Probiotic Administration in Early
Life, Atopy, and Asthma:
a Meta-analysis of Clinical Trial
Prof DR Dr Ariyanto Harsono S...
BACKGROUND AND OBJECTIVE:
Probiotics may reduce the risk of atopy
and asthma in children. However, results from
clinical t...
METHODS:
Random-effects models were used to calculate
pooled risk estimates. Meta-regression was
conducted to examine the ...
RESULTS:
Probiotics were effective in reducing total
immunoglobulin E (IgE) (mean reduction: –7.59 U/mL
[95% confidence in...
Administration of Lactobacillus acidophilus,
compared with other strains, was associated
with an increased risk of atopic ...
CONCLUSIONS:
Prenatal and/or early-life probiotic administration
reduces the risk of atopic sensitization and decreases
th...
Probiotics in infants for prevention of allergic
disease and food
hypersensitivity (Review)
Background:
Food hypersensitiv...
OBJECTIVES
To determine the effect of probiotics given to
high risk infants for the prevention of allergic
disease or food...
Outcome measures
Definitions of allergic disease and food
hypersensitivity had to be consistent with the
’Revised nomencla...
Primary outcomes:
• All allergic disease including asthma, eczema,
rhinitis or food allergy (analysis restricted to
studie...
Secondary outcomes (specific allergies and food
hypersensitivities):
• Asthma
• Dermatitis / eczema
• Allergic rhinitis
• ...
Methods of the Review
Eligibility of studies for inclusion was assessed independently
by each review author. The criteria ...
Effects are expressed as relative risk (RR), risk difference
(RD) and 95% confidence intervals (CI) for categorical
data, ...
Interventions
• L. acidophillus: allocated to infants to treatment
with Lactobacillus acidophilus versus placebo.
• L. joh...
 L. rhamnosus: Three studies allocated to infants to treatment with
Lactobacillus rhamnosus GG versus placebo.
 Probioti...
Allergy (outcome 01): One study (Kukkonen 2006) reported no significant difference
in all allergic disease in infants (RR ...
Food hypersensitivity (outcomes 02-3): No study reported food
hypersensitivity (all manifestations). Meta-analysis of 2 st...
Asthma (outcome 04): Meta-analysis of two studies found no significant
difference in asthma incidence in infancy and no
si...
Eczema (outcomes 05-6) finding:
Significant reduction in infant eczema (typical
RR 0.82, 95% CI 0.70, 0.95). However,
sig...
23
No significant difference in atopic eczema in
infants (typical RR 0.80, 95% CI 0.62, 1.02).
Again, significant (p = 0.04) ...
25
Allergic rhinitis (outcome 07): reported no significant difference in allergic
rhinitis in infants and no significant diff...
Food hypersensitivity and allergy (outcomes 08-10): reported no significant
difference in food allergy in infants, no sign...
28
29
Urticaria (outcome 11): reported no significant difference in urticaria in
infants.

30
DISCUSSION
The primary outcomes of this review were all manifestations of allergic
disease and food hypersensitivity with ...
One study assessed outcomes up to four years of
age and reported that difference in eczema
persisted, but there was no sig...
CONCLUSIONS

There is insufficient evidence to recommend the
addition of probiotics to infant feeds for
prevention of alle...
1. Elazab N, Mendy A, Gazana J, Vieira ER,
Quizon A, Forno E. Pediatrics 2013;132:e666–
e676
2. Osborn DA, Sinn JK. Probio...
Thank You
Prof Ariyanto Harsono MD PhD SpA(K)

36
Probiotic administration in early life, atopy, and asthma, a meta analysis of clical trial
Probiotic administration in early life, atopy, and asthma, a meta analysis of clical trial
Probiotic administration in early life, atopy, and asthma, a meta analysis of clical trial
Probiotic administration in early life, atopy, and asthma, a meta analysis of clical trial
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Probiotics, atopy, asthma, allergy prevention, meta analysis

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Probiotic administration in early life, atopy, and asthma, a meta analysis of clical trial

  1. 1. Probiotic Administration in Early Life, Atopy, and Asthma: a Meta-analysis of Clinical Trial Prof DR Dr Ariyanto Harsono SpA(K)
  2. 2. BACKGROUND AND OBJECTIVE: Probiotics may reduce the risk of atopy and asthma in children. However, results from clinical trials have been conflicting, and several of them may have been underpowered. We performed a meta-analysis of randomized, placebo-controlled trials to assess the effects of probiotic supplementation on atopic sensitization and asthma/wheeze prevention in children. Prof Ariyanto Harsono MD PhD SpA(K)
  3. 3. METHODS: Random-effects models were used to calculate pooled risk estimates. Meta-regression was conducted to examine the effect of potential factors on probiotics efficacy Prof Ariyanto Harsono MD PhD SpA(K)
  4. 4. RESULTS: Probiotics were effective in reducing total immunoglobulin E (IgE) (mean reduction: –7.59 U/mL [95% confidence interval (CI): –14.96 to –0.22]; P = .044). Meta-regression showed that the reduction in IgE was more pronounced with longer follow-up. Probiotics significantly reduced the risk of atopic sensitization when administered prenatally (relative risk: 0.88 [95% CI: 0.78 to 0.99]; P = .035 for positive result on the skin prick test and/or elevated specific IgE to common allergens)and postnatally (relative risk: 0.86 [95% CI: 0.75 to 0.98]; P = .027 for positive result on skin prick test). Prof Ariyanto Harsono MD PhD SpA(K)
  5. 5. Administration of Lactobacillus acidophilus, compared with other strains, was associated with an increased risk of atopic sensitization (P = .002). Probiotics did not significantly reduce asthma/wheeze (relative risk: 0.96 [95% CI: 0.85 to 1.07]).
  6. 6. CONCLUSIONS: Prenatal and/or early-life probiotic administration reduces the risk of atopic sensitization and decreases the total IgE level in children but may not reduce the risk of asthma/wheeze. Follow-up duration and strain significantly modified these effects. Elazab N, Mendy A, Gazana J, Vieira ER, Quizon A, Forno E. Pediatrics 2013;132:e666–e676
  7. 7. Probiotics in infants for prevention of allergic disease and food hypersensitivity (Review) Background: Food hypersensitivity and allergic disease are prevalent and represent a substantial health problem that may be increasing in developed countries. Genetic susceptibility plays a large role in the development of food allergy. Since breast feeding promotes the colonization of bifidobacteria and lactobacilli, subgroup analysis will examine the effect of probiotics in human milk fed infants separately to probiotics in formula fed infants.
  8. 8. OBJECTIVES To determine the effect of probiotics given to high risk infants for the prevention of allergic disease or food hypersensitivity. Prof Ariyanto Harsono MD PhD SpA(K) 11
  9. 9. Outcome measures Definitions of allergic disease and food hypersensitivity had to be consistent with the ’Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003’. Specific allergies were identified as atopic when confirmed by demonstration of an IgE response, either through skin testing or serological testing for specific IgE (e.g. RAST or EAST or CAP system). Prof Ariyanto Harsono MD PhD SpA(K) 12
  10. 10. Primary outcomes: • All allergic disease including asthma, eczema, rhinitis or food allergy (analysis restricted to studies reporting composite manifestations of all allergic disease); • Food hypersensitivity.
  11. 11. Secondary outcomes (specific allergies and food hypersensitivities): • Asthma • Dermatitis / eczema • Allergic rhinitis • Cow’s milk or soy protein hypersensitivity • Cow’s milk or soy protein allergy • Food allergy • Urticaria • Anaphylaxis Prof Ariyanto Harsono MD PhD SpA(K) 14
  12. 12. Methods of the Review Eligibility of studies for inclusion was assessed independently by each review author. The criteria and standard methods of the Cochrane Neonatal Review Group were used to assess the methodological quality of the included trials. Quality of the included trials were evaluated in terms of adequacy of randomization and allocation concealment, blinding of parents or careers and assessors to intervention, and completeness of assessment in all randomized individuals. Each review author extracted the data separately. Data were compared and differences resolved by consensus. The standard methods of the Neonatal Review Group were used to synthesize the data. Prof Ariyanto Harsono MD PhD SpA(K) 15
  13. 13. Effects are expressed as relative risk (RR), risk difference (RD) and 95% confidence intervals (CI) for categorical data, and weighted mean difference (WMD) and 95% CI for continuous data. Data was examined for heterogeneity using the chi-square test for heterogeneity. Heterogeneity was quantified using the I2 statistic. The fixed effect model was used for metaanalysis where enrolled infants and interventions are similar and no significant heterogeneity was found. Sources of heterogeneity were explored in subgroup analysis. Prof Ariyanto Harsono MD PhD SpA(K) 16
  14. 14. Interventions • L. acidophillus: allocated to infants to treatment with Lactobacillus acidophilus versus placebo. • L. johnsonii: allocated to infants to treatment with Lactobacillus johnsonii versus prebiotic (fructooligosaccharide) supplemented formula versus control formula. • L. reuteri: allocated to infants to treatment with Lactobacillus reuteri versus placebo given to the mother four weeks before delivery, then mother and baby daily for 12 months. Prof Ariyanto Harsono MD PhD SpA(K) 17
  15. 15.  L. rhamnosus: Three studies allocated to infants to treatment with Lactobacillus rhamnosus GG versus placebo.  Probiotic mixtures: allocated to infants to treatment with a mixture of Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus versus placebo mixed in infant feeds. Lin 2005 allocated infants to treatment with a mixture of Lactobacillus acidophilus and Bifidobacterium infantis versus control.  Mixtures of pro and prebiotics: allocated to infants to treatment with a probiotic and prebiotic mixture of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus, Bifidobacterium breve and Propionibacterium freudenreichii, and galacto-oligosaccharide 0.8g versus placebo (no probiotic or prebiotic).  Reported bacteria counts, doses, formulations and controls are documented in ’table of included studies’. Prof Ariyanto Harsono MD PhD SpA(K) 18
  16. 16. Allergy (outcome 01): One study (Kukkonen 2006) reported no significant difference in all allergic disease in infants (RR 0.90, 95% CI 0.75, 1.08). 19
  17. 17. Food hypersensitivity (outcomes 02-3): No study reported food hypersensitivity (all manifestations). Meta-analysis of 2 studies found no significant difference in food hypersensitivity manifest as gastrointestinal symptoms in infancy (typical RR 1.04, 95% CI 0.27, 4.03). 20
  18. 18. Asthma (outcome 04): Meta-analysis of two studies found no significant difference in asthma incidence in infancy and no significant difference in asthma prevalence in childhood. 21
  19. 19. Eczema (outcomes 05-6) finding: Significant reduction in infant eczema (typical RR 0.82, 95% CI 0.70, 0.95). However, significant (p = 0.03) and substantial heterogeneity was found. Significant reduction in childhood eczema prevalence (RR 0.57, 95% CI 0.33, 0.97). Prof Ariyanto Harsono MD PhD SpA(K) 22
  20. 20. 23
  21. 21. No significant difference in atopic eczema in infants (typical RR 0.80, 95% CI 0.62, 1.02). Again, significant (p = 0.04) and substantial heterogeneity was found. Prof Ariyanto Harsono MD PhD SpA(K) 24
  22. 22. 25
  23. 23. Allergic rhinitis (outcome 07): reported no significant difference in allergic rhinitis in infants and no significant difference in childhood prevalence of allergic rhinitis incidence. 26
  24. 24. Food hypersensitivity and allergy (outcomes 08-10): reported no significant difference in food allergy in infants, no significant difference in cow’s milk protein hypersensitivity in infants, no significant difference in childhood prevalence, no significant difference in cow’s milk protein allergy in infants. 27
  25. 25. 28
  26. 26. 29
  27. 27. Urticaria (outcome 11): reported no significant difference in urticaria in infants. 30
  28. 28. DISCUSSION The primary outcomes of this review were all manifestations of allergic disease and food hypersensitivity with one study reporting no significant difference in all allergic disease. No studies reported all manifestations of food hypersensitivity. For specific allergies in infants, no significant difference was found overall for gastrointestinal manifestations of food allergy, asthma, allergic rhinitis, food allergy (confirmed by skin prick test or specific IgE), cow’s milk protein hypersensitivity, cow’s milk protein allergy, and urticaria. Meta-analysis of five studies reporting the outcomes of 1477 infants found a significant reduction in infant eczema. However, there was significant and substantial heterogeneity between studies. When the analysis was restricted to studies reporting atopic eczema (confirmed by skin prick test or specific IgE) the findings were no longer significant. Prof Ariyanto Harsono MD PhD SpA(K) 32
  29. 29. One study assessed outcomes up to four years of age and reported that difference in eczema persisted, but there was no significant difference in asthma, allergic rhinitis or cow’s milk protein hypersensitivity. Although most studies had adequate randomization, allocation concealment, and blinded intervention, nearly all studies had substantial losses to follow up. No study was eligible for inclusion in the pre specified analysis of studies of adequate methodology. Prof Ariyanto Harsono MD PhD SpA(K) 33
  30. 30. CONCLUSIONS There is insufficient evidence to recommend the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity. Although there was a reduction in clinical eczema in infants, this effect was not consistent between studies and caution is advised in view of methodological concerns regarding included studies. Prof Ariyanto Harsono MD PhD SpA(K) 34
  31. 31. 1. Elazab N, Mendy A, Gazana J, Vieira ER, Quizon A, Forno E. Pediatrics 2013;132:e666– e676 2. Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity (Review). The Cochrane Collaboration 2008. http://www.thecochranelibrary.com, accessed 29, Oct 2013.
  32. 32. Thank You Prof Ariyanto Harsono MD PhD SpA(K) 36

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