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? 23_7_20 _7_2011 11
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?
Disability Offenders/ oxidative Stress Early survivors Substanceabuse schizophrenia Life Events mis Nutrition ADHD/autism dementia Fears/anxiety/ Multiple sclerosis depression Obese/STC VitD deficiency Microbiome - Allergy Metabolic Immune syndrome AI -type I EntericNS IBD Complex IBD Cance cer r ; testicula icular
Microbiome Allergy -immune EntericNS Autoimmune type I diabetes/coeliac Cancer : IBD testicular ? thyroid Round J Nature Reviews immunology2009 313 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 Patel, R, Lin P, Gut Microbes 2010 1;3, activation to CNS 186 Bercik P Gut 2011
An oral supplement or food product that contains a sufficient number of viable organisms (to alter the micr crof oflor 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 D Thomas COM OMMEN MENSAL SALS S – marker ker of Micr crobio biome me health 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 obact 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 3 rd 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 or 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? ons? 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 +/-
NEC 2 2 sepsis is or 3 3 1vs 10 Bin Nun 145 45 LBifidu ifidum 31 1 vs vs 24 Pediatrics Deshpande 2010 2005 <1500g STh Therm erm contro Israel BInfan nfantis is Cochrane Alfaleh 2011 l 2 vs Lin 2005 367 67<150 ATC TCC 22 vs 36 Taiwan 0g L L 10 (survive acido idophil phil .7d) us us B infan antis is 4 vs Lin 2008 460 60 L 40 0 vs vs 24 Taiwan <1500g acidophil 14 us Bbifidus BLF +LGG 0 vs Manzoni 304 04 less 7 vs 29 2009 than 10 Italy 1500g GA 39W Deshpande 2010,Alfaleh 2011
3 vs 8 Bin Nun 145 2005 <1500g Israel 7 vs 20 Lin 2005 367<1500g (survive Taiwan .7d) 2 vs 9 NS Lin 2008 460 <1500g Taiwan 304 less than 1500g 6 vs 12 Manzoni 2009 Italy
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 of 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 ors
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 outcomes 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, opment, chroni nic c diseas ase. e. Diet rec ecorded, orded, then en probi bioti tic Think nk about ut appli lication ations deve velopi oping 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 or RWH H Founda undati tion RWH H Angi gior ANZ NZ TRUST UST Chelsea helsea Webster er MERCY CY Pfizer er
New w South uth Wales es Royal yal North h Shore ore Hospit ital al John Sinn, Yvette Sheehy Joh ohn Hunter nter Hospital pital Ian Wright Javeed Travadi, Roslyn Black Royal oyal Prince 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
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