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What does allergy prevention,

constipation, colic and mastitis

have in common

A/Professor John Sinn

MBBS (Syd), D Paed, DCH, M Med(Clin Epi), FRACP

Consultant Neonatologist and Infant Allergist

The Paediatric Centre, St LeonardsThe University of Sydney

The Children’s Hospital, Westmead

Royal North Shore Hospital

Man/ Woman’s best friend: 3000 cohort study in Melbourne

Less allergies if have dog inside house p 0.043 compared

to outside p 0.66

More siblings the less allergy

Probiotics

Produce lactic acid- lowers the pH of intestines and inhibiting bacterial villains such as Clostridium, Salmonella, Shigella, E. coli, etc.

Aid absorption of minerals, esp Ca, increased intestinal acidity.

Production of β- D- galactosidase enzymes that break down lactose.

Produce vitamins (especially Vitamin B and vitamin K)

Act as barriers to prevent harmful bacteria from

colonizing the intestines

Gastric pH and Gut flora

Mice with antacid had higher IgE and immediate skin reactivity cf to without antacid

In Humans had a 25% increase of allergy associated with Antacid ingestion after 3 months

Proton pump inhibitors: causes more pathogenic organism: Salmonella, Clostridia

Bavishi, DuPont: AP&T 2011;34 (11-12), p1269-1281

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Microbiome LSCS vs NVD

Vagina: lactobacillus, provotella, sneathia

LSCS: is hospital organism Staph and C Difficule

Lower bifidobacterium in neonate and lower bacteria

diversity

High fat diet affects the intestinal microbiome

Increase non pathogenic campylobacter in the infant

Kaplan-Meier analysis of cumulative incidence of chronic asthma.

Roduit C et al. Thorax 2009;64:107-113

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.

Caesarian vs Normal vaginal delivery and

Asthma Rates

Immuno-modulation factors:

Potential Good Bugs

Lactobacillus GG or Rhamnosus

Allergy prevention

L. Reuteri

Colic

L. Fermentus / Salivarius

Mastitis

L. paracasei: obesity

B. Breve Breast milk probiotic, allergy

Infloran: L. acidophillis /B. Bifidum: NEC

PROPREM: ABC: B Infantis, S. thermaphilus, B lactis: NEC

Saccharomyces boulardii, L.acidophilus and B bifidum: Diarrhoea

Probiotic versus no probiotic:

Infant eczema: 13 trials, 1911 infants

Heterogeneity: P = 0.37; I² = 8%

Test for overall effect:

P = 0.001 RR 0.79, 95%CI 0.68, 0.91

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Soluble fibre

Can be a prebiotics

Some causes bloating and colic

eg FOS, inulin

Metamucil is a insoluble fibre (psyllium) is not a good

prebiotics and not recommended to kids < 13 yrs

Prebiotics are indigestable fibre

Benefibre is soluble and can be used after 1 year of age.

Is 100% wheat dextrin: is a prebiotic

Established PREbiotics Breast Milk oligosaccharides

Milk 20 gm/l in colostrum & 12- 14 gm/ in mature milk.

Polydextrose

Inulin Wheat, banana, onions, garlic, leek, chicory.

FOS (Fructo-oligosaccharides or oligofructose) plants.

GOS (Galacto-oligosaccharides) milk.

Lactulose

(Journal of the American Dietetic

Assosciatio,2008)

Short chain fatty acids (SCFAs) are the products of colonic bacterial degradation of unabsorbed starch

Acetate, Propionate, and Butyrate and Lactic acid.

Colonocyte (Proliferation / Differentiation)

& Function (Tight Colonic Junction

/ Inflammatory Suppression).

POSTbiotics

• SCFA facilitate absorption of water and electrolytes

• Acetate increases colonic blood flow and enhances ileal motility.

SCFA help improve Water & Electrolyte Absorption

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Butyrate

provides fuel for colonic epithelial cells,

Help heal

LOW Fiber Diet low SCFA

high occurrence of colonicdisorders.

SCFA support the critical

Gut mucosal barrier: Keeping Gut integrityPrebiotic versus no prebiotic:

Infant eczema incidence

4 trials, 1218 infants

RR = 0.68, 95% CI 0.48, 0.97; p=0.03

Heterogeneity: I2 = 34%

Adapted from Mihatsch WA et al. Acta Paediatrica 2006;95:843-8.

GIT transitional TimeStool consistency

Preterm infants

Antibiotic-associated Diarrhea

Systematic review: 9 RCT (2 in children):

60% reduction in duration of diarrhea compared with placebo (P<0.01) 2002

9/10 pediatric trials (different products) favored probiotics (RR 0.49; 95% CI 0.32 to 0.74).

Johnston BC. Cochrane Database Syst Rev, 2007

D’Souza et al. BMJ, 2002

Diarrhoea

Probiotics/ prebiotics,

Electrolyte

Lactose Intolerance. Reducing substance > 2% required

LF formula or Soy

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Probiotics: constipation

Meta-analysis of 5 RCTs (3 adults n = 266;

2 children,

n = 111

In children, L. casei rhamnosus Lcr35,

showed a beneficial effect.

but not L. rhamnosus GG,

Chmielewska A. World J Gastroenterol, 2010

ConstipationBreast milk less due to the prebiotics

Infant formula:

More whey

HA is 100% whey

Stage 1 has 60-70% whey

Stage 2 has 50-60% whey

Stage 3 has 20-30% whey

Probiotics: soften stools

Prebiotics: increase transient times

AR formula or thickener associated with constipation

Constipation: other treatment

Benefibre

Prune juice:

Paraffin

Movacol ‘iso-osmotic’ solution –Macrogol

Suppository:

Glycerine

microlax

Colic

22 studies

Benefit with hydrolysed formula

Benefit with maternal elimination diet

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Probiotics and colic: Systematic

review

3 trials

220 breast fed infants

L reuteri

Significant better compared to placebo

NNT 1:2

Anabree: 2013 BMC Pediatrics

Colic and irritable baby

HA: increase transit time

Probiotic: L reuteri

prebiotic formula

Cow milk intolerance

Proton pump inhibitor or H2 receptor

antagonist:

Simeticone Drops

RCT show no difference

Anti-Foaming agent silicon Dioxide and dimethylsioxane

C2H6)Si.Si02, Not metabolised, break gas bubbles

Decrease gas, antiflatulant

It has no reported adverse effects, and the simple act of being able to give their baby something may help parents cope better with the crying.

AntiflatulentBreastfed or bottle fed: Simeticone 40mg/ml oral suspension sugar freeGive one drop (0.5ml) before each feed. Increase to two drops (1ml) if required. Supply 50 ml.Age: under 6 months

Reflux

AR formula Casein dominant

Increase constipationWhey 100% less constipation

Thickener to breast milkNot use antacid as high Aluminium

content

Omega 3 and allergy prevention

Systematic review of polyunsaturated fatty acid supplementation in infancy for the prevention of allergy Schindler T1, Osborn DA2, Sinn J2

9 studies enrolling 2704 infants reported allergy outcomes. 2 years FU

All allergy: no difference (1 study, 323 infants; RR 0.96, 95% CI 0.73, 1.26),

asthma (3 studies, 1162 infants; RR 1.04, 95% CI 0.80, 1.35),

dermatitis/eczema (7 studies, 1906 infants; RR 0.93, 95% CI 0.82, 1.06)

food allergy (3 studies, 915 infants; RR 0.81, 95% CI 0.56, 1.19).

allergic rhinitis (2 studies, 594 infants; RR 0.47, 95% CI 0.23, 0.96).

2-5 years, meta-analyses found no difference in incidence or prevalence of all allergic disease, asthma, dermatitis/eczema, allergic rhinitis or food allergy.

Conclusions: no significant effect of higher infant PUFA intake on infant or childhood allergy, asthma, dermatitis/eczema or food allergy.

There is insufficient evidence to determine an effect on allergic rhinitis.

Vit D

Currently conflicting evidence of role of Vit D and

prevention of allergy.

Difficult to have RCT on this.

Supplementation decrease Atopic eczema and Asthma

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LEAP Study (Learning Early about Peanut allergy)

640 infants with severe eczema, egg allergy or both to

consume or avoid peanuts until 60months

From 4-11 months

Results: Peanut allergy at 60 months

Nut group 1.9% vs avoidance 13.7% ITT

Prevalence nut group 10.6% vs 35% in avoidance gp

Leap

1303 Breast fed infants UK

RCT: 3/12 vs 6/12 allergenic foods (peanuts, egg, CM, sesame, white fish and wheat)

Results: Early vs late

2.4% vs 7.3% food allergy

0 vs 2.5% peanut allergy 2g per week

No difference milk. sesame, fish, wheat

EAT

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Allergy Prevention CEFAL: Centre for Food & Allergy Research (NHMRC)

When your infant is ready at around 6 months but not before 4 months, start to introduce a variety of complementary foods, starting with iron rich foods, whilst continuing breastfeeding

All infants should be given allergenic solids foods including peanut paste, cooked egg and wheat products in the first year of life. This includes those at high risk of allergy

Hydrolysed (partially or extensively) infant formula are not recommended for prevention of allergic disease

Others:

Probiotics/ Prebiotics esp if interventions

Omega 3, Vit D

Importance oral exposure

Eg topical creams with any food oils and proteins

Breast feeding Mastitis

Dysbiosis

Single strain of pathogenic bacteria

Lactobacillus disappear

Most common organism is Staph Aureus, Staph Epi esp

chronic infection

L Fermentum

L Salivarius

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RCT n 352

A) L. fermentum CECT 5716 (n=127)

B) L. salivarius CECT 5713 (n=124)

C) Antibiotics (n=101)

Inclusion:

breast inflammation,

painful breastfeeding

milk bacterial count 14 log10 (CFU)/mL

milk leukocyte count 16 log10

cells/mL.

74 had fissures

:

Bacterial Count

Lactobacillus vs AntibioticsResults

Breast pain reduction similar between the 2 probiotics

Bactrim is the most effective

Augmentin is next

Amoxil and Flucluxacillin was less effective

88% Grp A L Fer and 85% Gp B L Sal complete recovery

Stop breast feeding and vaginal candidiasis only in antibiotic

Gp

Mechanism is related to probiotic stimulating the immune

system

Summary

Gut flora important to regulate the immune system not to

overreact and become allergic to food or aeroallergen

Ensuring good microbiome is the key for prevention of

allergy and also childhood infections

Breast Fed as long as possible

Infant formula with prebiotic or probiotics

Supplementation with probiotics during pregnancy,

lactation and to infant as per WAO

Obesity

High protein intake in infancy

Rapid weight gain in infancy

High energy intake

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Protein in Breast milk vs Formula

Higher protein intake proposed to play a role

14 – 16 g Protein/L

Protein

HypothesisProtein intake in excess

may lead to:

9 – 13 g Protein/L

Long-Term

Risk of obesity?

Weight gain Weight for Length

Short-Term

Insulin IGF-1

Circulating amino

acids

Term

Infant

Formula

Mature

Breast

Milk

Koletzko Germany, Poland, Belgium, Italy, Spain

1.7 to 2.2 g protein /100kcal Vs 2.9 and 4.4g

2yr follow up

323 higher protein 313 lower protein

298 breast fed control

Lower protein still higher weight increase compared to

breast milk

Formula fed intake 14 to 20g/d at 3 and 6 months

Breast fed 7g/d

Catch up growth

IUGR

postnatal catch up growth

increase central fat

Systematic review of 24 studies

Outcome: obesity at any age after infancy

Infants who grow more rapidly are increased

risk of obesity

OR = 1.35 to 9.38 times

Born from 1927 to 1994Baird J, et al. Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ.

2005 Oct 22;331(7522):929.

Dietary energy at 4/12

predict postnatal weight gain

and BMI SGA consume larger volumes than normal birth weight

Compensatory rapid postnatal weight gain

Associated with obesity

Ong et al Pediatric vol 117, 3, e503 2006

Summary: Prevention

Obesity Prevention Breast Feeding

Microbiota

Reduce Protein

Reduce excess Growth

Vit D

Allergy Prevention Breast feeding

Prebiotics/ probiotics

Vit D

Introduce allergens before 12 months

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Atopic eczema

Associated with high levels of IgE to

milk, egg and peanut

Egg is the most frequently involved allergen, followed by cows milk protein.

IgE antibodies have been implicated in most cases of cows milk protein- induced eczema, about 10% of cases are not IgE associated.

Sleep disturbances

For the severe eczema 35 % would benefit from Food elimination

Ideally do skin prick test on eczema children with a 45% chance of positive food response

CM protein induced enteropathy

Not IgE

Diarrhoea

Vomiting, irritability

80% respond to EHF

20% chance of cross reactivity to soy

Mx: mother avoid CMP. And soy initially.

Size of the molecule

Allergen 10000-70000 daltons

Intact Soy 28000 daltons

Partial hydrolysed 1100-10000 daltons

Extensive hydrolysed < 1500

Can be Allergenic if >1300 daltons

Amino acid < 1000 daltons

2 Human, 3 CM 4 Donkey

Natural history of food allergy

IgE-mediated allergy:- Egg 66% remit after 5 yrs- Peanut 20% may remit (8% may recur)- Treenut, seafood typically persist

Declining/low levels of specific-IgE predictive

Non-IgE-associated GI allergy food intolerance

- Infant forms resolve 1- 3 years- Toddler/adult forms more persistent

Resolution of CMA

1yr 56%, 2yr 77% 3yr 87% 5yr 92% 15yr 97%

Delayed reaction vs immediate

2yr 64%: 31% 3yr 92%: 53% 4yr 96%: 63%

A 99% reduction of IgE to CMP is associated with a 94% drop in CMP. Resolution occurs in most infants with IgE-CMA.

Persistency:

Infants reacting to <10 mL of milk

larger wheal size on SPT, are at increased risk for persistence.

J Pediatr. 2012 Apr 4.

Nutrient requirements for

breastfeeding women

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Micronutrient

Micronutrients affected by

maternal diet /

depletion7,8,9

Micronutrients unaffected

by maternal diet /

depletion7,8,9

Vitamin A Folate

Vitamin B1 Calcium

Vitamin B2 Iron

Vitamin B6 Copper

Vitamin B12 Zinc

Vitamin D

Selenium

Iodine

Benefits to

BABY

Benefits to

MOTHER

The Paediatric Centre

St LeonardsOUR SERVICES

Paediatric Allergy: Allergy testing and Immunotherapy

Neonatology

Allied Health

Clinical Psychologist, Occupational therapist; Physiotherapist, Speech

therapist, Dietician,

Any practical advice on your patient care please email or telephone:

info@thepaediatriccentre.com.au Tel: 94052386 Fax 94052387

www.thepaediatriccentre.com.au