A Double-Blind randomized placebo controlled clinical trial on the supplementation of Probiotics in the First six months of Life in Asian Infants at risk of allergic diseases - Effects on Development of Allergic Disease and Safety aspects with two year follow-up

Abstract

Background: The role of probiotics in allergy prevention remains uncertain but has been shown to have a possible protective effect on allergic diseases. Probiotics can modulate local and systemic immune responses, resulting in decrease in infectious disease and increase efficacy to vaccination.

Objectives: To assess the effect of probiotic supplementation in the first 6 months of life on i. allergic diseases at two years of age in Asian infants at risk of allergic disease. ii. specific antibody response against Hepatitis B as a surrogate marker for infant immune response to vaccination. iii. protective benefit against infections. iv. impact on growth and safety.

Methods: This double-blind, placebo-controlled randomized clinical trial involved 253 infants with a family history of allergic disease. Infants received at least 60ml of milk formula with or without probiotic (Bifidobacterium longum [BL999] 1?10*7 cfu/g and Lactobacillus rhamnosus [LPR] 2?10*7 cfu/g) daily for the first 6 months. Clinical evaluation was performed at 1, 3, 6, 12 and 24 months of age, with skin prick tests conducted at the 12 and 24 months. Serum samples were collected from cord blood and at 12 month visit to determine total immunoglobulin E and Hepatitis B virus surface antibody.

Results: Cumulative incidence of eczema in the probiotic (22%) group was similar to placebo (26%) at 2 years of age (adjusted odds ratio ORadj=0.73; 95% confidence interval CI=0.39 to 1.34). Prevalence of allergen sensitization showed no difference (18.6% vs. 18.9% in placebo, ORadj=0.92; 95% CI= 0.46 to 1.84). No difference in the incidence rate of asthma (probiotic=8.9% vs placebo=9.1%, ORadj=1.15; 95% CI=0.46 to 2.87) and allergic rhinitis (1.61% vs. 2.48% in the placebo, p=0.86) between the two groups was observed.

Improvement in Hepatitis B surface antibody responses in subjects receiving monovalent doses of Hepatitis B vaccine at 0, 1 month and a DTPa-Hepatitis B combination vaccine at 6 months [placebo:187.97 (180.70?195.24), probiotic:345.70 (339.41?351.99) mIU/ml] (p=0.069) was demonstrated, but not in those who received 3 monovalent doses [placebo:302.34 (296.31?308.37), probiotic:302.06 (296.31?307.81) mIU/ml] (p=0.996).

The rates of infections were similar. However, 3.94 times more infants were hospitalized due to infections during the first 6 months in the probiotic group (95% CI=1.21 to 12.75, p=0.022) but this difference was not observed later. Adequate growth was observed with a trend of consistently higher BMI in the probiotic group.

Conclusion: Early life administration of a cow?s milk formula supplemented with probiotics showed no effect on prevention of allergic diseases in the first 2 years of life in Asian infants at risk of allergic disease. However, probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules. Despite increase hospitalization due to infections, better growth was observed in the probiotic group. Further work is needed to determine whether timing of supplementation, dose and probiotic strain are important considerations. The role and complexities of interaction between the early microbial environment and the developing immune system needs to be unravelled before any recommendations for use in the paediatric population.