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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).

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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