Table 2: Detailed Characteristics of Included Studies.

Study ID Sample Size Age Range (months) Intervention Dose Duration (Days) Outcome(s) Findings
Probiotics
Baldassarre 2010 62 0-12 EHF + Lactobacillus GG
vs.
EHF alone
2.5 x 107 (CFU)/g 28 • Changes in fecal calprotectin levels
• Presence of occult blood in stool
• Fecal calprotectin decrease among EHF + LGG group was significantly larger than decrease among EHF - LGG group
• After 4 weeks, 0/12 patients in EHF + LGG group exhibited occult in blood stool, whereas 5/14 in the EHF - LGG group exhibited occult blood in stool
Hol 2008 119 0-6 EHF + Lactobacillus casei CRL431 and Bifidobacterium lactis Bb-12
vs.
EHF alone
107 (CFU)/g 365 • Development of clinical tolerance to cow's milk
• Analysis of T- and B-lymphocyte subsets
• Changes in SCORAD index
• Effects on wheezing and hospital admissions
• Tolerance development in probiotic group compared to placebo group after 6 months and 12 months was not significant.
• Treatment significantly decreased CD3+ and CD3+CD4+ levels in the probiotic group
• SCORAD index significantly improved in probiotic group at 6 months and 12 months, and significantly improved in placebo group at 6 months only. After adjusting for baseline values, there was no significant change from baseline between probiotic and placebo groups.
• Treatment had no effect on hospital admissions and wheezing.
Isolauri 2000 27 4.6 EHF + Bifidobacterium lactis Bb-12 or Lactobacillus GG
vs.
EHF alone
LGG: 3 x 108 (CFU)/g
Bifidobacterium lactis: 1 x 109 (CFU)/g
60 • Extent and severity of atopic eczema
• Serum concentrations of soluble cell surface molecules, cytokines/chemokines, and urine concentrations of methyl-histamine and eosinophilic protein
• After 2 months, there was a significant decrease in SCORAD index for both probiotic groups
• After 6 months, the SCORAD index had decreased to 0 in all groups
• After 2 months, serum CD4 concentration decreased in both probiotic groups, but not the unsupplemented group
• Serum TGF-β1 concentrations decreased in those receiving Bifidobacterium lactis Bb-12, but increased in those receiving Lactobacillus GG
• Serum concentrations of IL-1ra, TNFα, GM-CSF, sICAM-1, RANTES and MCP-1α were unaffected by probiotics
Kirjavainen 2003 35 3.5-6.8 EHF + viable Lactobacillus GG or heat-inactivated Lactobacillus GG
vs.
EHF alone
1 x 109 (CFU/g) 52.5 • Changes in SCORAD index
• Changes in microbial cell counts in feces
• Adverse gastrointestinal effects were noted among the heat-inactivated LGG group and this intervention was discontinued
• Mean decrease in SCORAD index was greater in the viable LGG group than in the placebo group
• Treatment groups did not show a significant change in bacterial numbers in fecal samples
Majamaa 1997 31 2.5-15.7 EHF + Lactobacillus GG
vs.
EHF alone
5 x 108 (CFU)/g 60 • Changes in severity of atopic eczema
• Changes in intestinal inflammation via concentrations of fecal α1-antitrypsin, eosinophil cationic protein (ECP), and tumor necrosis factor-α (TNF-α)
• Changes in systemic immune response via concentrations of ECP and cytokine production of peripheral blood mononuclear cells
• The clinical score of atopic dermatitis (SCORAD) significantly improved within the EHF + LGG group only
• Concentrations of fecal α1-antitrypsin and TNF-α significantly decreased among EHF + LGG group only
• Fecal ECP concentrations were not affected by treatment
Prebiotics
Boženský 2015 120 1.5-2 EHF + galacto-oligosaccharides
vs.
EHF alone
0.5g / 100ml 182.5 • Severity of atopic eczema as measured by SCORAD index
• Changes in anthropometric factors, tolerance, and incidence of infection
• While both groups showed a decrease in SCORAD index, there was no significant difference in reduction between the two groups
• There was no significant difference in anthropometry, tolerance, or incidence of infection among the two groups
Synbiotics
Burks 2015 110 0-8 AAF + oligofructose, long-chain inulin, acidic oligosaccharides, Bifidobacterium breve M-16V
vs.
AAF alone
Prebiotic blend: 8 g/l (6.8 g/l oligofructose:inulin 9:1 and 1.2 g/l pAOS)
Bifidobacterium breve M-16V: 1.47 x 109 (CFU)/100 ml
112 • Changes in growth (weight, length, head circumference)
• Allergic symptoms consisting of dermatological (SCORAD index), respiratory, and gastrointestinal
• Changes in consistency, frequency, and color of stool
• Changes in formula intake
• Changes in fecal pH and fecal short-chain fatty acids
• An increase in weight, length, and head circumference was seen in both groups, but there was no significant difference between the groups
• 22% of subjects in the treatment group reported diarrhea, whereas 4% in the control group reported diarrhea
• 2% of subjects in the treatment group were treated for infection, whereas 18% in the control group were treated for infection
• SCORAD index and severity of other allergy symptoms decreased for both groups but there was no significant decrease between the groups
• Flatulence, stool frequency, and stool consistency was not significantly different between both groups
• Stool color showed significant improvement in the treatment group
• Fecal pH was significantly lower among the treatment group
• For the treatment group, acetic acid levels were significantly higher while propionic acid levels were lower
Burks 2014 110 0-8 AAF + oligofructose, long-chain inulin, acidic oligosaccharides, Bifidobacterium breve M-16V
vs.
AAF alone
Prebiotic blend: 8 g/l (6.8 g/l oligofructose:inulin 9:1 and 1.2 g/l pAOS)
Bifidobacterium breve M-16V: 1.47 x 109 (CFU)/100 ml
112 • Changes in growth (weight, length, head circumference)
• Formula tolerance
• Changes in SCORAD index
• Evidence of respiratory allergic symptoms
• Stool consistency, frequency, and color
• Incidence of adverse events and medication use
• Both formulas supported normal growth, there was no significant difference in growth between the two groups
• Both formulas were equally tolerated and reduced allergic symptoms with no significant differences between the two groups
• SCORAD index decreased in both groups with no significant differences between the two groups
• The treatment group reported softer and yellow/brown stools, whereas the control group reported dry and green/dark brown stools
• Incidence of infection and antibiotic use was lower in the treatment group
Harvey 2014 30 0-36 AAF + Bifidobacterium breve M16-V and neutral fructo-oligosaccharides mixture
vs.
AAF alone
Prebiotic Mixture: 0.8 g/100 ml
Bifidobacterium breve M16-V: 1.47 x 109 CFU/100ml
7 •Acceptance of formula
• Hypoallergenicity (absence of clinical symptoms)
• Incidence of adverse events
• No serious adverse events were reported upon synbiotic addition
• Demonstrated at 95% confidence that at least 90% of infants would have no reaction to synbiotic addition, therefore establishing the formula as hypoallergenic
Van Der Aa 2010 90 0-7 EHF + Bifidobacterium breve M16-V and short chain galacto-/long chain fructooligosaccharide mixture
vs.
EHF alone
Prebiotic Mixture: 0.8 g/100 ml
Bifidobacterium breve M-16-V: 1.3 x 109 CFU/100ml
84 • Severity of atopic dermatitis measured by SCORAD index
• Changes in total and specific IgE and eosinophilic granulocytes
• SCORAD index decreased for both groups, but there was no significant difference in SCORAD index between the groups at any time
• Total and specific serum IgE and eosinophilic granulocytes were unaffected by treatment
• In a subgroup of infants with elevated total or specific IgE, there was a significantly greater improvement in SCORAD index in the treatment group than in the control group
Van Der Aa 2009 90 0-7 EHF + Bifidobacterium breve M16-V and short chain galacto-/long chain fructooligosaccharide mixture
vs.
EHF
Prebiotic Mixture: 0.8 g/100 ml
Bifidobacterium breve M-16V: 1.3 x 109 CFU/100ml
84 • Bacterial composition, pH, lactate, and short-chain fatty acids in fecal samples
• Changes in fecal consistency and frequency
• The treatment group demonstrated a significantly higher detection rate of B. breve M16-V and concentrations of D-lactate and L-lactate than controls.
• The treatment group had a significantly lower fecal pH than controls
• The treatment group demonstrated higher proportions of acetic acid and lower proportions of butyric when compared to controls
• Fecal consistency was reported to be significantly softer and constipation was reported less often in the treatment group

Abbreviations:
EHF: Extensively hydrolyzed protein formula
AAF: Amino acid-based formula