Probiotic Effects in Infants Last Until 4 Years of Age

Jennifer Garcia

February 10, 2012

February 10, 2012 — Infants exposed to Lactobacillus rhamnosus through diet supplements from 35 weeks' gestation through 2 years of age had a significantly lower risk for eczema and rhinoconjunctivitis. The protective effect lasted until the children were at least 4 years of age, according to a study published online February 6 in Clinical and Experimental Allergy.

The researchers, led by Kristin Wickens, PhD, from the Wellington Asthma Research Group, Wellington School of Medicine and Health Sciences, University of Otago, New Zealand, and colleagues, followed 425 infants for 4 years after daily supplementation with L rhamnosus (HN001; 6 × 109 colony-forming units [cfu]/day), Bifidobacterium animalis subsp lactis (HN019; 9 × 109 cfu/day), or placebo. Mothers received supplements from 35 weeks' gestation until their child's birth, continuing to 6 months after birth if they were breast-feeding, and all infants received supplements from birth until age 2 years.

The cumulative prevalence of eczema by age 4 years was significantly reduced in the children taking HN001 (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39 - 0.83) compared with in the children in the placebo group. The prevalence of rhinoconjunctivitis at age 4 years (relative risk, 0.38; 95% CI, 0.18 - 0.83) was also significantly reduced in the children in the HN001 group compared with in the children in the placebo group. HN019 did not affect the prevalence of any outcome relative to placebo.

"There have been a number of primary prevention studies investigating the effects of different species of probiotics taken by pregnant or breastfeeding mothers and/or their infants on the prevalence of eczema and sensitization by age 2 years. Reaching a consensus on the role of probiotics as primary preventers of allergic disease has been hampered by heterogeneity between studies in probiotic species and dose, duration and timing of intervention, and definitions of outcomes measured," the authors write.

The researchers previously published the initial results of their double-blind, randomized, placebo-controlled trial, in which they evaluated the effect of the probiotics on allergic disease and atopic sensitization in children in the first 2 years of life, in the October 2008 issue of the Journal of Allergy and Clinical Immunology (2008;122:788-794). That analysis demonstrated a 49% reduction in eczema prevalence in children receiving HN001 supplementation.

The current analysis demonstrates that the benefits of  HN001 persist to age 4 years, despite cessation of therapy 2 years earlier, suggesting that this probiotic might be an appropriate preventative intervention for high-risk infants.

The researchers collected data regarding the presence (since the child turned 2 years old) of eczema and any history of asthma or hay fever. They assessed eczema severity using the Scoring Atopic Dermatitis (SCORAD) scale, with a cutoff of 10 or higher, and performed skin-prick tests on the child's forearm in accordance with the Australasian Society of Clinical Immunology and Allergy guidelines. They also evaluated the prevalence of current asthma symptoms, using standard International Study of Asthma and Allergies in Childhood questions.

In addition to significantly reducing the risk of eczema by 4 years of age, the use of the HN001 probiotic also provided some protection against SCORAD≥10, wheeze, and atopic sensitization by age 4 years. However, the protective effects did not reach statistical significance.

Fecal samples from a subset of children (n = 153) were analyzed using real-time polymerase chain reaction for the presence of L rhamnosus and B animalis. The researchers noted that HN019 was not detectable in the feces, but HN001 (or HN001-like strains) was detected in 33% of children.

The researchers had previously shown that there was no difference between study groups for sex, ethnicity, delivery, birth weight, length and head circumference, breast-feeding duration, smoking in pregnancy or in the household, pet ownership, family history of allergic disease, or antibiotic use before age 2 years.

Some of the children (24%) had received nonstudy commercially available probiotic supplements; however, exclusion of these children from the analysis did not alter relative risk estimates.

The authors acknowledge study limitations such as the unblinding of participants after 2 years of age, which may have biased responses to questions about eczema frequency and severity. The misclassification of infectious rhinitis as allergic rhinitis and asthma at 4 years of age may also have affected the results, but the authors report that this would not have had a significant effect on the study findings.

"Ours is the only study to separately evaluate two different probiotics, and show an effect for HN001 but not HN019. The different effects we found for each probiotic at age 2 years persisted to 4 years, highlighting the importance of the particular probiotic in allergic disease prevention. Another strength of our study is the high response rate (>86% of eligible infants in each group) and follow-up beyond infancy," Dr. Wickens and colleagues write.

"The precise pathways for effects [of probiotics] on allergic disease remain elusive and require more work, including the possibility that effects are mediated via epigenetic mechanisms," conclude the authors.

Support for this study was provided by Fonterra Cooperative Group, New Zealand. One coauthor is supported by Cure Kids. The other authors have disclosed no relevant financial relationships.

Clin Exp Allergy. Published online February 6, 2012. Abstract


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