nutrient needs: part 2 vitamin k vitamin d calcium and phosphorus iron zinc b-12 flouride

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)

• 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

Term Age and Incidence

Symptoms

Early vitamin K deficiency bleeding (VKDB)*

First week of life: Unexpected bleeding in previously healthy-appearing neonates

Late VKDB 2-12 weeks of age

unexpected bleeding attributable to severe vitamin K deficiency

* 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


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.


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

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 dependent on 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

Calcium and Phosphorus

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

CalciumAge DRI mg/d

Birth-6 months 210

7-12 months 270

1-3 years 500

4-8 years 800

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

Iron Deficiency Anemia

• Impact on social, neurobehavioral and sleep– Peirano et al: Sleep and Neurofunction Throughout Child

development: Lasting Effects of Early Iron Deficiency J Ped Gastroenterology and Nutr 2009 48:S8-S15

– Lozoff et al: Dose-Response Relationships between Iron deficiency with or without anemia and Infant Social-emotional Behavior J Pediatr 2008 152:696-702

Peirano

• Slower neurotransmission in auditory and visual systems

• Different motor activity patterning sleep-waking and sleep state organization

• Alterations in behavioral and cognitive function

Lozoff

• N=77• “Infant social-emotional behavior appears to

be adversely affected by iron deficiency with or without anemia”– Shyness, orientation engagement, soothability

Carter et al: Iron Deficiency Anemia and Cognitive Function in Infancy: Pediatrics 2010 126;2427-e434

• N= 87 (28 IDA, 49 no anemia)• Methods: at 9 and 12 months series of

cognitive, intellegent and behavioral tests administered (Fagan test of infant intellegence (FTII), Emotionality, Activity and Sociability Temperment Survey, and Behavior Rating Scale (BRS))

Carter et al: Iron Deficiency Anemia and Cognitive Function in Infancy: Pediatrics 2010 126;2427-e434

• Results– Sociodemographic background similar between 2

groups– IDA infants less likely to exhibit object

permanence, less novelty preference on the FTII, lower BRS scores, and decrease engagement/orientation, described as “shyer”

Iron Deficiency

• Among children in developing world, iron is the most common single nutrient deficiency

• No national statistics for prevalence of ID or IDA < 12 months

Iron Deficiency in Breastfeeding

• At 4 to 5 months prevalence of low iron stores in exclusively breastfed infants is 6 - 20%.

• A higher rate (20%-30%) of iron deficiency has been reported in breastfed infants who were not exclusively breastfed

• The effect of iron obtained from formula or beikost supplementation on the iron status of the breastfed infant remains largely unknown and needs further study.

Iron Deficiency Prevalence at 9 Months

1.1 mg iron per L plussupplemental foods

28-38%

12-15 mg iron per L 0.6%

Iron Fortification of Formula

• “The increased use of iron-fortified infant formulas from the early 1970s to the late 1980s has been a major public health policy success. During the early 1970s, formulas were fortified with 10 mg/L to 12 mg/L of iron in contrast with nonfortified formulas that contained less than 2 mg/L of iron. The rate of iron-deficiency anemia dropped dramatically during that time from more than 20% to less than 3%.”

ID and IDA 12-35 Months NHANES 2002

Population ID (%) IDA (%)General US 9.2 2.1Above poverty 8.9 2.2Below poverty 8.6 2.3Enrolled in WIC

10.7 3.2

Mexican American

13.9 0.9

Other ethnicity 15.2 4.4

Iron

• Iron absorption from soy formulas is less• Greater bioavailabilty of iron in breastmilk

Percent Reported Absorbed

Study

Human Milk 48%

Hallberg et al

Human Milk – in 5 to 7 month olds who are also eating solid foods.

21% Abrams et al

Iron Fortified Cow’s milk based Formula

6.7% Hurrel et al

Infant Cereals 4 to 5%

Fomon et al

Iron Absorption In Infancy

Foman on Iron - 1998

• Proposes that breastfed infants should have supplemental iron (7 mg elemental) starting at 2 weeks.

• Rational:– some exclusively breastfed infants will have low iron stores

or iron deficiency anemia– Iron content of breastmilk falls over time– animal models indicate that deficits due to Fe deficiency in

infants may not be recovered when deficiency is corrected.

AAP recommendations for Dx and prevention of ID and IDA:2010Pediatrics 2010 126 #5

• Birth-6 months: 0.27 mg/d– Assuming average content Breastmilk 0.35 mg/L

and average intake 0.78 L/day– Noted variability of iron content of breastmilk,

high risk populations (IUGR, LGA associate with maternal IDM, maternal anemia, Preterm birth)


• 7-12 months: 11 mg/d– Factorial approach: iron loss, iron needed for

increased blood volume, tissue mass, and stores– Noted that there isn’t a sudden increase in needs

from 6 to 7 months.


• Diagnosis:– Iron status is a continuum with IDA at one end of

the spectrum– No single measurement is currently available to

characterize iron status– HgB limitations include specificity and sensitivity.

Identifies anemia but not necessarily ID or IDA


• Term, healthy infants have sufficient Fe to 4 months. • Formula fed: Fe needs met by standard infant formula with 12

mg/dl and introduction of complementary foods after 4-6 months. Whole milk shouldn’t be used < 12 months

• Breastfed: Exclusively breastfed infants are a increasing risk of ID >4 months and should be supplemented with 1 mg/kg/d oral Fe until appropriate complimentary food are introduced


• 6-12 months– 11 mg/d– Use complimentary foods with higher iron

content. Liquid supplement may be needed to augment complimentary foods


• Univeral screening should be done at 12 months with Hgb and risk determination

• Additional screening can be preformed at any time if there is a risk of ID/IDA including inadequate intake

Iron: DRIAge Iron mg/d

Birth-6 months 0.27

7-12 months 11

1-3 years 7

4-8 years 10

Food sources of IronFood Measure Iron (mg)

Iron fortified formula 8 oz 2.9

Infant Cereal (rice) 1TB 1.7

Strained meats with vegetable 2 Tb 0.1

Strained beef 2 TB 0.2

meats 2 TB 1.2

egg 1 0.7

Peanut butter 1 TB 0.3

Bread white 1 slice 0.2

Enriched macaroni cooked ¼ cup 0.5

vegetables ¼ cup 0.2

fruits ¼ cup 0.1

cheerios ½ cup 1.2

Rice Chex ½ cup 1

Other Causes of Anemia

• Jones et al Hidden Threats: Lead Poisoning From Unusual Sources Pediatrics 1999 104(1223-1225)

• Jones et al Trends in Blood Lead Levels and Blood Lead Testing Among US Children Aged 1-5 years Pediatrics 2009 123 (e376-e385)

Iron-Lead Interactions

• IDA increases intestinal lead absorbtion• Epidemiologic association between IDA and

increased lead concentrations• Primary prevention of IDA may contribute to

prevention of lead poisoning• IDA also decreases the efficiency of chelation

therapy for lead poisoning.• Effect of iron supplementation on iron replete

children with lead poisoning is not know

Zinc

• Function: metalloenzymes associated with CHO and energy metabolism, protein catabolism and synthesis, nucleic acid synthesis, and heme biosynthesis. Other zinc dependent enzymes include erythrocyte carbonic anhydrase, alkaline phosphatase, DNA and RNA polymerases. Through its role in superoxide dismutase enzyme systems, Zinc acts in stabilzing cell membranes and protecting them from lipid peroxidation. Zinc is also involved in protein and collagen synthesis

Zinc• Concentration in colostrum is high, but

concentration rapidly declines over 1st year. • Reports of subclinical zinc deficiency in

growing preterm infant fed human milk– * continued post-discharge

Zinc

• Globally, zinc deficiency is widespread in infants and young children in developing countries, being a major cause of morbidity and mortality, and of impaired growth.– Diarrhea, pneumonia associated morbidities– Due to zinc dependent host defense mechanisms

(T and B cell functions)

Zinc, Folate, Vitamin EAge Zinc mg/d Folate mcg/d Vitamin E mg/d

Birth-6 months 2 65 4

7-12 months 3 80 5

1-3 years 3 150 6

4-8 years 5 200 7

B-12

• B-12 concentration in breastmilk may be influenced by maternal diet.

• Milk from lactating mothers following a strict vegan diet may provide inadequate vitamin B-12 to their infants.

• B-12 deficiency has been reported in infants breast-fed by mothers with pernicious anemia.

Vitamin B12

• No reports of overt toxicity• Overt deficiency

documented among infants and children who are fed no animal foods & are not supplemented

• DRI: (mcg.d)– B-6 months: 0.4– 7-12 months: 0.5– 1-3 years: 0.9– 4-8 years: 1.2

• 15 mo old infant• Breastmilk only, 10 x/day• Appeared well-nourished• Refused solids• Demonstrated

developmental delay• < blood B12, folate, Fe

Vitamin B12

• Mother, appeared well-nourished

• taking extra Vit A, 100ug B12, 3-4000mg Vit C/day

• Reluctant to D/C breastfeeding

• Worried re: intro of solids, allergies

• Infant– supplemented

• folic acid, iron

– 1000 ugB12 IM– PolyViFlor

Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional Vitamin B-12 deficiency

• Eur J Paed Neurol Nov 2010 14(16) 488-95• 40 Breast fed infants with B-12 deficiency (17

severe, 23 mild• Maternal B-12 satus major contributing factor• Symptoms: FTT (48%), DD (38%),

microcephaly (23%), anemia (63%)

Fluoride

• Fluoride and dental caries– At beginning of 20th century dental caries was

common with extraction only treatment available– Failure to meet minimum standards of 6 opposing

teeth was common cause of rejection from military service in WWI and WWII

Fluoride

• 1901 Dr. Frederick S Mckay noted mottled teeth (fluorosis) in practice in Colo Springs Colo that were resistent to decay

• 1909 Dr. FC Robertson noted same mottling in his area of practice after a new well dug– Believed was due to something in the water

Fluoride

• 1945 study was conducted in 4 city pairs (Michigan, NY, Illinois, Ontario)

• Followed 13-15 years• 50-60% reduction in dental caries

Fluoride

• Proposed mode of action– Promotes remineralization of areas of cariogenic

lesions– Increases resistance to acid demineralization– Interferes with formation and function of plaque

forming microorganisms– Improves tooth morphology

Fluoride

• Concerns– Excess– Fluorosis– Cancer– other

Fluoride

• Fluoride Recommendations were changed in 1994 due to concern about fluorosis.

• Breast milk has a very low fluoride content. • Fluoride content of commercial formulas has been

reduced to about 0.2 to 0.3 mg per liter to reflect concern about fluorosis.

• Formulas mixed with water will reflect the fluoride content of the water supply. Fluorosis is likely to develop with intakes of 0.1 mg/kg or more.

Fluoride, cont.

• Fluoride adequacy should be assessed when infants are 6 months old.

• Dietary fluoride supplements are recommended for those infants who have low fluoride intakes.

Fluoride Supplementation Schedule Age Fluoride Concentration in Local

Water Supply, ppm < 0.3 0.3-0.6 >0.6 6 mo. to 3 y 0.25 0.00 0.00 3-6 y 0.50 0.25 0.00 6 y to at least 16 y

1.00 0.50 0.00

American Dental Association, American Academy of Pediatrics, American Academy of Pediatric Dentistry, 1994.

Fluoride

• To prevent fluorosis, tolerable upper limit (UL) has been set at 0.7 mg/d B-6 months, and 0.9 mg/d 7-12 months

• AAP– Not recommended < 6 months– 0.25 mg/d after 6 months if water contains < 0.3 ppm)– After tooth eruption: fluoridated water several

times/day (BF) or prepare formula with water with fluoridated water (<0.3 mg/L)

–

Early Childhood Caries

• AKA Baby Bottle Tooth Decay

• Rampant infant caries that develop between one and three years of age

Early Childhood Caries: Etiology

• Bacterial fermentation of cho in the mouth produces acids that demineralize tooth structure

• Infectious and transmissible disease that usually involves mutans streptococci

• MS is 50% of total flora in dental plaque of infants with caries, 1% in caries free infants

Early Childhood Caries: Etiology

• Sleeping with a bottle enhances colonization and proliferation of MS

• Mothers are primary source of infection• Mothers with high MS usually need extensive

dental treatment

Early Childhood Caries: Pathogenesis

• Rapid progression• Primary maxillary incisors develop white spot

lesions• Decalcified lesions advance to frank caries

within 6 - 12 months because enamel layer on new teeth is thin

• May progress to upper primary molars

Early Childhood Caries: Prevalence

• US overall - 5%• 53% American Indian/Alaska Native children• 30% of Mexican American farmworkers

children in Washington State• Water fluoridation is protective• Associated with sleep problems & later

weaning

Early Childhood Caries: Cost

• $1,000 - $3,000 for repair• Increased risk of developing new lesions in

primary and permanent teeth

Early Childhood Caries: Prevention

• Anticipatory Guidance:– importance of primary teeth– early use of cup– bottles in bed– use of pacifiers and soft toys as sleep aides

Early Childhood Caries: Prevention

• Chemotheraputic agents: fluoride varnishes and supplements, chlorhexidene mouthwashes for mothers with high MS counts

• Community education: training health providers and the public for early detection

nutrient needs: part 2 vitamin k vitamin d calcium and phosphorus iron zinc b-12 flouride

Documents

administration of vitamin

severe vitamin

births im vitamin

late onset vitamin

infants requirement

newborn slide

vitamin d calcium

late slide