25-Feb-16

1

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

Health Nut Study 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

Eczema InfancyComparison Number of subjects (studies) RR (95% CI)

Maternal allergen avoidance

during pregnancy

334(2) 1.01 (0.51, 1.79)

Maternal allergen avoidance

during lactation

26(1) 0.73 (0.32, 1.64)

Partially hydrolysed formula

versus cow’s milk formula

1745 (8) 0.99(0.84, 1.01)

Extensively hydrolysed

formula versus cow’s milk

formula

1726 (3) 0.71 (0.51, 0.97)

Extensively versus partially

hydrolysed formula

1865 (4) 0.89 (0.73, 1.10)

Soy formula versus cow’s

milk formula

451 (1) 1.20 (0.95, 1.52)

Prebiotics 1218 (4) 0.68 (0.48, 0.97)

Probiotics 1911 (13) 0.79 (0.68, 0.91)

25-Feb-16

2

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

Eczema – Probiotic containing

L. rhamnosus versus other probiotic

Test for subgroup differences: P = 0.18, I² = 45.3%

RR 0.68 95%CI 0.53, 0.86

RR 0.83 95%CI 0.70, 1.00

Early Pregnancy and probiotics

Laitinen 2008: RCT New Zealand Study 256 women: 7% obese, 21% overweight Placebo/diet vs LACTOBACILLUS

RHAMNOSUS GG AND BIFIDOBACTERIUM LACTIS

Lactobacillus acidophilus: Group preserve insulin sensitivity Improve Glycaemic control

Obese and GDM: have decrease microbial diversity

Probiotics for preventions of GDM

2014 Cochrane: Barrett HL et al

Maternal Probiotics and Genital

infection

25-Feb-16

3

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

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

Suggestions from a MidwifeDecrease use of antibiotics

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

25-Feb-16

4

Top Food Prebiotics: 8g per dayChicory: 64% fiber by weight ingest 10g

Jerusalem Antichokes 31% 19g

Dandelion Greens: 24% 25g

Garlic 17% 34g

Leek 11% 51g

Onion: 8% 70g

Asparagus: 5% 120g

Bran: 5% 120g

Wheat flour: 5% 120g

Banana: 1% 600g

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 third largest component of Human

Milk 20 - 23 gm/l in colostrum & 12- 14 gm/ in mature milk.

Polydextrose – Fructans

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

FOS (Fructo-oligosaccharides or oligofructose) plants.

GOS (Galacto-oligosaccharides) milk. (also known as TOS – trans-galacto-oligosaccharides)

Lactulose - Lactosucrose

SOS (soy-oligosaccharides);XOS (xylo-oligosaccharides)

IMO (isomalto-oligosaccharides) corn & wheat.

Lactitol(Journal of the American Dietetic

Assosciatio,2008)

Short chain fatty acids (SCFAs) are the products of colonic bacterial degradation of unabsorbed starch and non-starch polysaccharide (fibre).

The main acids: Acetate, Propionate, and Butyrate and Lactic acid.

They are important anions in the

colonic lumen, affecting both

Colonocyte Morphology

(Proliferation / Differentiation)

& Function (Tight Colonic Junction

/ Inflammatory Suppression).

POSTbiotics

• SCFA facilitate absorption of water and electrolytes

• minimizing the risk of diarrhea as well as its volume.

• Acetate increases colonic blood flow and enhances ileal motility.

• SCFA may be involved in the:

Ileo - Colonic Brake”Stimulates contractions of the

ileum and shortens ileal

emptying.

SCFA help improve Water & Electrolyte Absorption

25-Feb-16

5

Butyrate is the preferred energysubstrate for the colonocyte, itprovides fuel (nutrition) for ileal andcolonic epithelial cells, which helpmaintain the integrity of the colon.

LOW Resistant Starch & Fiber Diet low SCFA production in colon explain the high occurrence of colonic disorders.

SCFA support the critical

Gut mucosal barrier: Keeping Gut integrity

Prebiotic 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%

Subgroup analysis: Infant risk of allergy

Infant asthma incidence

Test subgroup differences: P = 0.07, I² = 69%

RR 0.37 95%CI 0.14, 0.96

RR 1.07 95%CI 0.56, 2.06

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

GIT transitional TimeStool consistency

Preterm infants

25-Feb-16

6

Antibiotic-associated Diarrhea

Systematic review: 9 RCT (2 in children):

60% reduction in incidence and duration of antibiotic associated 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

Probiotics: constipation

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

2 children,

n = 111

In children, L. casei rhamnosus Lcr35, but not L.

rhamnosus GG, showed a beneficial effect.

Chmielewska A. World J Gastroenterol, 2010

Probiotics: Respiratory Illness

Weizman, et al. 12 weeks of B lactis or L reuteri

Significant reductions, all favoring L reuteri in

Days with fever (0.17 vs. 0.8, P<0.001)

Episodes of fever (0.1 vs. 0.4, P<0.001)

Antibiotic prescriptions (0.06 vs. 0.19, P<0.05)

Weizman, Pediatrics, 2005

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

Diarrhoea

Probiotics/ prebiotics,

Electrolyte

Lactose Intolerance. Reducing substance > 2% required

LF formula or Soy

25-Feb-16

7

Colic and irritable baby

HA: increase transit time

Probiotic: L reuteri

prebiotic formula

Cow milk intolerance

Proton pump inhibitor or H2 receptor antagonist:

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

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

Hydrolysed formula and colic

Systematic review

Partial or extensive hydroylysed

formula reduce colic but not soy

No role of soy in the prevention or management of infantile colic or regurgitation

Reflux

AR formula Casein dominantIncrease constipation

Whey 100% less constipationThickener to breast milkNot use antacid as high

Aluminium content

25-Feb-16

8

Any Allergy

Hydrolysed Formula vs CM: 2013

Eczema

Hydrolysed formula vs CMF 2013 Cochrane

RR 0.99, 95%CI 0.84, 1.17

RR 0.92, 95%CI 0.70, 1.20

Soy vs Cow’s milk: Eczema

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

Vit D supplements does not increase in infant Vit D levels

unless 3000IU per day.

25-Feb-16

9

Folic acid

Before conception

No evidence after first trimester is beneficial

Increase methylation and increase allergy

0.4mg per day

But if Obese, on anticonvulsants, NIDDM and

FHx of NTD for 5mg daily

Lin 2013 JACI

Low asthma rate if low folate level

Is there an “Optimal Window” for introducing solids?

Birth >12 months

resolutionwindowrisk risk

? ?

Tolerance

induction

3-4 6-7

Currently speculative: Based on preliminary evidence that

complementary feeding in 4-6mo window reduces risk of:• Food allergy Poole et al. 2006

• Coeliac autoimmunity Norris et al. 2005

• Islet cell autoimmunity Norris et al. 2003

Importance oral exposure

Eg topical creams with any food oils and proteins

Nutrient requirements for

breastfeeding womenDietary Guidelines

Serves per day

19 – 50 years

Vegetables Fruit Grains Lean Meats Dairy

Women 5 2 6 2.5 2.5

Pregnant 5 2 8.5 3.5 2.5

Breastfeeding 7.5 2 9 2.5 2.5

How much is a serve?

½

cup 1 cup

½

cup

2/3

cup1 slice

25-Feb-16

10

Adherance to Guidelines

National Survey of pregnant

women in Australia (n=857)

Objective: assess dietary intake

of pregnant women against the

Australian Dietary Guidelines

with respect to the 5 food group

Key results: Almost 2/3 of women

rated diet as healthy during

pregnancy however, none met the

recommendations for all five

food groups

37% of women did not meet any

of the recommendations

Group I and Group II vitamins

inadequacies may decrease want to breast feed

Group I: increase with supplementation

thiamin, riboflavin, Vit B6, B12, A, D, choline, retinol,

selenium, and iodine

Group II:

folate, calcium, iron, copper, and zinc

Unaffected by maternal intake or status

Supplementation helps mother not infant.

Supplementation during lactation

Depend on demographic and culture

White take more than black

Higher socio economic more supplementation

Mothers who take supplements more likely to continue breast feeding

Require:

1/3 increase in protein

LCPUFA and Vit A, C, D, E and Fe ,Zn

Ca, Po4 is the same as non pregnant

Mastitis

Dysbiosis

Single strain of pathogenic bacteria

Lactobacillus disappear

Most common organism is Staph Aureus, Staph Epi esp

chronic infection

L Fermentum

L Salivarius

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

:

25-Feb-16

11

Bacterial Count Lactobacillus vs Antibiotics

Results 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

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

25-Feb-16

12

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

A second factor that may play a role in

long-term outcomes is:

High protein intake in infancy

Rapid weight gain in infancy

High energy intake

Catch up growth

IUGR

postnatal catch up growth

increase central fat

Systematic review of 24 studies

Main outcome measure was obesity at any age after infancy

Infants who grow more rapidly are at increased risk of obesity

OR = 1.35 to 9.38 times

Associations were consistent for obesity at different ages and for people born over a period from 1927 to 1994

Baird 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.

Weight Gain

Too fast Weight Gain in infancy is associated with

obesity

For every 1sd change in weight for length gain during

the first yr

OR 1.87 (1.10-3.18) chance of obesity at 14-16yr

Monteiro

A third factor that may play a role in

long-term outcomes is:

High protein intake in infancy

Rapid weight gain in infancy

High energy intake

In infancy may be associated with weight gain in later childhood

25-Feb-16

13

Ong KK, et al. Dietary energy intake at the age of 4 months predicts postnatal weight gain and childhood body mass index. Pediatrics. 2006 Mar;117(3):e503-8.

As energy intake increased, proportion of infants

with rapid weight gain (shaded columns) increased

Energy intake also linked to later

weight gain

Percentage of infants showing rapid growth based on energy

intake at 4 months

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

Hydrolysed formula

Vit D

The Paediatric Centre

St LeonardsOUR SERVICES

Paediatric Allergy: Allergy testing and Immunotherapy

Neonatology

Developmental Paediatrician: Dr Susie Gardner

Paediatric Nephrologist: Dr Fiona Mackie

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