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Looking Beyond the Basics of Infant Nutrition
Learning Objectives
By the end of this session, physicians will be able to:
– Identify the importance of counselling on infant nutrition
– Recognize that optimizing infant nutrition requires considerations beyond the basics
Such that they will:
– Consistently, proactively and confidently counsel on optimal infant nutrition
Why do we need to counselon infant nutrition?
Why wouldn’t we counselon infant nutrition?
Why We Should Counsel onInfant Nutrition
Growth and development are rapid in early life1,2
Certain nutritional components are associated with development and health3‐6
Early nutrition counseling may:
– Help optimize development
– Provide the foundation for lifelong nutrition
1. Jung E, et al. Am J Clin Nutr 1985;42(2):182‐9.2. Bowden VR, et al. Children and their families: the continuum of care. Philadelphia: Lippincott Williams & Wilkins, 2010.3. Morale SE, et al. Early Hum Dev 2005;81:197‐203.4. Birch EE, et al. Am J Clin Nutr 2010;91(4):848‐59.5. Ward LM, et al. CMAJ 2007;177(2):161‐6.6. American Academy of Pediatrics Committee on Nutrition. Pediatrics 1999; 104(1):119‐23.
The Basics
Macronutrients in breast milk
Macronutrients in Breast Milk,The Gold Standard of Infant Nutrition
Adapted from Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL: AAP; 2009.
Macronutrient Composition of Breast Milk
Nutrient% of
calories1Important Characteristics
Protein 6%Protein composition: Intact
Whey:casein ratio: 60:402*
Carbohydrate 43%Primary source: Lactose1
>200 oligo‐ and polysaccharides3
Lipids 51%Polyunsaturated fatty acids:DHA [omega‐3] = 0.32% of total fatty acids4†
ARA [omega‐6] = 0.47% of total fatty acids4†
*Whey:casein ratio of typical mature breast milk (15 days to 6 months after birth); †Average level of DHA and ARA in breast milk (mean ± standard deviation of total fatty acids) based on an analysis of 65 studies of 2,474 women.
Adapted from:1.Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL: AAP; 2009.2.Kunz C, et al: Acta Paediatr 1992; 81:107‐12.3.Niñonuevo MR, et al: J Agric Food Chem 2006; 54:7471‐80.4.Brenna JT, et al: Am J Clin Nutr 2007; 85:1457‐64.
Growth Charts for Length, Weight & Head Circumference: 0 – 24 Months
Downloaded from www.dietitians.ca/growthcharts, April 2012.
Beyond the Basics
Infant Nutrition is More ThanJust Calories!
Health(Modulates host protective
mechanisms)
Health(Modulates host protective
mechanisms)
Development and CognitionDevelopment and Cognition
The Importance of Infant Nutrition
Expert opinion: Drs. David Mack and Valerie Marchand, 2012.
Body growthBody growth
The basics
The basics
Specific Organ HealthSpecific Organ Health
Beyond the basics
Beyond the basics
Dietary
Intake
Dietary
Intake
Mother's milk:A Potential Goldmine of Components
harmacol Ther 1994;62(1‐2):193‐220.dscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
Breast milk
Breast milk
FatsFats
CarbohydratesCarbohydrates
Human milkimmunoglobulins
Human milkimmunoglobulins
Fat‐soluble vitaminsFat‐soluble vitamins
Other immunologiccomponents
Other immunologiccomponents
MineralsMinerals
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Components of Breast Milk To Be Reviewed
Adapted from: Bates CJ, et al. Pharmacol Ther 1994;62(1‐2):193‐220.Wagner CL: Medscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
FatsFats
CarbohydratesCarbohydrates
Human milkimmunoglobulins
Human milkimmunoglobulins
Fat‐soluble vitaminsFat‐soluble vitamins
Other immunologiccomponents
Other immunologiccomponents
MineralsMinerals
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Breast milk
DHA &ARA
DHA &ARA
PrebioticsPrebiotics
Vitamin DVitamin D
IronIron
Health(Modulates host
protective mechanisms)
Health(Modulates host
protective mechanisms)
Development and Cognition
Development and Cognition
Specific Organ HealthSpecific Organ Health
Components of Breast Milk Studied: Fats
Expert opinion: Drs. David Mack and Valerie Marchand, 2012.Adapted from: Bates CJ, et al. Pharmacol Ther 1994;62(1‐2):193‐220.
Wagner CL: Medscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
FatsFats
CarbohydratesCarbohydrates
Human milkimmunoglobulins
Human milkimmunoglobulins
Fat‐soluble vitaminsFat‐soluble vitamins
Other immunologiccomponents
Other immunologiccomponents
MineralsMinerals
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Dietary IntakeDietary Intake
DHA &ARA
DHA &ARA
Omega‐3, ‐6 and ‐9 Fatty Acids
Omega‐6
Linoleic acid
↓
γ‐linolenic acid
↓
Dihomo‐γ‐linolenic acid
↓
Arachidonic acid (ARA)
Omega‐6
Linoleic acid
↓
γ‐linolenic acid
↓
Dihomo‐γ‐linolenic acid
↓
Arachidonic acid (ARA)
Omega‐3
α‐linolenic acid (ALA)
↓
Octadecatetraenoic acid
↓
Eicosatetraenoic acid
↓
Eicosapentaenoic acid (EPA)
↓
Docosapentaenoic acid
↓
Docosahexaenoic acid (DHA)
Omega‐3
α‐linolenic acid (ALA)
↓
Octadecatetraenoic acid
↓
Eicosatetraenoic acid
↓
Eicosapentaenoic acid (EPA)
↓
Docosapentaenoic acid
↓
Docosahexaenoic acid (DHA)
Omega‐9
Oleic acid
↓
Octadecadienoic acid
↓
Eicosadienoic acid
↓
Eicosatrienoic acid
Omega‐9
Oleic acid
↓
Octadecadienoic acid
↓
Eicosadienoic acid
↓
Eicosatrienoic acid
Adapted from:1. Tvrzicka E, et al. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155(2):117‐30.2.Das UN. Curr Pharm Biotechnol 2006;7(6):467‐82.3.Wallis JG, et al. Trends Biochem Sci 2002;27:467‐73.4.Russo GL. Biochem Pharmacol 2009;77(6):937‐46.
• Fatty acids not synthesized by humans:1
– Linoleic (omega‐6): fatty acid with 18 carbons and 2 double bonds – 18:2 (9,12)
– Linolenic (omega‐3): fatty acid with 18 carbons and 3 double bonds – 18:3 (9,12,15)
• Requirements: 2‐3% of daily calories2
Essential Fatty Acids: Omega‐3 and Omega‐6
Adapted from:1. Das UN: Curr Pharm Biotechnol 2006;7(6):467‐82.2. Expert opinion: Drs. David Mack and Valerie Marchand, 2012.
HH
H H HHH
H HH
HH
HH
HHH
H HH
HH
HH
CC
C C CCC
C CC
CC
CCH
H H H
C C C
HO
OH
C
Metabolism of DHA and ARA: Important Building Blocks of the Developing Brain and Immune System
Arachidonicacid (ARA)
Eicosanoids(mainly pro‐inflammatory)
Omega‐6:Linoleic acid (LA)
Membranes throughout the body,including brain and immune cells
Adapted from Serhan CN, Savill J. Nature Immunol 2005;12:1191‐7.
Immune Cells
Eicosapentaenoicacid (EPA)
Eicosanoids(anti‐inflammatory)
Omega‐3:‐linolenicacid (ALA)
Physiologic Mediators
Docosahexaenoicacid (DHA)
Membranes(especially in retina and other
brain cells)
Docosanoids(anti‐inflammatory)
LCPUFAs
Preformed DHA Allows for more Predictable Bioavailability Compared to Converted DHA
Intake of biochemicalprecursor:
Alpha‐linolenic acid(short‐chain omega‐3 fat)
1. Innis SM. Early Hum Dev 2007;83(12):761‐6.
>>
in utero in breastmilk
insupplementedinfant formula
DHA
Endogenous synthesisConversion rate is very low (< 1% of alpha‐linolenic acid
is converted to DHA)1
DHA
Preformed DHA…
Prenatal Nutrition is Critical: Important Neurologic Developments In Utero
Domain Developments
Cognitive100 billion neurons form
Eyes develop and make movements
Motor
Arms and legs move
Thumb sucking
Development of touch
LanguageMouth opens and closes
Response to sounds
Social skills Response and habituation to familiar sounds
Adapted from Herschkowitz N, et al: A Good Start in Life: Understanding Your Child’s Brain and Behavior from Birth to Age 6. 2004.
Adapted from Dobbing J, et al. J Arch Dis Child 1973; 48:757‐67.
Brain Growth is Rapid in the Last Trimester and First 2 Years of Life
‐6 0 6 12 18 24 30 36
400
800
1200
1600
Age (months)
Brain W
eight (grams) Term
~+260%
~+175%
~+18%
Adult~+21%
Adapted from Martinez M. J Pediatr 1992;120(suppl):S129‐38.
Differential Accumulation ofOmega‐3 Fats in the Brain: DHA is the Key
0
2000
4000
6000
8000
10000
12000
‐20 0 20 40 60 80 100 120
Postnatal Age (weeks)
w‐3 LCPUFA
(mcm
olin forebrain)
DPA
DHA
EPA
Placenta Diet and
Synthesis
DHADPA
EPA
DHA is an Important Building Blockof the Growing Brain
Adapted from Martinez M. J Pediatr 1992;120(suppl):S129‐38.
Changes in the Brain Help to Foster Development in Early Life
Adapted from:1. Eliot L. What’s Going on in There? How the Brain and Mind Develop in the First Five Years of Life; 1999.2. McDevitt TM, et al. Child Development: Educating and Working With Children and Adolescents. 2nd ed.; 2003.3. Restak R. The Secret Life of the Brain; 2001.4. Shonkoff JP, ed. Handbook of Early Childhood Intervention. 2nd ed.; 2000.5. Drover JR, et al. Child Dev 2009;80:1376‐84.
The motor cortex develops and connects to nerve pathways throughout the body, facilitating advancing motor control.1
The motor cortex develops and connects to nerve pathways throughout the body, facilitating advancing motor control.1
With more neural connections and faster processing in the occipital lobe, vision becomes more refined over time.1,2
With more neural connections and faster processing in the occipital lobe, vision becomes more refined over time.1,2
Neurons plug into different areas of the brain contributing to language development.3
Neurons plug into different areas of the brain contributing to language development.3
As neurons build stronger connections in the prefrontal cortex, higher level thinking emerges, including attention, forethought, planning, and problem solving.1,4,5
As neurons build stronger connections in the prefrontal cortex, higher level thinking emerges, including attention, forethought, planning, and problem solving.1,4,5
The developing frontal cortex coordinates emotional connections. As it matures, children begin to feel and show affection.1
The developing frontal cortex coordinates emotional connections. As it matures, children begin to feel and show affection.1
Neurocognitive Benefits of Recommended Levels of DHA in Infant Formula vs. Formula with no DHA
*Studies compared infants formula containing DHA and ARA (0.32% and 0.64%) and formula without DHA and ARA.Adapted from:1.Koletzko B, et al. J Perinat Med 2008;36:5‐14.2.Colombo J, et al. Ped Res 2011;70:406‐103.Drover JR, et al. Child Dev 2009;80:1376‐84.4.Morale SE, et al. Early Hum Develop 2005;81:197‐203.5.Birch EE, et al. Dev Med Child Neurol 2000;42:174‐81.
Expert‐recommended level of DHA1*
Expert‐recommended level of DHA1*
Improved visual acuity at 12 months4*Improved visual acuity at 12 months4*
38% longer sustained attention at 9 months2*38% longer sustained attention at 9 months2*
Improved problem solving:63% more successesat 9 months3*
Improved problem solving:63% more successesat 9 months3*
Improvement in Mental Development Index scores at 18 months5*Improvement in Mental Development Index scores at 18 months5*
DHA Intakes of Pregnant Canadian Women Are Very Low
*Trace amount (<2 mg/d)†Recommended intake for pregnant women (Koletzko B, et al. J Perinat Med 2008;36:5‐14.)
Adapted from Denomme J, et al. J Nutr 2005;135(2):206‐11.
Study Participants (n=20)
DHA Intake (mg/day)
*
†
700
100
200
300
400
600
500
* * *
Individualresults
Group meanresult
Recommended Dietary DHA and ARA Intake for Pregnant and Lactating Women
Adapted from Koletzko B, et al. J Perinat Med 2008;36:5‐14.
• ≥ 200 mg of dietary / supplemental DHA
• ARA intake should be equivalent to DHA
Expert Positions for DHA and ARA Levels in Term Infant Formulas
DHA ARA
World Assoc. of Perinatal Med./Early Nutrition Academy/Child Health Foundation (2008)1
0.2‐0.5 ≥0.2
American Dietetic Association (ADA) and Dietitians of Canada (DC) position (2007)2
≥0.2 ≥0.2
Child Health Foundation, Germany (2001)3 ≥0.2 ≥0.35
Expert panel convened by ISSFAL (1999)4 ~0.35 ~0.5
British Nutrition Foundation (1992)6 ~0.4 ~0.4
Adapted from:1. Koletzko B, et al. J Perinat Med 2008;36:5‐14.2. Kris‐Etherton PM, et al. J Am Diet Assoc 2007;107:1599‐1611.3. Koletzko B, et al. Acta Paediatr 2001;90:460‐4.4. Simopoulos AP, et al. J Am Coll Nutr 1999;18:487‐9.5. FAO/WHO Joint Expert Consultation. Lipids in Early Development. FAO Food and Nutr Pap 1994;57:49‐55.6. The British Nutrition Foundation. Unsaturated Fatty Acids: Nutritional and Physiological Significance. London, England: Chapman & Hall; 1992:152‐163.
DHA & ARA: Implications for Counselling
DHA & ARA are important building blocks for brain and eye development1‐4
For pregnant women and nursing mothers: Diet should include DHA‐rich foods / supplements5
For formula‐fed infants:
─ Formulas containing DHA and ARA should be preferred over non‐supplemented formulas6
─ Ensure that the formula has DHA and ARA levels within the range demonstrated to have an impact on outcomes6
1. Colombo J, et al. Ped Res 2011;70:406‐10.2. Drover JR, et al. Child Dev 2009;80:1376‐84.3. Morale SE, et al. Early Hum Dev 2005;81:197‐203.4. Birch EE, et al. Dev Med Child Neurol 2000;42:174‐81.5. Koletzko B, et al. J Perinat Med 2008;36:5‐14.6. Expert opinion: Drs. David Mack and Valerie Marchand, 2012.
Health(Modulates host
protective mechanisms)
Health(Modulates host
protective mechanisms)
Development and Cognition
Development and Cognition
Specific Organ HealthSpecific Organ Health
Components of Breast Milk Studied:Fat‐soluble Vitamins
Fat‐soluble vitaminsFat‐soluble vitamins
FatsFats
CarbohydratesCarbohydrates
Human milkimmunoglobulins
Human milkimmunoglobulins
Other immunologiccomponents
Other immunologiccomponents
MineralsMinerals
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Dietary IntakeDietary Intake
VitaminD
VitaminD
Expert opinion: Drs. David Mack and Valerie Marchand, 2012.Adapted from: Bates CJ, et al. Pharmacol Ther 1994;62(1‐2):193‐220.
Wagner CL: Medscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
Vitamin D‐Deficiency Rickets in Canadian Children
Incidence: 2.9 per 100,000 – 104 confirmed cases (2002‐2004)
– Mean age at diagnosis: 1.4 years
Risk factors for children:– Of the 94% of children that were breastfed
89% of these did not receive Vitamin D supplementation
– 89% were of intermediate or dark skin
Maternal contributing factors:– Limited sun exposure
– Lack of vitamin D (diet, supplements) during pregnancy or lactation
Adapted from Ward LM, et al. CMAJ 2007; 177(2):161‐6. © 2011 Mead Johnson Nutrition [Canada] Co.
Vitamin D in Breast Milk
Breast milk contains almost all the nutrients a growing infant requires, but can be low in vitamin D
Hollis BW, et al: J Nutr 1981; 111(7):1240‐8.
Vitamin D:Implications for Counselling
For nursing mothers: – Supplement diet to achieve intake of at least
600 IU daily1
For breastfed infants:– Daily supplement of 400 IU1
– Infants who receive limited amounts of formula as supplemental feeds likely still require vitamin D supplementation to meet daily requirements
For formula fed infants:– Formulas provide adequate vitamin D – no
further supplementation is required21. Health Canada.Vitamin D and Calcium: Updated Dietary Reference Intakes. Accessed on‐line April, 2012. www.hc‐sc.gc.ca2. Canadian Paediatric Society. Paediatric Child Health 2007;12:583‐9.
Health(Modulates host
protective mechanisms)
Health(Modulates host
protective mechanisms)
Development and Cognition
Development and Cognition
Specific Organ HealthSpecific Organ Health
Components of Breast Milk Studied: Minerals
MineralsMinerals
Fat‐soluble vitaminsFat‐soluble vitamins
FatsFats
CarbohydratesCarbohydrates
Human milkimmunoglobulins
Human milkimmunoglobulins
Other immunologiccomponents
Other immunologiccomponents
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Dietary IntakeDietary Intake
IronIron
Expert opinion: Drs. David Mack and Valerie Marchand, 2012.Adapted from: Bates CJ, et al. Pharmacol Ther 1994;62(1‐2):193‐220.
Wagner CL: Medscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
Effects of Iron Deficiency on Growth and Development
Short‐term1‐4
Poor weight gain1
Weakness and muscle fatigue2
Abnormal GI motility2
Irritability and shorter attention span3,4
Exercise intolerance and lower physical activity3
Longer‐term5‐7
Motor development sensitive to mild‐iron deficiency anemia
Reduction in cognitive ability and mental skills in severe and chronic iron deficiency
Poor school performance in middle school associated with early childhood anemia
Evidence does not specify specific cognitive deficitsAdapted from:
1. Aukett MA, et al. Arch Dis Child 1986;61(9):849‐57.2. American Academy of Pediatrics Committee on Nutrition: Pediatrics 1999;104(1):119‐23.3. Wu AC, et al. Screening for iron deficiency. Pediatr Rev 2002;23(5):171‐8.4. Lozoff B. Bull N Y Acad Med 1989;65(10):1050‐66.5. Booth IW, et al. Arch Dis Child 1997;76:549‐53.6. Beard JL, et al. Nutr Rev 1993;51:157‐70.7. Grantham‐McGregor S, et al. J Nutr 2001;131:S649‐68.
Signs/Symptoms of Iron Deficiency Anemia
Clinical signs are helpful only in severe cases
In mild iron deficiency, laboratory tests may be less reliable; values overlap with iron‐sufficient individuals
Oski F. N Engl J Med 1993;329(3):190‐3.
Signs / Symptoms of moderately severe iron deficiency
↓mean cell volume
↓ serum ferritin level
↓ serum iron level
↑ serum iron‐binding capacity
↑ red‐cell protoporphyrin level
↑ red‐cell distribution width
↑ hemoglobin concentration after institution of iron therapy
Iron: Implications forCounselling—Breastfeeding
Full‐term breastfed infants do not require iron supplementation1
– Breast milk is relatively low in iron, but it is bioavailable (20‐50%)1
– Level of iron in breast milk declines over time1
Introduce solid foods as recommended at6 months (starting with iron‐fortified cereal)2
1. Griffin IJ, et al. Pediatr Clin North Am 2001; 48(2):401‐13.2. Health Canada. Nutrition for Healthy Term Infants ‐ Statement of the Joint Working Group: Canadian Paediatric Society, Dietitians of Canada and Health
Canada. Ottawa 2005.
Iron: Implications forCounselling—Formula Feeding
Infant formulas are iron fortified and so contain adequate concentrations of exogenous iron1
– Higher levels required due to relatively low bioavailability (3‐10%)1
– No additional iron supplementation is required in full term infants2
– There is no indication for non‐iron‐fortified infant formula
Introduce solid foods as recommended at 6 months (starting with iron‐fortified cereal)3
Cow milk not recommended until 12 months of age2
Adapted from:1. Faldella G, et al: Acta Paediatr Suppl 2003; 91(441):82‐5.2. Baker RD, et al: Pediatrics 2010; 126(5):1040‐50.3. Health Canada. Nutrition for Healthy Term Infants ‐ Statement of the Joint Working Group: Canadian Paediatric Society, Dietitians of Canada and Health
Canada. Ottawa 2005.
Components of Breast Milk Studied: Carbohydrates
Expert opinion: Drs. David Mack and Valerie Marchand, 2012.Adapted from: Bates CJ, et al. Pharmacol Ther 1994;62(1‐2):193‐220.
Wagner CL: Medscape Reference: Drugs, Diseases and Procedures. Updated December 4, 2010.
Health(Modulates host
protective mechanisms)
Health(Modulates host
protective mechanisms)
Development and Cognition
Development and Cognition
Specific Organ HealthSpecific Organ Health
CarbohydratesCarbohydrates
Fat‐soluble vitaminsFat‐soluble vitamins
FatsFats
Human milkimmunoglobulins
Human milkimmunoglobulins
Other immunologiccomponents
Other immunologiccomponents
MineralsMinerals
Water‐soluble vitaminsWater‐soluble vitamins
EnzymesEnzymes
Growth modulatorsGrowth modulators
ProteinsProteins
Dietary IntakeDietary Intake
PrebioticsPrebiotics
Microbiota Development in Infants
Microbiota is essential for GI and immune development
Colonization begins during early life, affected by delivery method, feeding & gestational age1
– Diversity of microbiota affects immune maturation2
1. Penders J, et al. Pediatrics 2006;118(2):511‐21.2. Adlerberth I, et al. Acta Paediatr 2009;98(2):229‐38.
Human milk oligosaccharides (HMOs) are food for friendly bacteria like Bifidobacterium infantis. Shorter chain HMOs in particular are almost entirely consumed by this microbe.
Milk Macro‐/Micronutrients HMOs
1010
88
77
66
99
88
55
44
Other HMOsof longerlengths
Proportioneaten byB. infantis
Chainlength
Prebiotics in Breast Milk:Human Milk Oligosaccharides
Adapted from Petherik A, et al. Nature 2010;468:S5‐S7.
Human Milk Oligosaccharides (HMOs)
Large component of breast milk (5‐10 g/L)
Complex mixture of galacto‐oligosaccharides
Bifidogenic properties
Concentration affects microbiomecomposition
Normally, not present in infant formulas
– Rationale for adding prebiotics to formula:
functional substitution for HMOs
1. Zivkovic AM, et al. Proc Natl Acad Sci U S A 2011;108 Suppl 1:4653‐8.2. Coppa GV, et al. J Pediatr Gastroenterol Nutr 2011;53(1):80‐7.
Beneficial Bacteria Play a Key Role in Inhibiting Pathogens in the GI Tract
Adapted from:Knol J, et al. J Pediatr Gastroenterol Nutr 2005;40(1):36‐42. Niers L, et al: Nutr Rev 2007;65(8 Pt 1):347‐60.
Microbiota Development:Prebiotics vs. Probiotics
Prebiotics Probiotics
Definition Nondigestible food ingredients that selectively stimulate the growth and/or activity of a limited number of bacteria in the colon that are thought beneficial to host health1
Live microorganisms which, when administered in adequate amounts, confer a health benefit
Purpose in Infant Nutrition
Functional substitution for human milk oligosaccharides
Specific probioticsare useful for specific conditions, including cow milk protein allergy and diarrhea
Adapted from Roberfroid M. J Nutr 2007;137(3 Suppl 2):830S‐7S.
Actions of Prebiotics
Expert opinion Dr. David Mack,Adapted from Sherman P, et al. J Pediatr 2009;155:S61‐70.
Prebiotice.g., fructooligosaccharides, galactooligosaccharides, polydextrose, lactulose
Prebiotice.g., fructooligosaccharides, galactooligosaccharides, polydextrose, lactulose
Colonic microbia↑ Bifidobacteria↑ Lactobacillii
Colonic microbia↑ Bifidobacteria↑ Lactobacillii
Energy source forcolonocytes
Energy source forcolonocytes
Enhanced absorption of calciumEnhanced absorption of calcium
Reduced pHReduced pH
Short‐chainfatty acids
Short‐chainfatty acids
Lacticacid
Lacticacid
Antimicrobialeffect
Antimicrobialeffect
Healthmaintenance
Healthmaintenance
Health benefit(e.g., softer, more
bulky stools
Health benefit(e.g., softer, more
bulky stools
Not digested or absorbed instomach or small intestine
Fermentation of carbohydrates
Prebiotic Supplementation of Formula forFull‐term Infants: Systematic Review of 11 RCTs
Stools softer (5 of 5 trials)
Stools more frequent (3 of 3 trials) and similar to number of breastfed infants
Stool pH lowered (7 of 8 trials)
– Weighted average ‐0.65 (95% CI ‐0.76 to ‐0.54)
Stool Bifidobacteria increased (6 of 9 trials)
Prebiotics studied:
– GOS, FOS, long chain FOS, PDX, lactulose
– Combinations or singly, total prebiotic: 0.3 g/dL‐0.8 g/dL
n=1,459Rao S, et al. Arch Pediatr Adolesc Med 2009;163(8):755‐64.
Prebiotic Blend of GOS/PDX in Full‐Term Healthy Infants: Study Summary
Methodology: 60‐day intervention study230 healthy, full‐term infants, aged 21‐30 days
Randomized to formula with GOS/PDX prebiotics or control formula with no prebiotics (also, a breast milk control arm)
Results: Primary: No significant differences between formulas in Bifidobacteria counts at 60 days (FISH analysis)
Secondary: GOS/PDX formula was associated with:
– Higher Bifidobacteria counts than control at 60 daysand similar to breast milk fed (qPCR analysis)
– Softer stools at all time points
Scalabrin DM, et al. J Pediatr Gastroenterol Nutr 2012;54(3):343‐52.
Current Expert Consensus Opinions on Prebiotic‐Supplemented Infant Formulas
More data are required for recommendation of prebiotics in formula (AAP and ESPGHAN)1,2
No safety concerns (growth or adverse effects) with prebiotic supplementation (ESPGHAN)2
1. Thomas DW, et al. Pediatrics 2010;126(6):1217‐31.2. Braegger C, et al. J Pediatr Gastroenterol Nutr 2011;52(2):238‐50.
Prebiotics: Implications for Counselling
For nursing mothers:– Diversity
o Breast milk oligosaccharides
o Infant microbiota
o Importance?
For formula‐fed infants:– Evidence shows softer stool consistency
– Work underway regarding other outcomes
Other Important Aspects of Nutrition Counselling
Other Mammalian Milks Do Not Have the Proper Balance for Infant Nutrition
Appropriate
Breast milk
Infant formula
Not Appropriate
X Cow's milk
X Other mammalian milks (e.g., goat)
X Plant‐based beverages (e.g., soy, rice, almond, hemp)
Health Canada. Nutrition for Healthy Term Infants ‐ Statement of the Joint Working Group: Canadian Paediatric Society, Dietitians of Canada and Health Canada. Ottawa 2005.
What if we had an acronym/ reminder to help us counsel parents?
What could it be?
Helping Parents be Proactive in Infant Nutrition: COUNSEL: A Mnemonic Counselling Tool
C Confirm that breastfeeding is the preferred primary source of infant nutrition.
O Optimize the mother's nutritional intake: recommend a balanced, healthy diet.
U Underline the importance of certain components of the maternal diet (DHA and vitamin D).
N Never use other milks (e.g., cow, goat, plant‐based) as the primary infant food.
S Supplement the breastfeeding infant’s diet with vitamin D, 400 IU daily.
E Educate all parents about formula feeding: choose formula with adequate DHA & ARA levels, consider formula with prebiotics.
L Labels: Encourage parents to read formula labels to ensure levels of DHA & ARA proven to have an effect on health & development.
Beyond the Basics of Infant Nutrition
Summary
Key Learning Points from This Session (1)
Healthcare professionals need to counsel parents on infant nutrition. Why Wouldn't We?
Breastfeeding mothers need:
To eat a healthy diet.
Adequate DHA from diet / supplements.
To supplement the infant's diet with vitamin D.
Key Learning Points from This Session (2)
When transitioning off breast milk (or choosing not to breastfeed):
Iron‐fortified formula is the food of choice.
Choose formula with appropriate levels of DHA & ARA.
Consider choosing formula with prebiotics.
The Future of Infant Nutrition
We Are What We Eat…Future Understanding
Nutrients can modify physiologic and pathologic processes through epigenetic mechanisms and thus potentially play a role in disease prevention and maintenance of health.
‐ Choi SW, et al. Adv Nutr 2010
(Epigenetics refers to the heritable changes in gene expression that change the underlying DNA sequence. Examples are DNA methylation and histone modification.)
We Are What We Eat…Future Understanding
The human component of the total DNA in our bodies is 0.3%1
The other 99.7% is of microbial origin1
The intestinal microbiota may be influenced by dietary intake2,3
The human gut microbiome (the collective community of microbes and their total genome capacity) have been implicated in health and disease4
Adapted from:1. Qin J, et al. Nature 2010;464(7285):59‐65.2. Hehemann JH, et al. Nature 2010;464(7290):908‐12. 3. Davis LM, et al: PLoS One 2011;6:e25200.4. Young VB. Curr Opin Gastroenterol 2012;28:63‐9.
Remember C.O.U.N.S.E.L.
COUNSEL helps participants achieve one of this program's key learning objectives:
To be able to consistently, proactively and confidently counsel on optimal infant nutrition.
Supplemental Slides
Improvement in Attention with DHA‐Supplemented Formula
Adapted from Colombo J, et al. Pediatr Res 2011;70(4):406‐10.
38% longerattentionp<0.05
0.5
0.1
0.2
0.3
0.4
00% DHA 0.32% DHA
0.412
0.298
Proportion of time spen
t in
sustained
atten
tion (9 m
onths)
Means‐End Problem Solving Improved in Babies Fed DHA/ARA Supplemented Infant Formula12‐Month Feeding, 6‐Week Weaning, or 4‐ to 6‐Month Weaning
Adapted from Drover JR, et al. Child Dev 2009;80:1376‐84.
Control Formula with DHA (DHA 0.36% & ARA 0.72%)
Average intention score
*
*
10
9
8
6
5
7
4
2
1
012‐monthfeeding
6‐weekweaning
4‐ to 6‐monthweaning
3
Intentional solutions (median)
*p<0.05
†*
*
3
2.5
3.5
2
1
0.5
012‐monthfeeding
6‐weekweaning
4‐ to 6‐monthweaning
1.5
Longer Feeding with Dietary DHA (Breast Milk or DHA/ARA Supplemented Formula) Improves Visual Acuity
Adapted from Morale SE, et al. Early Hum Dev 2005;81:197‐203.
Dietary DHA for 52 weeks
No dietary DHA for 52 weeks
~1.5‐line difference
Sweep VEP
Acuity
(SnellenValues)
20/50
20/40
20/30
20/25
Duration of Dietary DHA Supply (weeks)
~20/41
~20/32 ~20/28~20/36
0weeks
17weeks
35weeks
52weeks
Breast milk
Formula with DHA (0.32%)
Breast milk + formula with DHA (0.32%)
Formulawith Iron
DHA Levels and Mental Development:Bayley MDI Scores
Adapted from:1.Birch EE, et al. Dev Med Child Neurol 2000;42:174‐81.2.Hoffman DR, et al. FASEB J 2003;17:A727‐A728. Abstract 445.1.3.Auestad N, et al. Pediatrics 2001;108:372‐81.
Birch/Hoffman StudyMDI at 18 months
Score
*P < 0.05 vs.Control
**
105
0
95
100
Formula with DHA (0.36%) + ARA (0.72%)
Control formula
Breast milk (DHA 0.29% + ARA 0.56%)
Auestad StudyMDI at 12 months
Norm
105
0
95
100
Formula with DHA (0.13%) + ARA (0.46%)
Control formula
Breast milk (DHA 0.12% + ARA 0.51%)
Visual Acuity Corresponds withDHA Levels in Formula‐fed Infants
p<0.002 or less at all agesn=294 at 1.5 months; n=268 at 4 months; n=253 at 9 months; n=241 at 12 months.
Adapted from Birch EE, et al. Am J Clin Nutr 2010;91:848‐59.
Sweep VEP Acuity (logM
AR)
Age (months)
0.40
0.60
0.80
1.00
0 1 2 3 4 5 6 7 8 9 10 11 120.00
0.20
Snellen
20/50
20/25
20/200
20/100
0.96
0.00
0.32
0.64
DHA level
DHA and ARA Levels in Breast MilkAre Variable
Adapted from:1. Brenna JT, et al. Am J Clin Nutr 2007;85:1457‐64.2. Auestad N, et al. Pediatrics 2001;108:372‐81.3. Birch EE, et al. Pediatr Res 1998;44:201‐9. 4. Innis SM. J Pediatr 2003;143(4 Suppl):S1‐8.
LocationDHA
(% fatty acids)ARA
(% fatty acids)
Japan 0.99 0.40
Philippines 0.74 0.39
Chile 0.43 0.42
China 0.35 0.49
Worldwide Mean (Brenna) 0.32 0.47
United States (Birch) 0.29 0.56
Mexico 0.26 0.42
Australia 0.23 0.38
Canada 0.17 0.37
United States (Auestad) 0.12 0.51
South Africa (rural) 0.10 1.00
0.5
0.2
Recommen
ded
Ran
gefor Term
Form
ula
*mg/100 kcalAdapted from:1.Koletzko B, et al. J Perinat Med 2008;36:5‐14. 2.Kris‐Etherton PM, et al. J Am Diet Assoc 2007;107:1599‐611.3.Koletzko B, et al. Acta Paediatr 2001;90:460‐4.4.Simopoulos AP, et al. J Am Coll Nutr 1999;18:487‐9.5.The British Nutrition Foundation. Unsaturated Fatty Acids: Nutritional and physiological significance. London: Chapman & Hall; 1992:152‐63.6.Agostoni C, et al. J Pediatr Gastr Nutr 2010;50:1‐9.
Expert Positions for DHA and ARA Levels in Term and Preterm Infant Formulas
Term(% fatty acids)
Preterm(% fatty acids)
DHA ARA DHA ARA
World Assoc. of Perinatal Med./Early Nutrition Academy/Child Health Foundation (2008)1
0.2–0.5 ≥0.2 ‐ ‐
American Dietetic Association (ADA) and Dietitians of Canada (DC) position (2007)2
≥0.2 ≥0.2 ‐ ‐
Child Health Foundation, Germany (2001)3 ≥0.2 ≥0.35 ≥0.35 ≥0.4
Expert panel convened by ISSFAL (1999)4 ~0.35 ~0.5 ~0.35 ~0.5
British Nutrition Foundation (1992)5 ~0.4 ~0.4 ~0.4 ~0.4
ESPGHAN Committee on Nutrition (2010)6 ‐ ‐ 11 – 27* 16 – 39*
DHA Omega‐3 Dietary Sources
www.ars.usda.gov/main/site_main.htm?modecode=12354500
DHA Omega‐3 Dietary Sources
Food DHA (mg)
Milk (250 mL, DHA enriched) Up to 20 mg
Egg (Omega‐3) Up to 125 mg
Salmon (85 g or 3 oz, Coho, wild) 559
Salmon (85 g or 3 oz, Atlantic, farmed) 1238
Shrimp (12, large, steamed) 96
Sole (85 g or 3 oz, cooked) 219
Cod (85 g or 3 oz, Atlantic, cooked) 131
Health Canada Advisories on Fish Intake for Women Who Are or Might Become Pregnant,or Who Are Breastfeeding
1. Health Canada. Mercury in Fish: Consumption Advice. Available at: www.hc‐sc.gc.ca/fn‐an/securit/chem‐chim/environ/mercur/cons‐adv‐etud_e.html. Accessed July 20, 2010.
2. Health Canada Media Release (Feb 14, 2007). Health Canada advises specific groups to limit their consumption of canned albacore tuna. Available at: www.hc‐sc.gc.ca/ahc‐asc/media/advisories‐avis/_2007/2007_14‐‐e.php. Accessed July 20, 2010.
Types of fish to eat less often Types of fish to choose
High mercury, predatory fish
• Shark
• Swordfish• Fresh/frozen tuna
• Marlin
• Orange roughy
• Escolar
Other fish low in mercury & high in omega‐3 fatty
acids
•Salmon •Herring
•Shrimp
•Char
•Atlantic mackerel•Rainbow trout
•Canned light tuna (skipjack, yellowfin, tongol)
Limit to 150 g / month1 Consume at least 150 g (2 Canada’s Food Guide
servings) per week1
Check provincial & local advisories about the safety of fish caught locally.
Consumption of canned (white) albacore tuna should be restricted to no more than 300 g (4 Canada’s Food Guide servings) per week, but no restrictions on other types of
canned light tuna2
Formula with PDX/GOS Was Not Significantly Different From Controls in Bifidobacteria Stool Counts at 60 days When Analyzed by FISH (Primary Outcome)
* Significantly different from control formula and PDX/GOS formulaAdapted from Scalabrin DM, et al. J Pediatr Gastroenterol Nutr 2012;54(3):343‐52.
*
*
12
10
8
6
4
2
0Baseline 60‐Days
Stool BifidibacteriaCounts
(log 1
0CFU
/g stool)
Control Formula BreastfedPrebiotic Formula
Formula with PDX/GOS Has Bifidogenic Effect When Analyzed by qPCR (Secondary Outcome)
Measured by qPCRAdapted from Scalabrin DM, et al. J Pediatr Gastroenterol Nutr 2012;54(3):343‐52.
10
8
6
4
2Baseline 60‐Days
Bifidibacterium spp.
(med
ian log 1
0CFU
/g stool)
NSP=0.025
P=0.033
P=0.002NS
P=0.001
Formula withoutprebiotics
Breast MilkFormula with GOS /polydextrose
Formula with PDX/GOS Has Stool Softening Effect (Secondary Outcome)
Differences were significantly different during each time period. Adapted from Scalabrin DM, et al. J Pediatr Gastroenterol Nutr 2012;54(3):343‐52.
5
4
3
2
11 to 15 16 to 30 31 to 45 46 +
Watery
Loose
Formed
Soft
Hard
Study period, days
Stool consisten
cy
Breastfed
Control Formula
Formula with PDX/GOS
Human Milk Oligosaccharides
Content/Composition– 3rd largest component (5‐10 g/L mature
milk)1,2
– More than 200 human milk oligosaccharides identified (evidence for >900)2
– Variation due to maternal genetics, lactation stage3
Properties/Functions– Structurally diverse; variable composition– Digestion resistance; local and systemic
effects1
– Prebiotic – stimulates beneficial GI microbiota– Decoy receptors – toxins, pathogens1. Bode L. J Nutr 2006;136:2127‐30.
2. Ninonuevo MR, et al. J Agric Food Chem. 2006;54:7471‐80.3. Chaturvedi P, et al. Glycobiol.2001;11:365‐72.
Functions of Oligosaccharides
Prebiotics have special roles in maintaining the GI barrier and GI immune homeostasis
Oligosaccharides found in human milk:
– Are more complex than those found in the milk of other mammals1
– Are the most effective known prebiotics1
– Preferentially support the growth of bifidobacteria2
Prebiotics added to infant formulas may have clinical benefits, including lower incidence of diarrhea and acute respiratory infection3‐5
1. Kunz C, et al. Annu Rev Nutr 2000;20:699‐722.2. Zivkovic AM, et al. Proc Natl Acad Sci U S A 2011;108 Suppl 1:4653‐8.3. Arslanoglu S, et al. J Nutr 2007;137:2420‐4.4. Bruzzese E, et al. Clin Nutr 2009;28:156‐61.5. Waligora‐Dupriet AJ, et al. Int J Food Microbiol 2007;113:108‐13.
Criteria for Prebiotic Classification:
1. Resistance to gastric acid, enzyme hydrolysis and intestinal absorption
2. Fermentation by intestinal microflora
3. Selective stimulation of growth
(i.e., bifidogenic effect) and/or activity of intestinal bacteria that contribute to health
Gibson GR, et al. Nutr Res Rev 2004;17:257‐9.
Canadian Recommendations for Vitamin D Intake
Age group Recommended
Dietary Allowance (RDA) per day
Tolerable Upper Intake Level (UL) per
day
Infants 0‐6 months 400 IU (10 mcg)* 1000 IU (25 mcg)
Infants 7‐12 months 400 IU (10 mcg)* 1500 IU (38 mcg)
Children 1‐3 years 600 IU (15 mcg) 2500 IU (63 mcg)
Children 4‐8 years 600 IU (15 mcg) 3000 IU (75 mcg)
Children and adults9‐70 years
600 IU (15 mcg) 4000 IU (100 mcg)
Adults > 70 years 800 IU (20 mcg) 4000 IU (100 mcg)
Pregnancy & lactation
600 IU (15 mcg) 4000 IU (100 mcg)
*Adequate Intake rather than Recommended Dietary Allowance.Health Canada: Vitamin D and Calcium: Updated Dietary Reference Intakes. Accessed on‐line April, 2012. www.hc‐sc.gc.ca