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Human Breast Milk. พญ.วรางค์ทิพย์ คูวุฒยากร หน่วยทารกแรกเกิด ภาควิชากุมารเวชศาสตร์ คณะแพทยศาสตร์ มหาวิทยาลัยเชียงใหม่. Questions. Why breast milk is the best? How milk is produced ? What are human breast milk compositions? Does it different from cow’s milk? - PowerPoint PPT Presentation
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พญ.วรางค์�ทิพย์� ค์ ว�ฒย์ากรหน่�วย์ทิารกแรกเกด ภาค์วชาก�มารเวชศาสตร�
ค์ณะแพทิย์ศาสตร� มหาวทิย์าลั ย์เช!ย์งใหม�
Questions
Why breast milk is the best?How milk is produced ?What are human breast milk compositions?Does it different from cow’s milk?What are protective components in human breast
milk?
Effect of breastfeeding on the mothers
Decrease postpartum hemorrhageDecrease breast , ovarian and endometrial cancerDecrease osteoporosisMore rapid return to pre-pregnancy weight
Decrease infection in childrenDiarrhea ถ่�าย์เหลัวRespiratory tract infection ตดเช$%อทิางเดน่หาย์ใจOtitis media ห ช %น่กลัางอ กเสบBacteremia ตดเช$%อแบค์ทิ!เร!ย์ใน่
กระแสเลั$อดBacterial meningitis เย์$)อห�*มสมองอ กเสบจาก
แบค์ทิ!เร!ย์Urinary tract infection ตดเช$%อทิางเดน่ปั,สสาวะ Late onset sepsis in ตดเช$%อใน่กระแสเลั$อดpreterm infant ใน่ทิารกก�อน่ก-าหน่ดNecrotizing Enterocolitis ลั-าไส*เน่�าเปั/) อย์
from AAP.Breast feeding and the use of human milk:Pediatrics.2005;115(2):506
from American Academy of Pediatrics. Breast feeding and the use of human milk:Pediatrics.2005;115(2):506
Decrease non-infectious diseaseAsthma หอบห$ดOverweight and obesity โรค์อ*วน่Insulin dependent DM (type I) เบาหวาน่Non insulin dependent DM (type II)เบาหวาน่Hypercholesterolemia ไขม น่ส งLymphoma มะเร2งต�อมน่-%าเหลั$องLeukemia มะเร2งเม2ดเลั$อดขาวHodgkin disease มะเร2งต�อมน่-%าเหลั$องSudden Infant Death Syndrome (SIDs)
from American Academy of Pediatrics. Breast feeding and the use of human milk:Pediatrics.2005;115(2):506
Neurodevelopment
Anderson JW, Johnstone BM, Remley DT, 1999 Meta-analysis 20 studiesSignificantly higher levels of cognitive function were seen in
breast-fed than in formula-fed children at 6–23 mo of agesHigher IQ 3.16 points in term (95%CI 2.15,3.17)Higher IQ 5.18 points in preterm (95%CI 3.59,6.77)
American Journal of Clinical Nutrition, Vol. 70, No. 4, 525-535, October 1999
WHO and UNICEF1. Infants should be exclusively breastfed for the first six
months of life to achieve optimal growth, development and health
2. Infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to two years of age or beyond.
“กิ�นนมแม�เพียงอย�างเดียวจนถึ�งอาย� 6 เดี�อน หลั�งจากิน��นกิ�นนมแม�ควบค��กิ�บอาหาร
เสร�ม จนถึ�งอาย� 2 ปี หร�อมากิกิว�า “http://www.who.int/nutrition/topics/infantfeeding_recommendation/en/index.html
Contraindications to breastfeeding
HIV positive motherHTLV type I and II positiveActive tuberculosis diseaseHerpes simplex infection on a breast Drugs of abuse Expose to radioactive materialsReceiving diagnostic or therapeutic
radioactive isotropesReceiving antimetabolites or
chemotherapeutic agentsAAP.Breast feeding and the use of human milk:Pediatrics.2005;115(2):506
American Academy of Pediatrics .Breast feeding and the use of human milk. Pediatrics 2005;115(2):506
Exclusive breastfeeding
is defined as no other food or drink, not even water, except breast milk (including milk expressed or from a wet nurse) for 6 months of life, but allows the infant to receive ORS, drops and syrups (vitamins, minerals and medicines).
ให*ทิารกกน่น่มแม�อย์�างเด!ย์วโดย์ไม�ให*อาหารอ$)น่ๆแม*แต�น่-%า เปั4น่ระย์ะเวลัา 6 เด$อน่
ย์กเว*น่น่-%าเกลั$อแร� ย์า หร$อ วตามน่เสรม
5.0
19.0
31.034.048.0
60.065.0
0
40
80
เกิาหลัพี.ศ.2547
เขมรพี.ศ.2548
จนพี.ศ.2548
ฟิ$ลั�ปีปี$นส%พี.ศ.2546
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แหลั�งท)มา : ส*าน�กินโยบายแลัะย�ทธศาสติร% กิระทรวงสาธารณส�ข
ร/อยลัะ
Thai Breastfeeding Center Foundation 2012
เปีรยบเทยบกิ�บท�)วโลักิ เปีรยบเทยบกิ�บท�)วโลักิ อ�ติรากิารเลั�ยงลั�กิดี/วยนมแม�อย�างเดียว อ�ติรากิารเลั�ยงลั�กิดี/วยนมแม�อย�างเดียว 6 6 เดี�อนเดี�อนปีระเทศไทยจ�ดีอย��ในกิลั��มท)มอ�ติราน/อยกิว�าร/อยลัะปีระเทศไทยจ�ดีอย��ในกิลั��มท)มอ�ติราน/อยกิว�าร/อยลัะ
20 20 ((สแดีงสแดีง))
Anatomy of the breast
Anatomy of the breast
The Lactation
cycle
Mature
Pregnancy
Involution
Lactation
Pubertal development
EmbryogenesisGH, estrogen
progesterone, prolactin, HPL
Prolactin, oxytocin
progesterone, prolactin, HPL
progesterone
Lactogenesis I & II
Lactogenesis II- Prolactin
Anatomy of the breast
Lactogenesis II- Oxytocin
Cellular mechanisms for milk synthesis and secretion
1. Exocytosis Most of the components of the aqueous
fraction eg. Protein- casein, CHO- lactose
2. Fat synthesis and secretion3. Transport across apical membrane
Ions and water4. Transcytosis of interstitial molecules
Immunoglobulin A5. Paracellular pathway
The pathway of milk synthesis and secretion
Colostrums, transitional and mature milkColostrums
1-4 day after parturitionTransitional milk
4-10 days after parturitionMature milk
After 10 days
Colostrums, transitional and mature breast milk
Figure 1: Composition of colostrum, transistional and mature milk
0%
20%
40%
60%
80%
100%
colo
stru
m
transi
tiona
l
mat
ure
w ater
fat
lactose
protein
Colostrums ingredients
Composition of breastmilk
Carbohydrate in human milk
Mainly carbohydrate is lactoseIncreasing amount correlate with milk volumeProvides galactose
A sugar involved in brain and nervous system developmentLow risk of causing dental caries
Fat in human milk30-50 g/L, 97-98% is triglycerideMajor energy for a baby (45-55% of total calories)Synthesis and development of retinal and neural tissuesEssential fatty acid (FAs)
Linoleic acid (8-17%) α-Linolenic acid (0.5-1.0%) Arachinodic acid (0.5-0.7%) (LC-PUFA) Docosahexaenoic acid (0.2-0.5%) (LC-PUFA)
Fat digestion is aids by gastric lipase and bile-salt dependent lipase in human milk
Factors influencing human fat content and composition
Factor
Duration of gestation
Stage of lactation
Parity
volume
feeding
Maternal diet
Maternal energy status
Influence
BM of the mother who deliver preterm infant has more LC-PUFAs
PL and Cholesterol are highest in early lactation
High parity is associated with reduced endogenous FA synthesis
High volume is associated with low milk fat content
Human milk fat content progressively increases during a single nursing
A diet low in fat increase endogenous synthesis of MC-FA
High weight gain in pregnancy is associated with increased milk fat
Foremilk vs Hindmilk
Protein in Human milk 15.8 g/L (colostrums) 9.0 g/L (mature milk) Whey : Casein = 60 :40 Total protein
Protein nitrogen Non-protein nitrogen (20-25%)
free amino acid, Carnitine, taurine, Aminosugars
Nucleic acids, nucleotides Polyamines
Human milk protein functions
Growth Protective factors Carries for vitamins and hormones Enzyme activities Biological activities
Vitamins in human milkCorresponding to maternal statusFat soluble vitamins
Vitamin A (200-300 mg/L)Decreases with advancing lactation
Vitamin D (0.1-1.0 ug/L)Maternal intake, sunlight, northern latitudesSupplement vitamin D 10 ug/L is
recommended in a baby at risk
Fat-Soluble vitaminsVitamin K (1-9 ug/L)
Tran placental transfer is minorMaternal dietary intake bears little relationship
to milk vitamin K contentMaternal supplementation of 5-20 mg/day
increases in milk and infant plasma levels
Water-Soluble vitaminsVitamin C (100 mg/L)
8-10 fold higher than the maternal plasma concentration
Vitamin B6
Low levels in mothers with a long-term history of OCT uses
Water-Soluble vitaminsVitamin B12
Vitamin B12 deficiency was found in infants nursed by mothers who were strict vegetarians
FolateInterfere by maternal diet and medication
Minerals and trace elements in human milkNot correlate with amounts in the maternal diet or
maternal serumCalcium, phosphorus and magnesiumSodium, potassium and chlorideIron (0.3mg/L), copper and zinc
Iron from HM is absorbed 5-fold more efficientlyLactoferrin
Immunomodulating agentAffect the development of newborns’ immune systemcytokinesEnhance inflammation
TNF-α, IL-1, IL-6, IL-8, interferon-γSuppress inflammation
IL-10Soluble receptors
TNF-α1, TNF-α2
Anti-inflammatory componentsAntioxidants: vitamins A, C, E Enzymes : catalase, glutathione peroxidaseE prostaglandinsEnzymes inhibitors: Platelet Activating Factor (PAF)Protease inhibitorAnti-inflammatory cytokine: IL-10
Hormones and growth factorsHigher in early mammary secretion (colostrum)Some hormones are synthesized in mammary cells, transfer
from maternal circulation or modified by mammary cellsMammary synthesis : PRL, GnRH, thyroxine(T4),
Triiodothyronine(T3), PTH-rP, estrogenTransfer from maternal circulation : TRH, progesteroneModified by mammary cell : increase resistance to
digestion in infants’ GI tract : PRLGrowth factors stimulate GI growth in the newborn
Enzymes in human milkProtective function
LysozymePeroxidaseAntiprotease, catalase, glutathione peroxidase, PAF-acetylhydrolase
Digestive functionAmylaseBile salt-stimulate lipase
Component Human milk Bovine milk
Carbohydrate (g/dL)•Lactose•Oligosaccharides
7.3 1.2
4.0 0.1
Protein (g/dL)•Caseins•α-lactalbumin•Lactoferrin•Secretory IgA•β-lactoglobulin
0.2 0.20.20.20
2.60.2
TraceTrace
0.5
Lipids (%)•Triglycerides•Phospholipids
4.00.04
4.00.04
From Neville MC.Physiology of lactation.Clin Perinatol1999;26:257
Component Human milk Bovine milk
Minerals and others(nM)•Sodium•Potassium•Chloride•Calcium•Magnesium•Phosphate•Bicarbonate
5.015.015.07.51.41.86.0
154324305115
From Neville MC.Physiology of lactation.Clin Perinatol1999;26:257
Protective nutrients in human milkNutrients Amount Function
Protein•sIgA•IgM•IgG•Lactoferrin
•Lysozyme•α-lactalbumin
•casein
50-100 mg/dl2 mg/dl1 mg/dl100-300 mg/dl
5-25 mg/dl200-300 mg/dl
200-300 mg/dl
Immune protectionImmune protectionImmune protectionAnti-infective, iron carrierAnti-infectiveIron carrier (Ca2+), part of lactose synthaseIron carrier, inhibit microbial adhesion to mucosal membrane
Protective nutrients in human milkNutrients Amount Function
Carbohydrate• Lactose•Oligosaccharides•Glycoconjugates
6.5-7.3 g/L1.0-1.5 g/L-
Energy sourceMicrobial ligandsMicrobial and viral ligands
Fat•Triglyceride•LC-PUFA
•FFA
3.5-4.5 g/L-
-
Energy sourceEssential for brain and retinal development and for infant growthAnti-infective
Immune protectionSIgA – secretory immunoglobulin A is the main
component Protects mucosal surfaces eg digestive and
respiratory tractComposed of specific antibodies against bacteria
that mother has encountered in the environmentIncludes specific antibodies against diarrhea:
giardia, toxigenic E coli, Vibrios, Campylobacter
Enteromammary Immune system
Secretary IgA
Secretary IgA
Non immune protectionBroad spectrum of anti-infective activityLactoferrin
Single-chain glycosylated protein692-amino-acid79 -kD
neutrophil
macrophage
Lactoferrin
Airway Epithelium
Respiratory
Tract
CD14-TLR4 complex
LPSAnti-Inflammatory
Bacterial KillingPseudomonas
Pseudomonas BiofilmAnti-Biofilm
HIV, CMV
Anti-Viral
Candida
Fungicidal
Rogan et al. Respiratory Research 2006 7:29
Lysozyme130-amino-acid-
containing glycoprotein
Hydrolyzes the 1-4 linkage between N-acetyl glucosamine and N-acetylmuramic acid
Lyses mostly gram positive and few gram negative bacteria
Increases with prolong lactation
K-caseinAntiadhesive
H. pylori, S. pneumoniae, H. influenzae
Casein macropeptideStrong growth
promoting factor for B. bifidum
α-lactalbuminImportant whey protein in BM3 polypeptide fragments were recently found to have
antimicrobial activityThese peptides are generated after exposure to
protease in GI tractE.coli, K. pneumoniae, S. aureus, S. spidermidis
C.albican
Glycoconjugates and oligosaccharidesStructure Distribution in
milkFunction
Oligosaccharides
Skim milk Protect against heat stable E.coli enterotoxin, attachment of H.influenzae and S.pneumoniae to respiratory epithelium, v.cholerae hemagglutinin activity
Glycoproteins•Mucin•Lactadherin
MFGM/ skim milkMFGMMFGM/skim milk
Prevent binding of V.choleraePrevent binding of S.fimbriated E.coli Prevent binding of Rotavirus
Gangliosides MFGM Receptor analogs for heat labile toxin of V.cholerae and E.coli
Glycosaminoglycan
MFGM Inhibits binding of HIV gp 120 to CD4 receptors
How oligosaccharides block attachment of bacteria to epithelial cells
Lipid
Milk fat globules protect infants from infection byThe membrane glycoconjugates acts as specific
bacteria and viral ligandsFFA have a detergent like lytic action on enveloped
viruses (HIV, HSV type I), bacteria , fungi and protozoa
Comparison human & cow’s milk