Table 3.
Prebiotic supplementation of infant formula trials with allergic disease outcomes.
| Study design | Ref. | Outcomes | Population | Intervention | Control | Primary outcome |
|---|---|---|---|---|---|---|
| Randomized, controlled, double-blind trial with a 6- month intervention period from birth to 6 months of age. | [103] | AD at 6 months. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 102 EHF formula with added GOS: FOS (0.8 g/100 mL). | n = 104 EHF formula with added maltodextrine (0.8 g/100 mL) as placebo. | - At 6 months of age: fewer infants had AD in GOS: FOS group (9.8%) than the control group (23.1%; p = 0.014). |
| [97] | Follow-up until 2 years of age. AD, recurrent wheezing, number of infectious episodes and allergic urticaria at 2 years of age. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 66 hypoallergenic EHF with added GOS: FOS (0.8 g/100 mL). | n = 68 hypoallergenic EHF with added maltodextrine (0.8 g/100 mL) as placebo. | - The cumulative incidences of AD, recurrent wheezing, and allergic urticaria were lower in the GOS/FOS group (13.6, 7.6, 1.5%, respectively) than in the placebo group (27.9, 20.6, and 10.3%, respectively; p < 0.05). The number of overall infections and the number of fever episodes was lower in the GOS/FOS group than in the placebo group (p = 0.01 and p < 0.0001 respectively). | |
| [102] | Follow-up until 5 years of age. Cumulative incidence of allergic manifestations (AD, recurrent wheezing, allergic rhinoconjunctivitis and urticaria) during 5 years, and the prevalence of allergic and persistent allergic manifestations at 5 years. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 42 hypoallergenic EHF with added GOS: FOS (0.8 g/100 Ll). | n = 50 hypoallergenic EHF with added maltodextrine (0.8 g/100 mL) as placebo. | The 5 years cumulative incidences of any allergic manifestation and DA were significantly lower in the GOS/FOS group (30.9, 19.1 %, respectively) compared to placebo group (66, 38 %, respectively) (p < 0.01 and < 0.05). Children in the GOS/FOS group tended to have a lower incidence of allergic rhinoconjunctivitis, and allergic urticaria (4.8 vs 16% for both manifestations, p = 0.08). There was no difference in the cumulative incidence of recurrent wheezing. With regard to the prevalences at 5 years, intervention group had significantly lower prevalence of any persistent allergic manifestation and rhinoconjunctivitis (4.8, 2.4 %, respectively) compared to placebo (26, 14 %, respectively) (p < 0.01 and = 0.05). Prevalence of persistent AD tended to be lower in the intervention group (2.4 vs 12%, p = 0.09). Although intervention group had 75% reduction in the prevalence of persistent wheezing (4.8 vs 14 %), no significance was shown. | |
| [104] | Levels of total immunoglobulins and of cow’s milk protein at 6 months of age. | Term infants at risk of atopy due to parental history of allergic disease. | n = 41 hypoallergenic EHF with added GOS: FOS (0.8 g/100 mL). | n = 43 hypoallergenic EHF with added maltodextrine (0.8 g/100 mL) as placebo. | Total IgE, IgG1, IgG2 and IgG3 levels were significantly declined after GOS/FOS supplementation, whereas no significant differences in the levels of total IgG4 were observed between the two treatment groups. Ig levels were similar between infants with our without AD. Cow’s milk proteins-specific IgE levels were very low in all infants but cow’s milk proteins-specific-IgG1 was significantly decreased in the GOS/FOS-supplemented infants (p < 0.005). | |
| Randomized, controlled, double-blind trial with a 12- month intervention period from birth to 12 months of age. | [98] | AD at 12 months of age. | Term infants at low atopy risk due to no family history of allergic diseases. | n = 414 CM formula with added GOS: FOS (0.8 g/100 mL) and pAOS (0.12 g/100 mL). | n = 416 CM formula. | At 12 months of age, fewer infants had AD in GOS: FOS: pAOS group (5.7%) than the control group (9.7%; p = 0.04) and AD was less severe among the infants affected in the supplemented group (n = 8; median SCORAD score, 8; range, 3–25) than in the control group (n = 16; median SCORAD score, 12; range, 2–59; p = 0.08). |
| Randomized, controlled, double-blind trial with a 2- month intervention period from birth to 2 months of age. | [99] | Incidences of AD, obstructive bronchitis, recurrent wheezing, gastrointestinal and upper respiratory tract infections at 18 months of age. Gut microbiota composition at 2 months of age. | Term infants at low atopy risk due to no family history of allergic diseases. | n = 80 standard formula with added GOS: FOS (0.8 g/100 mL). | n = 80 standard formula | In infants fed with formula supplemented with GOS/FOS, fecal concentrations of Bifidobacteria and lactobacilli were significantly higher than infants fed with the standard formula (8.92 ± 1.011 and 7.22 ± 0.74 CFU/g for supplemented children respectively vs 7.81 ± 0.83 and 6.81 ± 0.93 CFU/g for non-supplemented children respectively p < 0.05). Infants fed with supplemented formula had significantly less allergic reactions to food products compared to the control infants (4.84% vs. 16.98%, p < 0,05).The incidence of AD was also the highest in control group (16.98% vs. 4.84% accordingly; p < 0.05). |
| Randomized, controlled, double-blind trial with a 6- month intervention period from birth to 6 months of age. | [101] | AD at 12 months of age. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 375 PHF formula with added GOS:FOS:pAOS (0.8 g/100 mL). | n = 383 CM formula. | At 12 months of age: There was no difference in the incidence of AD between the PHF GOS: FOS: pAOS intervention group (28.7%) and the CM formula control group (28.7%; p = 0.90). |
| Randomized, controlled, double-blind trial with a 26- month intervention period from birth to 26 months of age. | [106] | Fecal pH, bacterial taxonomic compositions and microbial metabolite levels in the first 26 weeks of life. To identify microbial patterns associated with the onset of eczema. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 51 PHF formula with added GOS: FOS (0.68 g/100 mL) and pAOS (0.12 g/100 mL). | n = 57 standard formula | Fecal microbial composition, metabolites, and pH of infants supplemented with FOS/GOS were closer to that of breast-fed infants than that of infants receiving standard formula. Infants with eczema by 18 months showed discordant development of bacterial genera of Enterobacteriaceae and Parabacteroides species in the first 26 weeks, as well as decreased acquisition of Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. |
| Randomized, controlled, double-blind trial with a 48 weeks intervention period from birth to 48 weeks of age. | [107] | AD outcomes at 36 weeks and 48 weeks of life. Common infections outcomes at 48 and 96 weeks of life. Relationship among early nutrition, gut microbiota and clinical outcomes. | Term infants at risk of atopy due to parental history of allergic diseases. | n = 201 EHF formula with added GOS: PDX (0.4 g/100 mL). | n = 199 standard formula | The cumulative number of infants with at least one episode of AD was not statistically different between infants supplemented or not with GOS/PDX at 36 weeks, 48 weeks and 96 weeks. The number of RIs episodes until 48 weeks were lower in infants supplemented with GOS/PDX than in infants fed with standard formula (p = 0.023) but no longer detected at 96 weeks. Bifidobacteria and Clostridium cluster I colonization increased over time in the supplemented group but decreased in the control groups. |
(AD : atopic dermatitis ; EHF : extensively hydrolysed formulas ; CM : cow’s milk ; SCORAD: Scoring atopic dermatitis, PHF: partially hydrolysed formulas, pAOS: pectin hydrolysate-derived acidic oligosaccharides; PDX: polydextrose).