Infantnutrient needs

Basis/ApproachPublic health vs individualrecommendations, guidelines, education

Specific nutrientswaterenergyproteinfatty acidsvitamin KVitamin DIronFluoride

Basis of recommendations

• Growth and development

• Physiology– GI– Renal

• Programming• Public health vs

individual

• Optimize growth and development

• Prevent deficiencies• Safety• Prevention of chronic

illness and optimize health through life cycle

Approaches to Estimating Nutrient Requirements

• Direct experimental evidence (ie protein and amino acids)

• Extrapolation from experimental evidence relating to human subjects of other age groups or animal models– ie thiamin--related to energy intake .3-.5 mg/1000 kcal

• Breast milk as gold standard (average [] X usual intake)• Metabolic balance studies (ie protein, minerals)• Clinical Observation (eg: manufacturing errors B6, Cl)• Factorial approach• Population studies

Challenges

• Strength of Evidence• Individual vs population

– Public health approach– Individual genetics– Maternal-infant dyad

• In utero endowment• Beliefs, values, choices• Relationship/nurture

– Environmental factors

Public health vs individual

• Prevalence of nutrient deficiencies• Balance incidence, burden, and treatment

– Eg: Vitamin K and hemorrhagic disease of newborn

• Prevalence and evidence of chronic conditions associated with dietary practices

• Etiology of nutrient deficiencies and/or chronic conditions– Eg: allergy, obesity, anemia, dental caries,…

– Genetics– Adaptation– Environment– Behavior/activity– Choices, access,

resources– other

Individual Requirements

1940’s

• Rickets (D)

• Pellagra (Niacin)

• Scurvy (C)

• Beriberi (Thiamin)

• Xeropthalmia (A)

• Goiter (Iodine)

United Nations 5th report on World Nutrition: March 2004

Prevalence (%) 1990 2005

underweight 35.2 26.5

Iodine deficiency 35.2

• Vitamin A deficiency– 140 million preschoolers– 7 million pregnant women

• Iron Deficiency– One of most prevalent– 4-5 billion affected

United Nations 5th report on World Nutrition: March 2004

• Reports in US of PEM, Rickets, Zinc deficiencies

Causes

Nutrition - Disease

Access

Food

Health Care

Environment

Economics

Education

Programming by Early Diet

• Nutrient composition in early diet may have long term effects on GI function metabolism and health

• Animal models show that glucose and amino acid transport activities are programmed by composition of early diet

• Animals weaned onto high CHO diet have higher rates of glucose absorption as adults compared to those weaned on high protein diet

• Barker Hypothesis:– Association between BMI and chronic disease: HTN and cardiovascular,

SGA/IUGR

• Other examples: early diet associations with allergy, obesity, diabetes

Allergies: Prevention by Avoidance (Zeigler, Pediatr Allergy Immunol.

1994)

• High risk infants from atopic families, intervention group n=103, control n=185

• Restricted diet in pregnancy, lactation, Nutramagen when weaned, delayed solids for 6 months, avoided highly allergenic foods

• Results: reduced age of onset of allergies

Allergies: Prevention by

Avoidance (Zeigler, Pediatr Allergy Immunol. 1994)

Definite or Probable Food Allergy

Age Intervention Control p

12 mo 5% 16% 0.007

24 mo 7% 20% 0.005

48 mo 4% 6% ns

Allergies: Early Introduction of Foods

(Fergussson et al, Pediatrics, 1990)

• 10 year prospective study of 1265 children in NZ• Outcome = chronic eczema• Controlled for: family hx, HM, SES, ethnicity,

birth order• Rate of eczema with exposure to early solids

was 10% Vs 5% without exposure• Early exposure to antigens may lead to

inappropriate antibody formation in susceptible children.

Early Introduction of Foods(Fergussson et al, Pediatrics, 1990)

Proportional Hazard Coefficient (p<0.01)For Risk of Chronic Eczema

No solid Food before4 months

1.00

1-3 types of foodbefore 4 months

1.69

4+ types of foodsbefore 4 months

2.87

Allergies: Prevention by Avoidance (Marini, 1996)

• 359 infants with high atopic risk

• 279 in intervention group

• Intervention: breastfeeding strongly encouraged, no cow’s milk before one year, no solids before 5/6 months, highly allergenic foods avoided in infant and lactating mother

Allergies: Prevention by Avoidance (Marini, 1996)

0

20

40

60

80

1 yr 2 yrs 3 yrs

% of Children With Any Allergic Manifestations (cummulative incidence)

non-intervention

intervention

Cochrane Review

• Osborn et al: Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants 2006;18

• Concluded that use of hydrolysed formula in non breastfed infants at risk for allergy (atopic dermatitis) for at least 4 months reduces the incidence of allergy.

DRI

• Nutrition Recommendations from the Institute of Medicine (IOM) of the U.S> National Academy of Sciences for general public and health professionals.

• Hx: WWII, to investigate issues that might “affect national defense”

• Population/institutional guidelines• Application to individuals.

DRI

• Estimated Average Requirement (EAR): expected to satisfy the needs of 50% of the people in that age group based on review of scientific literature.

• Recommended Dietary Allowance (RDA): Daily dietary intake level considered sufficient by the FNB to meet the requirement of nearly all (97-98%) healthy individuals. Calculated from EAR and is usually 20% higher

• Adequate intake (AI): where no RDA has been established.

• Tolerable upper limit (UL): Caution agains’t excess

DRI’s for infants

• Macronutrients based on average intake of breast milk

• Protein less than earlier RDA• Energy: EER

DRI’s for infants

• Macronutrients based on average intake of breast milk

• Protein less than earlier RDA• AAP Recommendations

– Vitamin D: 200 IU supplement for breastfed infants and infants taking <500 cc infant formula

– Iron: Iron fortified formula (4-12 mg/L), Breastfed Infants supplemented 1mg/kg/d by 4-6 months

Feeding Guidelines and Recommendations

• Public health policy

• Health promotion

• Prevention

Recommendations/guidelines

• DRI: Dietary Reference Intakes– AI– UL– EER

• AAP

• Bright Futures

• Start Healthy feeding guidelines

Comparison of individual intake data to a reference or estimate of nutrient needs

• DRI: Dietary Reference Intakes

– periodically revised recommendations (or guidelines) of the National Academy of Sciences

– quantitative estimates of nutrient intakes for planning and assessing diets for healthy people

• AI: Adequate Intake• UL: Tolerable Upper

Intake Level• EER: Estimated Energy

Requirement

DRI’s for infants

• Macronutrients based on average intake of breast milk

– Protein less than earlier RDA– Factors to consider: fetal endowment,

individual variability, impact of diet on bioavailability and need

The Start Healthy Feeding Guidelines for Infants and Toddlers (JADA, 2004)

Bright Futures

• AAP/HRSA/MCHB

• http://www.brightfutures.org

• “Bright Futures is a practical development approach to providing health supervision for children of all ages from birth through adolescence.”

Examples

• Transition

• Supplements to breastmilk

• Safety

• Allergy prevention

• Dental health

• other

Water

Water

• Water requirement is determined by:– water loss

• evaporation through the skin and respiratory tract (insensible water loss)

• perspiration when the environmental temperature is elevated

• elimination in urine and feces.

– water required for growth– solutes derived from the diet

Water

• Water lost by evaporation in infancy and early childhood accounts for more than 60% of that needed to maintain homeostasis, as compared to 40% to 50% later in life

• NAS recommends 1.5 ml water per kcal in infancy.

Renal

• Limited ability to concentrate urine in first year due to immaturities of nephron and pituitary

• Potential Renal solute load determined by nitrogenous end products of protein metabolism, sodium, potassium, phosphorus, and chloride.

Urine Concentrations

• Most normal adults are able to achieve urine concentrations of 1300 to 1400 mOsm/l

• Healthy newborns may be able to concentrate to 900-1100 mOsm/l, but isotonic urine of 280-310 mOsm/l is the goal

• In most cases this is not a concern, but may become one if infant has fever, high environmental temperatures, or diarrhea

Renal solute load

• Samuel Foman J Pediatrics Jan 1999 134 # 1 (11-14)

• RSL is important consideration in maintaining water balance:

• In acute febrile illness• Feeding energy dense formulas• Altered renal concentrating ability• Limited fluid intake

Water Needs

Age Amount of Water (ml/kg/day)

3 days 80-100

10 days 125-150

3 mo. 140-160

6 mo. 130-155

9 mo. 125-145

1 yr. 120-135

2 yr. 115-125

Water

• Individual needs

• Renal concentrating ability

• Solute in diet

• Health

• environment

• Water vs fluid• Concentrating formula decreases free

water and increases RSL• What is the % water in 20 kcal/oz infant

formula?– 90%– To achieve 100 ml/kg/d needs to consume

at least 110 cc/kg/d

Energy Requirements

• Higher than at any other time per unit of body weight

• Highest in first month and then declines• High variability - SD in first months is

about 15 kcal/kg/d• Breastfed infants many have slighly

lower energy needs• RDA represents average for each half

of first year

Energy Requirements, cont.

• RDA represents additional 5% over actual needs and is likely to be above what most infants need.

• Energy expended for growth declines from approximately 32.8% of intake during the first 4 months to 7.4% of intake from 4 to 12 months

Energy Partition in Infancy (kcal/kg/d)

Newborn 6 months

Losses 5 5 Activity 10 25 Thermic effect of feed

10 10

Growth 40 12 Resting Metabolic rate

50 55

Total 115 107

Energy Intakes by Breastfed and Formula Fed Boys (kcal/kg)

Age in Mos. Breastfed Formula1 115 1202 104 1063 95 955 89 956 86 92

2002 Energy DRI

EER

• 0-3 months (89 x wt -100) + 175

• 4-6 months (89 x wt -100) + 56

• 7-12 months (89 x wt -100) + 22

• 13-35 months (89 x wt -100) + 20

• Equations for older children factor in weight, height and physical activity level (PAL)

Examples of EER by age and weight

Age weight total per kg

0-3 months 2 3 4

253 342 431

126 114 108

4-6 months 6 7 8

490 579 668

81 82 83

7-12 months 9 10 11

723 812 901

80 81 81

13-35 months 12 14

988 1166

82 83

Energy

• Correlate individual intake with growth

2002 Carbohydrate DRI

Protein

• Increases in body protein are estimated to average about 3.5 g/day for the first 4 months, and 3.1 g/day for the next 8 months.

• The body content of protein increases from about 11.0% to 15.0% over the first year

2002 Protein DRI

2002 Fat DRI

Essential Fatty Acids

• The American Academy of Pediatrics and the Food and Drug Administration specify that infant formula should contain at least 300 mg of linoleate per 100 kilocalories or 2.7% of total kilocalories as linoleate.

LCPUFA

DHA and ARA

LCPUFA: Backgroundn-6 n-318:2

Linoleic18:3

Linolenic

18:3 linolenic

20:5EPA

20:4Arachidonic

22:6DHA

LCPUFA: Background• Ability to synthesize 20 C FA from 18 C FA is

limited. • n-3 and n-6 fatty acids compete for enzymes

required for elongation and desaturation• Human milk reflects maternal diet, provides

AA, EPA and DHA• n-3 important for neurodevelopment, high

levels of DHA in neurological tissues• n-6 associated with growth & skin integrity

• DHA represents 10% of total FA in brain grey matter, and 35% in rod and cone membranes of retina

• Synthetic ability to convert linolenic acid to DHA present when diet sufficient in w-3 FA (alpha linolenic)

• Alterations in visual and neurodevelopmental fx associate with insufficient DHA

Formula supplementation with long-chain polyunsaturated fatty acids: are there

developmental benefits? Scott et al. Pediatrics, Nov. 1998.

• RCT, 274 healthy full term infants

• Three groups:– standard formula– standard formula with DHA (from fish oil)– formula with DHA and AA (from egg)

• Comparison group of BF

Outcomes at 12 and 14 months

• No significant differences in Bayley, Mental or Psychomotor Development Index

• Differences in vocabulary comprehension across all categories and between formula groups for vocabulary production.

Conclusion

“We believe that additional research should be undertaken before the introduction of these supplements into standard infant formulas.”

PUFA Status and Neurodevelopment: A summary and critical analysis of the literature (Carlson and Neuringer, Lipids, 1999)

• In animal studies use deficient diets through generations - effects on newborn development may be through mothering abilities.

• Behaviors of n-3 fatty acid deficient monkeys: higher frequency of stereotyped behavior, locomotor activity and behavioral reactivity

Efficacy and safety of docosahexaenoic acid and arachidonic acid addition to infant formulas: can

one buy better vision and intelligence?

(Koo. J Am Coll Nutr. 2003 Apr;22(2):101-7)

• “Functional benefits in particular visual or neural development from IF containing LCPUFA remains controversial.”

• “Potential for excessive and/or imbalanced intake of n-6 and n-3 fatty acids exists with increasing fortification of LCPUFA to infant foods other than IF.”

Formula Supplemented with DHA & ARA: A Critical Review of the Research (Wright et al, 2006)

• 10 RCTs from 1997-2003 of variable quality

• Considered the strength of each study by looking at indices of research quality.

Wright et al, cont.

• Growth (7 studies)– no differences in weight, length, OFC

• FA in blood (7 studies) – DHA & ARA higher with supplementation– those supplemented with only DHA had lower

levels of ARA than those on standard formula– Supplementation with LCPUFA for only 17 weeks

lead to higher EFA levels at 1 year of age

Wright et al, cont.

• Vision (6 trials)– 2 found better visual function with LCPUFA

, 4 did not

• Neurodevelopment – 1 of 4 found positive results on Bayley

Scales of Infant Development II– 2 of 5 found positive information

processing/IQ/cognitive effects

Wright et al, cont

• Conclusions– No detrimental effects found– Possibly a small improvement in visual

acuity, but significance of this small effect in global development is questionable

– “thoughtful consideration is advised before recommending more expensive formula for term infants.”

Longchain polyunsaturated fatty acid supplementation in infants born at term

(Cochrane, 2001).

• At present there is little evidence from randomised trials of LCPUFA supplementation to support the hypothesis that LCPUFA supplementation confers a benefit for visual or general development of term infants.

• A beneficial effect on information processing is possible but larger studies over longer periods are required to conclude that LCPUFA supplementation provides a benefit when compared with standard formula.

• Data from randomised trials do not suggest that LCPUFA supplements influence the growth of term infants

Omega-3 FA and Neural Development to 2 years of Age: Do we Know enough for Dietary Recommendations: Innis JPGN

48:S16-24:2009

• Estimated requirement and variability among individuals necessary to set DRI

• Dietary recommendations affect food supply and supplements and are used in labeling

• When scientific information is incomplete, consideration must be given to implications of recommendations

Omega-3 FA and Neural Development to 2 years of Age: Do we Know enough for Dietary Recommendations: Innis JPGN

48:S16-24:2009

• “ While there is no doubt that DHA is critical for the developing brain, western diets poor in w-3 FA and rich in w-6 FA are becoming increasingly implicated in contributing to risk of poor neurodevelopment and function…..The w-3 FAs are clearly essential nutrients, suggesting that dietary recommendations, such as AI, to minimize risk of poor CNS development can be justified, and are consistent with a philosophy of dietary advice that promotes optimal child development and health. However, because dietary recommendations often promulgate changes in the food supply and supplement use…..premature recommendations based on incomplete science that focus on individual nutrients rather than dietary practices such as breastfeeding and foods such as fish rich in DHA are not necessarily in the best public interest”

Vitamin K

Vitamin K

• 2 forms: K1 or phylloquinone (plant form) and K2 (synthesized by bacteria)

• Function: cofactor inmetabolic 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

• 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

Vitamin K Controversy

• Adequacy of BM

• Maternal Diet and Vitamin A content of BM

• ? Significance/prevalence of hemorrhagic disease of newborn

• IM injections of all newborns

Controversies Concerning Vitamin K and the

Newborn: AAP Policy Statement, 2003

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

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

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.

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.

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

• Note put recent articles on re-emergence of HDNB texas, ? Japan

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 g (400 IU) per day for breastfeed infants

• 2003: American Academy of Pediatrics recommends supplements of 5 g (200 IU) per day for all infants as recommended in DRIs.

• 10/14/2008: AAP updates guidelines vor 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, 2003

• 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

Iron

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 an 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

• 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 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 2.1

Above poverty 8.9 2.2

Below poverty 8.6 2.3

Enrolled 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

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.

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:2010

Pediatrics 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)

AAP recommendations for Dx and prevention of ID and IDA:2010

Pediatrics 2010 126 #5

• 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.

AAP recommendations for Dx and prevention of ID and IDA:2010

Pediatrics 2010 126 #5

• 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

AAP recommendations for Dx and prevention of ID and IDA:2010

Pediatrics 2010 126 #5

• 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

AAP recommendations for Dx and prevention of ID and IDA:2010

Pediatrics 2010 126 #5

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

content. Liquid supplement may be needed to augment complimentary foods

AAP recommendations for Dx and prevention of ID and IDA:2010

Pediatrics 2010 126 #5

• 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

Lead and Anemia

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.

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

Infant Feeding

• Implications• Translation into practice• Recommendations