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Short Communication

Int Arch Allergy Immunol 2014;163:25–28 Received: May 3, 2013
Accepted after revision: October 7, 2013
DOI: 10.1159/000356338
Published online: November 16, 2013

Supplementation with Probiotics in the First 6
Months of Life Did Not Protect against Eczema and
Allergy in At-Risk Asian Infants: A 5-Year Follow-Up
Evelyn X.L. Loo a Genevieve V. Llanora b Qingshu Lu c, d Marion M. Aw a, b
Bee Wah Lee a, b Lynette P. Shek a, b
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, b University Children’s
Medical Institute, National University Hospital, c Department of Biostatistics, Singapore Clinical Research Institute, and
Center for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore

Key Words tion to inhalant allergens. Similar growth rates were ob-
Allergy · Probiotics · Eczema served in both groups. Conclusions: The supplementation
of probiotics in early childhood did not play a role in the pre-
vention of allergic diseases. Clinical/Key Message: Early-life
Abstract supplementation with probiotics did not change allergic
Background: Healthy gut microflora is essential for oral tol- outcomes at 5 years of age. © 2013 S. Karger AG, Basel
erance and immunity. A promising approach to preventing
allergic diseases in genetically at-risk infants is to introduce
administration of probiotics early in life when their immune
system is still relatively immature. Objective: In this follow- Introduction
up study, we aim to determine if early-life supplementation
with strains of probiotics has any long-term effect on allergic We previously reported that feeding with cow’s-milk
outcomes. Methods: We analyzed the charts and electronic formula supplemented with probiotics [Bifidobacterium
databases of the PROMPT (Probiotics in Milk for the Preven- longum (BL999) and Lactobacillus rhamnosus (LPR)] in
tion of Atopy Trial) study cohort. This cohort consisted of 253 the first 6 months of life in a cohort of Asian infants at risk
infants at risk for allergy who were administered cow’s milk for allergic disease did not prevent eczema or allergen
supplemented with or without probiotics from the first day sensitization in the first year of life [1]. Here, we report on
of life to the age of 6 months. The cohort was then followed the long-term effects on allergic outcomes at the age of 5
up until the children were 5 years old and clinical outcomes years.
were assessed. Results: Of the 253 children recruited into Briefly, the subjects were randomized to receive a
the study, 220 (87%) completed the follow-up. At the age of commercially available cow’s-milk formula supplement-
5 years, there were no significant differences between the ed with or without probiotics from birth to 6 months of
groups in the proportion of children who had developed any age. At follow-up visits from 1 month to 5 years of age,
asthma, allergic rhinitis, eczema, food allergy and sensitiza- subjects were assessed for allergic outcomes. Diagnoses of - 7/30/2015 6:24:33 AM

© 2013 S. Karger AG, Basel Correspondence to: Dr. Lynette P. Shek
1018–2438/14/1631–0025$39.50/0 Department of Paediatrics, Yong Loo Lin School of Medicine
National University of Singapore, NUHS Tower Block, Level 12
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4) 0.1 – 17.6 – 1.143.7 – 1.295).9 (0. tobacco smoke and pets.2) 1.8) 32 (26. number of siblings.2) 0. with a mean SCORAD (Scoring placebo) completed at least 1 follow-up assessment. 231 Atopic Dermatitis) score of 16. n (%) Probiotic Placebo RR (95% CI) p value (n = 124) (n = 121) Ever had eczema (n = 124) (n = 121) By year 1 26 (21.1 – 15.1) 51 (47.6 – 2.4) 0.1) 0.0) 1.2) 0.4 – 2.0) 41 (38.9 (0.9) 1.2) 0.8 (0.9 (0.0) 25 (20.6) 0. pleted the follow-up and those who were lost to follow- tion.470 By year 5 31 (25.2) 4 (3.39.4) 0.2) 32 (26.5) 0.2 – 3.3 in the placebo group (p = 0.1) 17 (14.0) 38 (31. differences in the baseline demographics and family his- lergy was diagnosed by a history of convincing symptoms tory of allergic disease between the subjects who com- of food allergy and the presence of IgE allergen sensitiza.1 (0.723 Blo t 5 (4.5 – 1.7/30/2015 6:24:33 AM 26 Int Arch Allergy Immunol 2014.5 – 1.0) 1.9) 19 (17.1) 1.8) 0.8 (0.1 – 3.8) 0. Comparison of incidence of atopic diseases by year up to the age of 5 years Clinical characteristics.0 (0.6 – 1.1) 13 (10.0) 0.3) 47 (43.3) 19 (17.8) 1.6) 3 (2.3) 1.8) 1.1159/000356338 Downloaded by: . food al.000 Sensitization to inhalant allergens At year 2 test (n = 118) (n = 111) Any sensitization 20 (16. There were also 220 (87%) until the age of 5 years.000 By year 2 2 (1.5) 0.163:25–28 Loo /Llanora /Lu /Aw /Lee /Shek             DOI: 10.0 (0. use of an.0 (0. Eczema 245 (97%) (124 receiving probiotics and 121 receiving severity was also similar.0 (0.9 (0.9 (0.2 – 2.0) 0.842 By year 4 20 (16. There were no significant history and clinical examination at yearly visits.7 – 1. Table 1. the to record potential sources of environmental exposure to probiotic and placebo groups did not differ significantly allergens such as day-care.4 – 1.1 (0. with regard to environmental factors.7) 1.1) 0.6) 1.9 (0. and were based on a detailed low-up to the age of 5 years.4) 1.584 asthma.1 (0.722 By year 5 26 (21.0) 4 (3. studies.2) 0.9) 0 NA 1.8) 1.000 By year 4 1 (0. allergic rhinitis and eczema were made by pedia.6 – 2.320 Ever had asthma (n = 124) (n = 121) By year 1 4 (3.9) 11 (9.1 (0.456 By year 3 30 (24.3) 0.769 By year 4 30 (24.681 By year 3 5 (4.1) 57 (52.6 – 1.593 Der p 46 (41.0) 30 (24.5 – 1.3) 0.763 Der f (not done) NA NA NA NA At year 5 test (n = 112) (n = 108) Any sensitization 55 (49.8) 1.9) 23 (19.6 – 1.4) 0.3) 0.7 (0.6 – 1. in the probiotic and placebo groups (see table 1).7) 1. Questionnaires were also administered at each visit up.543 By year 2 27 (21. subjects who had had any eczema since birth was similar Of the 253 subjects who were recruited into the study.2) 35 (28.2) 0.8 (0.000 By year 2 11 (8.1) 1.8 (0.000 Ever had allergic rhinitis (n = 124) (n = 121) By year 1 1 (0.415 Blot t 37 (33.3) 1.2 (0.0 (0.6 – 1.9) 1 (0.4 – 2.9) 0 NA 1.9 in the probiotic group (91%) completed follow-up until the age of 2 years and and 15.000 By year 5 1 (0. For those who completed the 5-year follow-up.223 Ever had food allergy since year 3 (n = 117) (n = 109) By year 3 1 (0. Compared to published no significant differences between the probiotic group 198.000 By year 3 15 (12.3) 8 (6.4) 0. The proportion of tibiotics.9) 0.483 Der f 44 (39.5) 0.5 – 1. this is the largest cohort to have completed a fol- tricians in the research team.2) 6 (5.000 By year 5 16 (12.7) 1.7 (0.000 Der p 18 (15.8) 0.4) 1.000 By year 4 9 (7.2) 0.97 .8) 1 (0.3) 0.3 – 4.8 (0.2) 0.

the 2 bacterial strains we biotics compared with 8 of 18 (44. as respiratory allergies such as asthma.97 .002).7/30/2015 6:24:33 AM Early-Life Supplementation with Int Arch Allergy Immunol 2014.996) gain were similar in the 2 groups. farinae.660) and height (p = dophilus was not found to exhibit long-term protective 0. 3] while oth.1159/000356338 Downloaded by: . The protective effect of L. preciated. comes at 5 years of age. i.2–0.and the placebo group in the proportion of subjects who allergic rhinitis and sensitization to inhalant allergens of- had developed asthma (defined by 3 episodes of wheeze) ten manifest later in life.4%) who did not receive used in our study may have had a possible antagonistic probiotics [adjusted RR 0. Healthy gut microflora is essential for oral tolerance and immunity.593) was also similar in the 2 groups.154) with regular consumption of probiotics. rhamnosus in decreasing practice was statistically associated with a reduced inci. whether or not without probiotics as well as the assistance of the PROMPT probiotics indeed have a beneficial effect in the preven.8). In addition. another study [3]. there was no re. We also did not observe any difference in (CI) 0.3%) subjects who had a weekly consumption of pro. this is in line with (15. The growth rates ple. very few studies have looked at the long-term effects of probiotics on allergic diseases [5]. In contrast. voluntary participation of all subjects in this study is sincerely ap- ies have shown the prevention of eczema [2. the study by It was noted that a large number of subjects (208/226 Kalliomaki et al. or allergic rhinitis (see table 1). Those with symptomatic allergic rhi.4 and 95% CI 0. length and BMI be- RR 0.39. the possibility that these observations gic diseases. [6] showed a significantly decreased cu- or 92%) continued to consume probiotics of their own mulative risk for the development of eczema with the use accord in the form of milk formula/food/supplements of the L. A promising approach to preventing al- lergic diseases in genetically at-risk infants is to introduce Acknowledgments probiotics to them early in life when their immune system We acknowledge Nestlé for providing milk formula with and is still relatively immature [2].9%) subjects not receiving probiotics (adjusted nificant differences in birth weight. The incidence of asthma was tween infants who received Bifidobacterium lactis-sup- found to be associated with duration of feeding with pro.e.4%) with a regular consumption of probiotics and in a pooled analysis of previous trials which showed no sig- 7 of 18 (38. However. duction noted in the rate of eczema (RR 0. our study suggests that later and long-term rhinitis. Another study recently reported that infants may in part have been confounded by reverse causality who received probiotic supplementation between 2 and cannot be excluded.2–0. Blomia tropicalis or D. Incidentally. early-life supplementation with Lactobacillus aci- as well as the rate of weight (p = 0. However. This work was funded by the National Medical Re- ers do not find a reduction in allergic outcomes [4]. The tion of allergic diseases remains controversial. Other studies using different bac- goides pteronyssinus. probiotics or prenatal supplementation as well as the dose of probiotics placebo.143. 198. p = terial strains have also demonstrated no effect. (Probiotic in Milk for the Prevention of Atopy Trial) team. this bo. fects observed by some groups could be the inclusion of ment for a subject’s treatment group. for exam- 0. A possible reason for the protective ef- Calculations of relative risk (RR) were made with adjust. but this was not observed for allergic Interestingly. Some stud. the cumulative prevalence of eczema was also reported in dence of asthma and allergic rhinitis at the age of 5 years.163:25–28 27 Probiotics in At-Risk Infants DOI: 10. Singapore (NMRC/0890/2004 and NMRC/CSA/ 022/2010). eczema and allergen sensitization (data not probiotic supplementation could reduce the risk of aller- shown). biotics (p = 0. early-life supplementation with probi- 0. The proportion of subjects In our cohort. addition. 16 days after birth until 2 years of age had a significantly nitis and asthma may have been less proactive in their lower cumulative prevalence of eczema by the age of 4 consumption of probiotics. early supplementation in the first 6 who had experienced any food allergy (p = 1. years [9].8 and 95% CI In conclusion. In search Council. age of 5 years. It is critical to report the long-term effects of early-life supplementation with probiotics. otics did not change allergic outcomes in children at the gens (p = 0.543) or the sensitization to dust-mite aller. to specific bacterial strains [3].000) as well months of life with probiotics did not change allergic out- as those sensitized to dust-mite allergens (Dermatopha. A diagnosis of asthma was made in 36 of 208 administered. plemented infant formula and those that did not [8]. rhamnosus GG strain in a group of children in with probiotics at a frequency of at least once a week for their first 7 years compared to a group receiving a place- at least 1 year from the age of 2 years. effects on allergic outcomes [5].3–1.7]. p = 0.4 and 95% confidence interval effect [7]. Allergic rhinitis was diagnosed in 32 of 208 growth rate with the use of probiotics.9. Protective effects could also be attributed (17.

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