Probiotics in infants for prevention of allergic disease and food hypersensitivity

David A Osborn; John KH Sinn

doi:10.1002/14651858.CD006475.pub2

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Analysis 1.1

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 1 All allergic disease.

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Analysis 1.3

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 3 Food hypersensitivity (gastrointestinal symptoms).

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Analysis 1.4

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 4 Asthma.

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Analysis 1.5

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 5 Eczema.

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Analysis 1.6

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 6 Atopic eczema.

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Analysis 1.7

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 7 Allergic rhinitis.

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Analysis 1.8

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 8 Food allergy.

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Analysis 1.9

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 9 Cow's milk protein hypersensitivity.

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Analysis 1.10

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 10 Cow's milk protein allergy.

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Analysis 1.11

Comparison 1 Probiotic versus no probiotic ‐ all infants, Outcome 11 Urticaria.

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Analysis 2.1

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 1 All allergic disease.

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Analysis 2.2

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 2 Food hypersensitivity (gastrointestinal symptoms).

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Analysis 2.3

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 3 Asthma.

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Analysis 2.4

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 4 Eczema.

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Analysis 2.5

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 5 Atopic eczema.

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Analysis 2.6

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 6 Allergic rhinitis.

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Analysis 2.7

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 7 Food allergy.

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Analysis 2.8

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 8 Cow's milk protein hypersensitivity.

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Analysis 2.9

Comparison 2 Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity, Outcome 9 Urticaria.

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Analysis 3.1

Comparison 3 Probiotic versus no probiotic in infants not selected for risk of allergy or food hypersensitivity, Outcome 1 Atopic eczema.

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Analysis 3.2

Comparison 3 Probiotic versus no probiotic in infants not selected for risk of allergy or food hypersensitivity, Outcome 2 Cow's milk protein hypersensitivity.

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Analysis 3.3

Comparison 3 Probiotic versus no probiotic in infants not selected for risk of allergy or food hypersensitivity, Outcome 3 Cow's milk protein allergy.

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Analysis 4.1

Comparison 4 Probiotic versus no probiotic in infants fed exclusive human milk, Outcome 1 Food hypersensitivity (gastrointestinal symptoms).

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Analysis 4.2

Comparison 4 Probiotic versus no probiotic in infants fed exclusive human milk, Outcome 2 Eczema.

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Analysis 4.3

Comparison 4 Probiotic versus no probiotic in infants fed exclusive human milk, Outcome 3 Cow's milk protein hypersensitivity.

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Analysis 5.1

Comparison 5 Probiotic versus no probiotic in infants fed cow's milk formula, Outcome 1 Atopic eczema.

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Analysis 5.2

Comparison 5 Probiotic versus no probiotic in infants fed cow's milk formula, Outcome 2 Cow's milk protein hypersensitivity.

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Analysis 5.3

Comparison 5 Probiotic versus no probiotic in infants fed cow's milk formula, Outcome 3 Cow's milk protein allergy.

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Analysis 6.1

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 1 Food hypersensitivity (gastrointestinal symptoms).

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Analysis 6.2

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 2 Asthma.

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Analysis 6.3

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 3 Eczema.

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Analysis 6.4

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 4 Atopic eczema.

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Analysis 6.5

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 5 Allergic rhinitis.

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Analysis 6.6

Comparison 6 Probiotic versus no probiotic in infants fed a hydrolysed formula, Outcome 6 Urticaria.

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Analysis 7.1

Comparison 7 Probiotic with added prebiotic versus no probiotic, Outcome 1 All allergic disease.

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Analysis 7.2

Comparison 7 Probiotic with added prebiotic versus no probiotic, Outcome 2 Eczema.

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Analysis 7.3

Comparison 7 Probiotic with added prebiotic versus no probiotic, Outcome 3 Atopic eczema.

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Analysis 8.1

Comparison 8 Specific probiotic versus no probiotic, Outcome 1 All allergic disease.

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Analysis 8.2

Comparison 8 Specific probiotic versus no probiotic, Outcome 2 Food hypersensitivity (gastrointestinal symptoms).

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Analysis 8.3

Comparison 8 Specific probiotic versus no probiotic, Outcome 3 Asthma.

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Analysis 8.4

Comparison 8 Specific probiotic versus no probiotic, Outcome 4 Eczema.

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Analysis 8.5

Comparison 8 Specific probiotic versus no probiotic, Outcome 5 Atopic eczema.

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Analysis 8.6

Comparison 8 Specific probiotic versus no probiotic, Outcome 6 Allergic rhinitis.

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Analysis 8.7

Comparison 8 Specific probiotic versus no probiotic, Outcome 7 Food allergy.

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Analysis 8.8

Comparison 8 Specific probiotic versus no probiotic, Outcome 8 Cow's milk protein hypersensitivity.

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Analysis 8.9

Comparison 8 Specific probiotic versus no probiotic, Outcome 9 Cow's milk protein allergy.

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Analysis 8.10

Comparison 8 Specific probiotic versus no probiotic, Outcome 10 Urticaria.

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Comparison 1. Probiotic versus no probiotic ‐ all infants

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All allergic disease Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.75, 1.08]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Food hypersensitivity	0		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.1 Infant incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Food hypersensitivity (gastrointestinal symptoms) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	2	247	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.27, 4.03]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Asthma Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Infant incidence	2	363	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.38, 1.80]
4.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [0.33, 28.46]
5 Eczema Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Infant incidence	5	1477	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.70, 0.95]
5.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.33, 0.97]
6 Atopic eczema Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 Infant incidence	4	1356	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.62, 1.02]
6.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Allergic rhinitis Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.03, 2.15]
7.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	2.04 [0.75, 5.56]
8 Food allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Infant incidence	1	175	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.70, 3.37]
8.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Cow's milk protein hypersensitivity Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Infant incidence	3	239	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [0.75, 2.96]
9.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.15, 6.97]
10 Cow's milk protein allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.02, 9.84]
10.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Urticaria Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	2.94 [0.31, 27.73]
11.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Probiotic versus no probiotic ‐ all infants

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Comparison 2. Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All allergic disease Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.75, 1.08]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Food hypersensitivity (gastrointestinal symptoms) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	2	247	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.27, 4.03]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Asthma Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	2	363	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.38, 1.80]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [0.33, 28.46]
4 Eczema Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Infant incidence	5	1477	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.70, 0.95]
4.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.33, 0.97]
5 Atopic eczema Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Infant incidence	3	1284	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.63, 1.04]
5.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Allergic rhinitis Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.03, 2.15]
6.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	2.04 [0.75, 5.56]
7 Food allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Infant incidence	1	175	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.70, 3.37]
7.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Cow's milk protein hypersensitivity Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Infant incidence	2	167	Risk Ratio (M‐H, Fixed, 95% CI)	1.96 [0.93, 4.14]
8.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.3 Childhood prevalence	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.15, 6.97]
9 Urticaria Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	2.94 [0.31, 27.73]
9.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Probiotic versus no probiotic in infants at high risk of allergy or food hypersensitivity

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Comparison 3. Probiotic versus no probiotic in infants not selected for risk of allergy or food hypersensitivity

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Atopic eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.21, 1.89]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Cow's milk protein hypersensitivity Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 3.32]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Cow's milk protein allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.02, 9.84]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. Probiotic versus no probiotic in infants not selected for risk of allergy or food hypersensitivity

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Comparison 4. Probiotic versus no probiotic in infants fed exclusive human milk

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Food hypersensitivity (gastrointestinal symptoms) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.17, 7.34]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	1	57	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.12, 0.85]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Cow's milk protein hypersensitivity Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	2.14 [0.59, 7.77]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 4. Probiotic versus no probiotic in infants fed exclusive human milk

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Comparison 5. Probiotic versus no probiotic in infants fed cow's milk formula

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Atopic eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.21, 1.89]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Cow's milk protein hypersensitivity Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 3.32]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Cow's milk protein allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.02, 9.84]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 5. Probiotic versus no probiotic in infants fed cow's milk formula

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Comparison 6. Probiotic versus no probiotic in infants fed a hydrolysed formula

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Food hypersensitivity (gastrointestinal symptoms) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.14, 6.81]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Asthma Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.27, 1.72]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.70, 1.53]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Atopic eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.32, 1.14]
4.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Allergic rhinitis Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.03, 2.15]
5.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Urticaria Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 Infant incidence	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	2.94 [0.31, 27.73]
6.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 6. Probiotic versus no probiotic in infants fed a hydrolysed formula

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Comparison 7. Probiotic with added prebiotic versus no probiotic

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All allergic disease Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Infant incidence	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.75, 1.08]
1.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Infant incidence	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.66, 0.99]
2.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Atopic eczema Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Infant incidence	1	922	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.51, 0.96]
3.2 Childhood incidence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Childhood prevalence	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 7. Probiotic with added prebiotic versus no probiotic

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Comparison 8. Specific probiotic versus no probiotic

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All allergic disease Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 L. rhamnosus, B. Breve and P. freudenreichii (with GOS) (infant incidence)	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.75, 1.08]
2 Food hypersensitivity (gastrointestinal symptoms) Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 L. reuteri (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.14, 6.81]
2.2 L. rhamnosus strain GG (infant incidence)	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.17, 7.34]
3 Asthma Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 L. reuteri (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.27, 1.72]
3.2 L. acidophilus (infant incidence)	1	175	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.30, 5.72]
3.3 L. rhamnosus strain GG (childhood prevalence)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [0.33, 28.46]
4 Eczema Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 L. reuteri (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.70, 1.53]
4.2 L. rhamnosus strain GG (infant incidence)	2	189	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.29, 0.72]
4.3 L. rhamnosus, B. Breve and P. freudenreichii (with GOS) (infant incidence)	1	925	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.66, 0.99]
4.4 L. acidophilus (infant incidence)	1	175	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.77, 1.58]
4.5 L. rhamnosus strain GG (childhood prevalence)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.33, 0.97]
5 Atopic eczema Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 L. reuteri (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.32, 1.14]
5.2 L. rhamnosus strain GG (infant incidence)	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.21, 1.89]
5.3 L. rhamnosus, B. Breve and P. freudenreichii (with GOS) (infant incidence)	1	922	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.51, 0.96]
5.4 L. acidophilus (infant incidence)	1	174	Risk Ratio (M‐H, Fixed, 95% CI)	1.87 [1.00, 3.52]
6 Allergic rhinitis Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 L. reuteri (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.03, 2.15]
6.2 L. rhamnosus strain GG (childhood prevalence)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	2.04 [0.75, 5.56]
7 Food allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 L. acidophilus (infant incidence)	1	175	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.70, 3.37]
8 Cow's milk protein hypersensitivity Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 L. rhamnosus strain GG (infant incidence)	3	239	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [0.75, 2.96]
8.2 L. rhamnosus strain GG (childhood prevalence)	1	107	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.15, 6.97]
9 Cow's milk protein allergy Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 L. rhamnosus strain GG (infant incidence)	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.02, 9.84]
10 Urticaria Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 L. rhamnosus strain GG (infant incidence)	1	188	Risk Ratio (M‐H, Fixed, 95% CI)	2.94 [0.31, 27.73]

Comparison 8. Specific probiotic versus no probiotic

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