Co Coll llaborat ratio ion n of nu f nutri ritio iona nal l - - PowerPoint PPT Presentation

23_7_20 _7_2011 11

Jacinta M Tobin -2011 CAPGAN

Co Coll llaborat ratio ion n of nu f nutri ritio iona nal l in intake ke and pro robio iotic ic execu cuto tors rs in in in infa fants; ; re responsi nsibi bili lity ty fo for a r a li life fetime ime?

 Changing paediatric practice developed

world

 Increased allergy autoimmune neuropsych  Metabolic, cardiovascular chronic RD cancer  Premature infant  Probiotics not just the lactose fermenters  Specific conditions NEC Sepsis  Human- strain effects  Trial and future

Associated with changes in many environmental factors including lifestyle (hygiene, foods, increased indoor life) and advances in immunization, antibiotics and emergency practices,

 paediatricians are spending less time on

infectious diseases, but

 more time on complex, poorly understood

and hard-to to-tre treat at chronic ic condit itio ions, ns, with

 profound effects on quality of life for

patients and families, persis ist into adulthood



Mechanism(s) anism(s) p pre reve vent? nt?

• xidative

StressEarly Life Events



Disability survivors Offenders/ Substanceabuse schizophrenia

misNutrition

ADHD/autism dementia



Fears/anxiety/ depression Multiple sclerosis

Microbiome -

Obese/STC VitD deficiency

Immune EntericNS

Allergy AI -type I IBD Metabolic syndrome Complex IBD

Cance cer r ; testicula icular

Microbiome

• immune

EntericNS

Round J Nature Reviews immunology2009 313

Allergy Autoimmune type I diabetes/coeliac IBD Cancer : testicular ? thyroid colorectal

 Infant exposed in utero to microbes/other via

amniotic fluid=Mother and her surrounds

 Immunoglobulin transfer mother to infant  Mode of delivery –vaginal sample of maternal

vaginal and colonic flora, casesarian NOT – decrease lactobacillus &bifidobacterium spp

 Feeding-mothers milk-bact/macrophages  Interaction withTLR’s commensals

nsals diff to pathogen hogens, s, TJ and anti-microbial peptide, nutritional s…cytoprotect, epithelial cell proli liferation, feration, secretion -Sensing sing by ENS vagal activation to CNS

Patel, R, Lin P, Gut Microbes 2010 1;3, 186 Bercik P Gut 2011

 An oral supplement or food product that contains a

sufficient number of viable organisms (to alter the micr crof

• flor

lora a of the host*) AND has the potential to deliver health benefits =mimic commensals Food and Agriculture WHO 2001 Genera: lactobaccillus, bifidobacterium, streptococcus –fermentive anaerobes Metchnikoff 1907, Yakult 1935,1965

 (prebiotic =a non digestible food ingredient that

benefits the host by selectively stimulating the favorable growth or activity if 1or other indigenous probiotic bacteria eg oligosaccharides nucleotides breast st milk ) >>>SOL OLUTI TION??subset ON??subset of COM OMMEN MENSAL SALS S –marker ker of Micr crobio biome me health

D Thomas Pediatrics 2010 126 p1217

 In necrotiz

izing ng enteroco coliti itis, s,10% 0% <1500g

 Prem, enteral fe

feeding fo formula, , inappropri priat ate e proinfl nflam ammatory tory response e and bacterial l coloniza nizatio tion

 80% of 400 plus microbes are unculturable –need

molecular methods

 Bacterial DNA amplified, Terminal restriction

fragment length polymorphism( T_RFLPa)nalysis and library sequencing

 Decrease

sed d diversit ity y and increased d abundance nce of f proteoba

• bact

cteri ria a in NEC aff ffected infa fants. . NEC more similar r than twins

Wang Y ISME J 2010 3 * 944

 1.All infants born in Norway 1999-2000 464

(99.6%) enrolled<1000g <28 weeks after day 6

 Low rate sepsis 19.8%  Coagulase neg enterococci 47% Mort 10% and

candida mort 43%

 Feeding by day 3 human milk (98%) FEF 170-180

mL/kg by 3rd week Ro Ronnestad tad A P Pediatri trics cs 20 2005 05

 2.

• 2. Colonisa

isatio tion n with Gram negative ive baci cilli i gen entami tamicin cin res esistan tant t pred edicts cts gen entamic amicin n res esista tant nt Gneg g sepsis s in VLBW infants nts 20 2004 04-20 2007 07 ( (New York) k)

 Smith A Pediatric Infectious diseases J 2010

 Barclay 2007 Deshpande 2010 Pediatrics

Alfaleh 2011Cochrane review

 Pr

Probio bioti tics cs reduc uce e NEC 2 o

• r 3 RR 0.35

 All cause

e mortali lity ty RR 0.4 Products, Condition, BUT …..

 Let look at some of the majo

jor studi dies es cited- seps psis is and NEC effects ts in differe erent nt directi tions?

• ns?

 Chang

ange e produ duct t change ge outcome? e?

 Chang

anges es ove ver time 1997 +evi vidence ence decreas reasing ng NEC incidence ence wi with increas asing ng standards andards eg g fresh h breast ast milk?sepsis sepsis +/-

Deshpande 2010,Alfaleh 2011

 Pediatrics Deshpande 2010  Cochrane Alfaleh 2011

NEC 2 2

• r 3

3 sepsis is

Bin Nun 2005 Israel 145 45 <1500g LBifidu ifidum STh Therm erm BInfan nfantis is

1vs 10 contro l

31 1 vs vs 24 Lin 2005 Taiwan 367 67<150 0g (survive .7d) ATC TCC L L acido idophil phil us us B infan antis is

2 vs 10

22 vs 36 Lin 2008 Taiwan 460 60 <1500g L acidophil us Bbifidus

4 vs 14

40 0 vs vs 24 Manzoni 2009 Italy 304 04 less than 1500g GA 39W BLF +LGG 0 vs

10

7 vs 29

Bin Nun 2005 Israel 145 <1500g

3 vs 8

Lin 2005 Taiwan 367<1500g (survive .7d)

7 vs 20

Lin 2008 Taiwan 460 <1500g

2 vs 9 NS

Manzoni 2009 Italy 304 less than 1500g 6 vs 12

 Optimal health of mother prenatally nutrition

exercise D and microbiome

 Optimal care of pre-iminent preterm delivery

including transfer

 Optimal care peri-partum prompt treatment

• f sepsis early feeding with human

man mi milk

 Care with fortifiers in early weeks pp  Optimal Home care Breast feeding, Home –

family happy (not depressed) adequate resources and education probi bioti tics cs execut utors

• rs

 2006 Infloran or ABC

BC Dophi hilus lus Infant ant Po Powd wder r

 Po

Powe wer r calculation ation and regi gist ster er wi with trials s reg egist istry ry

 Verify –strains confirm Tissue Register and

quantify

 Culture for contamination  transport

Victorian ian trial commenc nced ed October er 2007

 11

1100 00 infants nts <15 1500 00g g OR < R <32 32 we week eks s Incidence idence of LOSepsis epsis and range of secondary

• utcomes NEC death and followup 12m

.now expanded to 2 states and NZ

Respons ponsibi ibili lity ty Info formed rmed parents ents

 Study nurses and neonatologists CRF  Trial co-ordinator  Statistician Susan Donath  DMSC

SC decided ed 100, 200 400 and 700 infants nts Neonatologist

 Infectious diseases  Clinical trials infectious diseases

 Respons

ponsibi ibili lity ty :Listing :Pharmacological Standards Europe Health Canada submission to FDA August 2010. Companies will need incentives and assistance $Price up

 Identi

entity ty regi gist ster ered. ed.

 Pr

Probio bioti tic activi vity

 Route of admin, Dosage and form  Use or purpose evidence  Cautions adverse events

 Product factors of reliability; strain-subtype, registry

at tissue bank, the supply chain, the ability to test for quality and contamination in batches will remain concerning,

 Clinicians recommending a probiotic should apply

the same principles and standards that apply to other forms of therapeutics, understanding the specificity and stacking up the strain-specific data from adequately powered randomized controlled trials including our study.

Regi gistry try for long g term followu wup p allergy gy AI cancer ers, s, deve velopment,

• pment, chroni

nic c diseas ase.

• e. Diet

rec ecorded,

• rded, then

en probi bioti tic Think nk about ut appli lication ations deve velopi

• ping

ng wo world set etti tings ngs optimal mal reg egimens mens (?post post diarrhoe rrhoea a rehabil habilitation tation but nutrit rition ion first ) appli licatio cations ns for pre-pre pregnant gnant , pregnant gnant and infant nt

Sue ue Jaco cobs bs Suza zanne e Garlan and Marie ie Pirotta ta Sepeh pehr Tabrizi izi Gilli lian an Opie Kennet nneth h Tan n Monash nash

Nurses Kristy y Elsayed, Emma Yeomans ans

Mimi mi Tang ng Barry y Kiely y (Irelan land) Solga lgar Inc Lyndh dhurs urst t USA Coli lin Morley ley NHMR MRC Lin n Ung Study dy co-ordin dinat ator

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RWH H Chelsea helsea Webster er MERCY CY RWH H Founda undati tion Angi gior ANZ NZ TRUST UST Pfizer er

 New

w South uth Wales es Royal yal North h Shore

• re Hospit

ital al

 John Sinn, Yvette Sheehy  Joh

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nter Hospital pital

 Ian Wright Javeed Travadi, Roslyn Black  Royal

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ce Alfred d Hospit ital al

 David Osborn, Shelley Reid  Tasm

sman ania ia Royal yal Hobart bart Hospit pital al

 Tony De Paoli, Karen Butterley  New Zealand Christchurch Women’s Hospital  Brian Darlow Nicola Austin, Nicki McNeill, Trish Graham  Auc

ucklan kland d City ty Hospit pital al

 Jane Alsweiler/Mariam Buksh, Jodie Daculan