Correspondence

Effect of probiotic supplementation duringpregnancy and breast-feeding on the allergicsensitization in the infantile eczema

To the Editor:We readwith great interest the article by Rautava et al1 in which

they investigated the role of probiotic intervention regimens in re-ducing the risk of eczema in infants. Mothers with a history ofallergic disease and atopic sensitization were randomly assignedto the Lactobacillus rhamnosus LPR and Bifidobacterium longumBL999 (LPR1BL999) group, the Lactobacillus paracaseiST11 and B longum BL999 (ST111BL999) group, or the placebogroup during 2 months before and after the expecteddate of delivery. The authors followed all the infants until theage of 24 months and performed regular clinical examinationsscheduled at 1, 3, 6, 12, and 24 months to identify any caseof eczema. In addition, they performed skin prick tests at 6,12, and 24 months to confirm, if any, the diagnosis of atopicsensitization. Ultimately, they found that infants of mothersreceiving any of the probiotic supplements developed signifi-cantly less episodes of eczema when compared with the placebogroup. Skin prick test results, however, were similar betweenthe groups. We have several concerns regarding the interpretationof these results.Among children who sustain an episode of atopic dermatitis

during the first 2 years of life, more than 50% do notdemonstrate any signs of IgE sensitization. This condition isusually defined as nonatopic eczema, and these children becomesensitized during the course of atopic dermatitis.2 AlthoughRautava et al1 demonstrated a significant decrease in the inci-dence of clinical eczema in children whose mothers receivedany of the probiotic supplements; we believe that because ofthe relatively short follow-up time (2 years) the results maynot be extrapolated to other allergic conditions such as asthmaand allergic rhinitis.Given the similarity of the skin prick test results between the

study groups, one may say that Rautava et al’s study reflects adecreased incidence for nonatopic eczema rather than atopiceczema in children whose mothers received any of theprobiotic supplements. Atopic and nonatopic eczema do notevenly influence the development of allergic disorders in thelong term. Early atopic sensitization plays an important role inthe prognosis of atopic dermatitis. In a study by Illi et al,2

children with atopic dermatitis and a negative allergen sensiti-zation were followed until the age of 7 years and were demon-strated not to experience any signs of wheezing or bronchialhyperactivity. To conclude, the result of this study is limitedby the fact that it demonstrates the beneficial effects of probi-otic supplementation on nonatopic eczema but not atopiceczema.

Ahmet Z€ulfikar Akelma, MDa

Emin Mete, MDa

Bulent Bozkurt, MDb

From athe Division of Pediatric Allergy, Department of Pediatrics, and bthe Division of

Allergy, Department of Pulmonology, Fatih University School of Medicine, Ankara,

Turkey. E-mail: akelma@gmail.com.

Disclosure of potential conflict of interest: The authors declare that they have no relevant

conflicts of interest.

REFERENCES

1. Rautava S, Kainonen E, Salminen S, Isolauri E. Maternal probiotic supplementation

during pregnancy and breast-feeding reduces the risk of eczema in the infant.

J Allergy Clin Immunol 2012;130:1355-60.

2. Illi S, von Mutius E, Lau S, Nickel R, Gruber C, Niggemann B, et al. The natural

course of atopic dermatitis from birth to age 7 years and the association with asthma.

J Allergy Clin Immunol 2004;113:925-31.

Available online March 26, 2013.http://dx.doi.org/10.1016/j.jaci.2013.01.055

Reply

To the Editor:WethankAkelmaet al1 for their valuable comments regardingour

article.2 The authors touch upon 3 vitally important and intertwinedmatters that require further elucidation. Our understanding of thecausal interactions leading to atopic sensitizationandclinicaldiseaseis by no means satisfactory. These shortcomings continue to be re-flected in the nomenclature of atopic disease. Last, we need to reachclarity on what may be considered to constitute a preventive effect.The complex causal interactions between allergen exposure,

sensitization, and clinical hypersensitivity remain elusive. Tran-sient asymptomatic antigen-specific IgE sensitization is commonin infants andmay be encountered in up to 80% of children duringthe first 5 years of life3 while concomitantly exposure to allergenssensitizing the host immune system may not necessarily induceclinical disease.4 As Akelma et al1 allude, infants with eczemahave compromised skin and gut barriers that may function as por-tals for sensitization to environmental and dietary allergens. Littleprogress in elucidating these matters has been made since we lastdiscussed them in detail5 and therefore, as of present, we do notwish to argue as to which is the hen and which is the egg in thedevelopment of atopic disease.We hope that these questions attract scientific interest and

validated diagnostic and prognostic markers will be available forfuture clinical research. Meanwhile, we strongly believe that arigorously defined study population and clear-cut clinical diag-nostic criteria togetherwith sufficient duration of follow-up remainthe cornerstones for reliability, reproducibility, and clinical rele-vance in clinical trials aiming to reduce eczema risk. The diagnosisof eczema should, in our opinion, always be based on serial clinicalassessment by a physician and not on questionnaires or parentalreports alone. In a similar fashion, the probiotic interventionshould be described comprehensively including strains, theiridentity and culture collection deposit numbers, dose, duration,matrix, and viability to render the trial reproducible.We strongly agree with Akelma et al on the importance of a

sufficient follow-up period. Currently, there are no recommen-dations concerning proper follow-up time in the primary preven-tion of atopic disease but the highest incidence of eczema occursduring the first 2 years of life. In the previous probiotic interven-tion studies within our research program, follow-up periods of aminimumof 4 years and up to 14 years have been reached.We andrecently others have shown that the beneficial effects of earlyprobiotic intervention aiming to reduce eczema risk achievedduring the first 2 years of life persist later in childhood.6,7 Wetherefore believe that our results reflect a true preventive effect.While we are awaiting a more thorough understanding of the dis-ease entities at hand and, as a consequence, better diagnostic andprognostic markers, clinical follow-up of the present population

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