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Nutrient Needs: Part 2. Vitamin K Vitamin D Calcium and Phosphorus Iron Zinc B-12 Flouride. Vitamin K. Vitamin K. 2 forms: K1 or phylloquinone (plant form) and K2 (synthesized by bacteria)
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Nutrient Needs: Part 2 • Vitamin K • Vitamin D • Calcium and Phosphorus • Iron • Zinc • B-12 • Flouride
Vitamin K • 2 forms: K1 or phylloquinone (plant form) and K2 (synthesized by bacteria) • Function: cofactor in metabolic conversion of precursors of Vitamin K dependent proteins to active form ( eg: prothrombins, osteocalcin)
Vitamin K • Lack of specific information regarding an infant’s requirement • Vitamin K concentration of breastmilk is low and for the breastfeeding infant a deficiency state has been described • No “gold standard” available
Vitamin K deficiency: Haemorrhagic disease of newborn • First used in 1894 to describe bleeding in the newborn not due to trauma or haemophilia • Current Terminology: • VKDB: vitamin K deficiency bleeding • EVKDB: early • LVKDB: late
Vitamin K Deficiency- definitions – AAP, 2003 * Formerly known as classic hemorrhagic disease of the newborn
Incidence of VKDB • Early: 0.25%–1.7% incidence • Late: • No vitamin K prophylaxis: 4.4 to 7.2 per 100,000 births • Single oral vitamin K prophylaxis:1.4 to 6.4 per 100 000 births • IM vitamin K prophylaxis: 0 • Oral vitamin K has effect similar to IM in preventing early VKDB, but not in preventing late VKDB
Vitamin K • DRI for infants 2-2.5 ug/day • Formula provides 7-9 ug/kg/d • BM contains < 10 ug/L • Hemorrhagic disease of the Newborn…Vitamin K deficiency • Prophylaxis: 1 mg Vitamin K IM for all newborn infants
Controversies Concerning Vitamin K and the Newborn: AAP Policy Statement, 2003
Vitamin K Controversy • Adequacy of BM • Maternal Diet and Vitamin K content of BM • ? Significance/prevalence of hemorrhagic disease of newborn • IM injections of all newborns
Danielson et al Arch Dis Child 2004 89:F546-550 • Late onset vitamin K deficient bleeding in infants who did not receive prophylactic vitamin K at birth in Hanoi province • Incidence: 116 per 100,000 births • Higher in rural areas • 9% mortality • 42% impaired neurodevelopmental status at discharge in survivors
Incidence • Netherlands 2005: 3.2 per 100,000 births • Canada 2004: 0.45 per 100,000 births • Conclude low incidence associated with current practice of prophylactic Vitamin K at birth
Closing the Loophole:Midwives and the Administration of Vitamin K in the Neonate Adame and Carpenter J Pediatr 2009 154:769-771 Case Report of a previously healthy, exclusively breastfed 6 week old infant delivered by a midwife on the south Texas border. Did not receive Vitamin K at birth. Admitted with severe intracranial hemorrhage, cooagulopathy, and seizures, unresponsive, pupils fixed and dialated
Brousson and Klien, Controversies surrounding the administration of vitamin K to newborns; a review. CMAJ. 154(3):307-315, February 1, 1996. • Study selection: Six controlled trials met the selection criteria: a minimum 4-week follow-up period, a minimum of 60 subjects and a comparison of oral and intramuscular administration or of regimens of single and multiple doses taken orally. All retrospective case reviews were evaluated. Because of its thoroughness, the authors selected a meta-analysis of almost all cases involving patients more than 7 days old published from 1967 to 1992. Only five studies that concerned safety were found, and all of these were reviewed
Brousson and Klien, Controversies surrounding the administration of vitamin K to newborns; a review. CMAJ. 154(3):307-315, February 1, 1996. • Data synthesis: Vitamin K (1 mg, administered intramuscularly) is currently the most effective method of preventing HDNB. The previously reported relation between intramuscular administration of vitamin K and childhood cancer has not been substantiated. An oral regimen (three doses of 1 to 2 mg, the first given at the first feeding, the second at 2 to 4 weeks and the third at 8 weeks) may be an acceptable alternative but needs further testing in largeclinical trials.
Brousson and Klien, Controversies surrounding the administration of vitamin K to newborns; a review. CMAJ. 154(3):307-315, February 1, 1996 • Conclusion: There is no compelling evidence to alter the current practice of administering vitamin K intramuscularly to newborns.
Cochran Prophylactic Vitamin K for preventing haemorrhagic disease in newborn infants Vitamin K deficiency can cause bleeding in an infant in the first weeks of life. This is known as Haemorrhagic Disease of the Newborn (HDN) or Vitamin K Deficiency Bleeding (VKDB).
Cochran • The risk of developing vitamin K deficiency is higher for the breastfed infant because breast milk contains lower amounts of vitamin K than formula milk or cow's milk
Cochran • In different parts of the world, different methods of vitamin K prophylaxis are practiced.
Cochran • Oral Doses: • The main disadvantages are that the absorption is not certain and can be adversely affected by vomiting or regurgitation. If multiple doses are prescribed the compliance can be a problem
Cochran • I.M. prophylaxis is more invasive than oral prophylaxis and can cause a muscular haematoma. Since Golding et al reported an increased risk of developing childhood cancer after parenteral vitamin K prophylaxis (Golding 1990 and 1992) this has been a reason for concern .
Cochrane Conclusions, 2000 • A single dose (1.0 mg) of intramuscular vitamin K after birth is effective in the prevention of classic HDN. • Either intramuscular or oral (1.0 mg) vitamin K prophylaxis improves biochemical indices of coagulation status at 1-7 days. • Neither intramuscular nor oral vitamin K has been tested in randomized trials with respect to effect on late HDN. • Oral vitamin K, either single or multiple dose, has not been tested in randomized trials for its effect on either classic or late HDN.
Oral Supplementation with Vitamin K • Increase in reports of late VKDB • Single oral dose does not provide sustained elevations in serum Vitamin K to prevent late bleeding • Multidose regimen (1-2 mg given 3X over first 3 months) has been used in some countries • Some studies report efficacy • Also, reports of treatment failure (eg Germany, Australia, Sweden) • Disadvantages: reliance on compliance, increased cost, unreliable infant intake/feeding • AAP recommends contininuation of IM prophylaxis
AAP Recommendations: Pediatrics:Vol112#1 July 2003 1. Vitamin K1 should be given to all newborns as a single, intramuscular dose of 0.5 to 1 mg. 2. Further research on the efficacy, safety, and bioavailability of oral formulations of vitamin K is warranted.
AAP Recommendations 3. Health care professionals should promote awareness among families of the risks of late VKDB associated with inadequate vitamin K prophylaxis from current oral dosage regimens, particularly for newborns who are breastfed exclusively 4. Earlier concern regarding a possible causal association between IM vitamin K and childhood cancer has not been substantiated
Vitamin D • Role • Source • Dietary • sunlight • Deficiency • Rickets
Role • Enhances intestinal absorption of Ca • Increase tubular resorption of Ph • Mediation of recycling of Ca and Ph for bone growth and remodeling • Sterol hormone • Deficiency: Rickets
Role • Extraskeletal effects of Vitamin D • Modulates B and T Lymphocyte fx and deficiency may be associated with autoimmune diseases (diabetes, MS associations) • Regulation of cell growth (assoc with breast, prostrate, and colon cancer)
Prevalence • Thought to be disease of past (prior to 1960’s) • Disappeared secondary to recognition of role of sunlight, fortification of milk, use of multivitamins, AAPCON recommendation for 400 IU supplementation of infants
Prevalence • Increased incidence and case reports 1970’2 • No national data in US • Georgia 1997-99: 9 per million hospitalized children • National Hospital Discharge Survey: 9 per million • Pediatric Research in Office Setting (AAP):23-32 hospitalized cases reported 1999-2000
Prevalence • Literature Review • 13 articles published between 1996-2001 • 122 case reports
Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake PEDIATRICS Vol. 111 No. 4 April 2003, pp. 908-910
Vitamin D and Sunlight • Vitamin D requirements are dependenton the amount of exposure to sunlight. • Dermatologists recommend caution with sun exposure. • Sunscreens markedly decrease vitamin D production in the skin • Decreased sunlight exposure occurs during the winter and other seasons and when sunlight is attenuated by clouds, air pollution, or the environment • AAP recommends against exposing infants < 6 months to direct sun
Breastfeeding and Vitamin D • Breastmilk has < 25 IU/L Recommended adequate intake can not be met with breastmilk alone • Formerly stated that needs could be met with sun exposure, but now, due to cancer concerns recommend against this
Vitamin D Recommendations • Before 2003 AAP recommended 10 mg (400 IU) per day for breastfeed infants • 2003: American Academy of Pediatrics recommends supplements of 5 mg (200 IU) per day for all infants as recommended in DRIs. • 10/14/2008: AAP updates guidelines for vitamin D intake for infants, children, and teens to be published in Nov 5th ed Pediatrics • 400 IU per day intake of vitamin D beginning in first few days of life
Formulas • if an infant is ingesting at least 500 mL per day of formula (vitamin D concentration of 400 IU/L), he or she will receive the recommended vitamin D intake of 200 IU per day. • If intake is less than 500 ml recommend additional supplement of vitamin D
Summary of AAP Recommendations • All breastfed infants unless they are weaned to at least 500 mL per day of vitamin D-fortified formula or milk. • All nonbreastfed infants who are ingesting less than 500 mL per day of vitamin D-fortified formula or milk. • Children and adolescents who do not get regular sunlight exposure, do not ingest at least 500 mL per day of vitamin D-fortified milk, or do not take a daily multivitamin supplement containing at least 200 IU of vitamin D.
AAP Recommendations for Vitamin D • 2008 • Intake of 400 IU beginning in first few days of life • Supplement breastfed, partially breastfed, infants and children consuming less than 1 liter formula or vitamin D fortified whole milk • Wagner et al: Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents: Pediatrics 2008;122;1142-1152
Vitamin D • DRI: B-6 months 200 IU, 7-12 months 250 IU • UL: 1000 IU
Basis of recommendations • Previous RDA of 400-800 mg/d of Ca was based on formula feeding with 25-30% retention • Breastfed infants retain 2/3 of their Ca intake from breastmilk
Hot off the Presses! • FNB IOM recommends Calcium intake • B-6 months: 200 mg/d • 7-12 months: 260 mg/d • 1-3 years of age: 700 mg/d • 4-8 years of age: 1000 mg/d
Calcium/Phosphorus content of typical Infant feedings: (mg/dl) • Breastmilk: • 28/14 • Standard Infant Formula • 49/38
Iron • Function • Source • Formula, breast milk, other foods • Bioavailability: • Breast milk • Soy formula • Deficiency • Anemia
Anemia • Anemia (low Hct, Hgb: not specific for iron deficiency) Causes: • Inadequate iron in diet • Loss • GI bleeding, cows milk proteins, infectious agents • Other • Genetics • Lead • Other nutrients
Iron • Biological function • Oxygen transport primarily in hemoglobin • Component of other proteins including cytochrome a, b, c, and cytochrome oxidase essential for electron transport and cellular energetics
Iron deficiency (ID and IDA) • Anemia: Hgb <11 g/dl 12-36 months • Iron deficiency Anemia (IDA): anemia due to iron deficiency • Iron deficiency: Insufficient iron to maintain normal physiologic functions leading to decrease in iron stores as measured by serum ferritin with or without IDA
Association between ID and IDA and neurobehavioral development • Lozoff • McCann and Ames • Cochrane review • Carter • Recent sleep studies