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  1. Nutrient Needs: Part 2 • Vitamin K • Vitamin D • Calcium and Phosphorus • Iron • Zinc • B-12 • Flouride

  2. Vitamin K

  3. 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)

  4. 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

  5. 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

  6. Vitamin K Deficiency- definitions – AAP, 2003 * Formerly known as classic hemorrhagic disease of the newborn

  7. 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

  8. 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

  9. Controversies Concerning Vitamin K and the Newborn: AAP Policy Statement, 2003

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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).

  18. 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

  19. Cochran • In different parts of the world, different methods of vitamin K prophylaxis are practiced.

  20. 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

  21. 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 .

  22. 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.

  23. 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

  24. 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.

  25. 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

  26. Vitamin D

  27. Vitamin D • Role • Source • Dietary • sunlight • Deficiency • Rickets

  28. 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

  29. 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)

  30. 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

  31. 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

  32. Prevalence • Literature Review • 13 articles published between 1996-2001 • 122 case reports

  33. Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake PEDIATRICS Vol. 111 No. 4 April 2003, pp. 908-910

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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.

  39. 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

  40. Vitamin D • DRI: B-6 months 200 IU, 7-12 months 250 IU • UL: 1000 IU

  41. Calcium and Phosphorus

  42. 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

  43. Calcium

  44. 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

  45. Calcium/Phosphorus content of typical Infant feedings: (mg/dl) • Breastmilk: • 28/14 • Standard Infant Formula • 49/38

  46. Iron • Function • Source • Formula, breast milk, other foods • Bioavailability: • Breast milk • Soy formula • Deficiency • Anemia

  47. 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

  48. 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

  49. 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

  50. Association between ID and IDA and neurobehavioral development • Lozoff • McCann and Ames • Cochrane review • Carter • Recent sleep studies