue is more complicated Dietary vitamin D plus synthesis in skin Sunlight exposure varies Committee assumed minimum sun exposure

Current Intake Calcium may remain a nutrient of concern especially in girls 9-18 y Menopausal women taking supplements may be getting too much calcium 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 calcium and vitamin D may occur Kidney stones with too much calcium >10,000IU 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 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 beginning in the first few days of life Continue supplementation until infant is weaned to at least 1L/day or 1 qt/day of Vitamin D-fortified formula or whole milk All nonbreastfed infants, as well as older children who are ingesting i <1000 ml/d of Vitamin i D- fortified-formula or milk, should receive a vitamin D supplement of 400-600 IU/d

Summary Adolescents need 400 IU per day through 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 require additional doses of Vitamin D Pediatrician should strive to make vitamin D supplements readily available to all children