Birth Order Effect on Childhood Food Allergy Meredith A. Dilley and Tamara T. Perry Pediatrics 2012;130;S7 DOI: 10.1542/peds.

2012-2183H

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2012 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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ages of 2, 3, and 4 years, respectively. The introduction of cows milk, hens egg, peanuts, tree nuts, soy, and gluten before the age of 6 months was not signicantly associated with eczema or wheezing at any age after adjustment for potential confounders, including gender, socioeconomic status of the mother, race/ethnicity, smoking during pregnancy, gestational age at birth, birth weight, parity, breastfeeding, and parental history of atopy. Adjustments were made for additional confounders between ages 12 and 24 months: use of any antibiotics, day care attendance, gastroenteritis, number of respiratory tract infections, and being overweight (P . .10 for all comparisons). The results did not differ after stratifying childs history of cows milk allergy and parental history of atopy.
CONCLUSIONS. This study did not demonstrate that the

The impact of birth order was examined for 11 454 children with known birth order. FA was categorized as current (at the time of survey) or past; FA during infancy was dened according to symptomatic FA with avoidance of major food allergens at ,1 year of age. FA was further subdivided into the following: late FA (onset after age 1 year), early tolerant (gained oral tolerance before age 3 years), and prolonged FA (persistence of disease beyond age 3 years). Logistic regression models were used to compare disease prevalence between different birth order groups. Adjustments were made for confounding variables, including age, gender, gestational age, birth weight, nutrition during infancy, day care attendance before age 1 year, and family history of allergic disease.
RESULTS. First-born children were less likely to be completely breastfed during infancy and less likely to attend day care before age 1 year compared with laterborn children. Birth order did not affect the incidence of atopic dermatitis or bronchial asthma. Wheezing in infancy was signicantly higher among second-, third-, and later-born children compared with rst-born children. Increasing birth order was associated with a statistically signicant decrease in prevalence of AR, AC, and FA in childhood and infancy. The relation between birth order and FA showed a decreasing trend in prevalence between rst-, second-, and third-born children (4%, 3.4%, and 2.6%, respectively). Prevalence of late FA, early tolerant FA, and prolonged FA was signicantly lower in second-, third-, and later-born children compared with rst-borns. Higher prevalence remained consistent for rst-born children when specic foods were examined. CONCLUSIONS. The prevalence of atopic dermatitis and bron-

timing of introduction of allergenic foods (cows milk, hens egg, peanuts, tree nuts, soy, and gluten) was associated with eczema or wheezing in children aged #4 years.
REVIEWER COMMENTS. Whether timing of introduction of al-

lergenic foods into the infant diet can modify risk of atopic disease in children has not been established. This study is limited by the retrospective nature of parental questionnaires on the timing of allergenic food introduction and reliance on parental report of physician-diagnosed eczema and wheezing. In addition, the authors did not describe the prevalence of solid food introduction before 4 months of age, which, in previous studies, has been shown to be a risk factor for atopic disease. The authors acknowledge the potential for reverse causation as a confounding factor. Nonetheless, this was a large prospective study drawn from the general population, limiting selection bias.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20122183G

Faith Huang, MD Jennifer S. Kim, MD New York, NY

chial asthma was not affected by birth order whereas the prevalence of AR, AC, and FA decreased with increasing birth order. A reverse trend was demonstrated for wheezing in infancy.
REVIEWER COMMENTS. This cross-sectional examination found a signicant protective effect of increasing birth order on some allergic diseases (AR, AC, and FA); however, this effect was not observed for all allergic disorders. Limitations of the study included parental recall bias, lack of conrmation of diagnoses, and limited knowledge of pregnancy and birth history of subjects involved. The trend of decreasing prevalence of FA among later-born children remained consistent regardless of past versus current FA, early- versus late-onset FA, and early tolerant versus persistent FA, and was independent of the food allergen. These ndings suggest that future studies should prospectively examine maternal/fetal immunologic changes during rst and subsequent pregnancies, the impact of maternal exposures during rst and subsequent pregnancies, and the immunologic S7

Birth Order Effect on Childhood Food Allergy Kusunoki T, Mukaida K, Morimoto T, et al. Pediatr Allergy Immunol. 2012;23(3):250254
PURPOSE OF THE STUDY. To determine the relationship between birth order and the prevalence of allergic diseases in childhood. STUDY POPULATION. The study population included 11 454 children 7 to 15 years of age in Kyoto, Japan. METHODS. A validated survey was administered to parents of 14 669 children to examine prevalence of allergic rhinitis (AR), atopic dermatitis in childhood and infancy, allergic conjunctivitis (AC), bronchial asthma, food allergy (FA) in childhood and infancy, and wheezing in infancy.

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PEDIATRICS Volume 130, Supplement 1, October 2012

effect of early childhood exposures to allergens and/or pathogens on rst-born versus later-born siblings.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20122183H

had odds ratios of 3.3 and 13.2 for breastfeeding ,4 months and .4 months respectively.
CONCLUSIONS. The effects of breastfeeding on FS are mod-

Meredith A. Dilley, MD Tamara T. Perry, MD Little Rock, AR

ied by SNPs in the IL-12 beta receptor, TLR9, and TSLP genes, both individually and jointly. These ndings underscore the importance of considering individual genetic variations in assessing this relationship.
REVIEWER COMMENTS. How often have pediatricians and allergists confronted a distraught mother who feels she did everything to avoid allergic disease in her young child by adhering to breastfeeding and delaying the introduction of notoriously allergenic foods? We know now from other studies that the latter tactic is generally the wrong course, and this article might help us understand why prior studies regarding the allergy-prevention benets of breastfeeding have yielded mixed results.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.20122183I

Gene Polymorphisms, Breastfeeding, and Development of Food Sensitization in Early Childhood Hong X, Wang G, Liu X, et al. J Allergy Clin Immunol. 2011;128(2):374381
PURPOSE OF THE STUDY. This study looked at the effect of breastfeeding on the development of food sensitivity (FS) and explored whether this relationship was modied by an array of functional single nucleotide polymorphisms (SNPs). STUDY POPULATION. The study included children from the

Boston Birth Cohort, consisting of multiethnic, predominantly African American mother-infant pairs, participating in a postnatal childrens health study assessing growth, development, and health outcomes.
METHODS. Follow-up visits were scheduled at 6 to 12 months and 2, 4, and 6 years, with blood samples obtained at these times. Breastfeeding history was obtained with a standardized questionnaire. FS was dened as specic IgE of 0.35 kU/L or greater to any of 8 common food allergens (egg white, cow milk, peanut, soy, shrimp, walnut, wheat, and cod). Eighty-eight potentially functional SNPs were genotyped from 18 genes involved in innate immunity or TH1/TH2 imbalance. Logistic regression models were used to test the effects of breastfeeding and genebreastfeeding interactions on FS. RESULTS. The children (n 5 970) were followed for an average of 2.5 6 2.2 years. Overall, 37.2% had FS, 76.0% were ever breastfed, and 21.0% were exclusively breastfed for at least 4 months. The prevalence of FS was higher in breastfed children (39.6%) than in those never breastfed (29.4%). With adjustment for pertinent covariates, breastfed children were at 1.5 times higher risk for FS than never breastfed children. The percentages of ever and exclusive breastfeeding were similar in those with and without family histories of allergic disease. Of the 88 SNPs successfully genotyped, 5 revealed statistically signicant gene-breastfeeding interaction. Children carrying the GT/TT genotype for an SNP in the IL-12 receptor beta gene had a decreased risk of FS (odds ratio 0.6), but those with the GG genotype for that SNP had an increased risk of FS (odds ratio 2.0). Similar interactions were observed for SNPs in Toll-like receptor 9 (TLR9) and thymic stromal lymphopoietin (TSLP). Most striking, in the group with exclusive breastfeeding, children carrying the TLR9 TT genotype

James R. Banks, MD Timothy Andrews, MD Arnold, MD

Parental Eczema Increases the Risk of DoubleBlind, Placebo-Controlled Reactions to Milk but Not to Egg, Peanut, or Hazelnut van den Berg ME, Flokstra-de Blok BMJ, Vlieg-Boerstra BJ, et al. Int Arch Allergy Immunol. 2012;158(1):7783
PURPOSE OF THE STUDY. The authors investigated whether history of parental atopic diseases are associated with a higher risk of reaction to common allergenic foods in children. STUDY POPULATION. In this Dutch study, 396 children (251 male, 145 female) with suspected food allergy were recruited from a pediatric allergy outpatient clinic. Median age was 5.4 years (range, 6 months to 17.8 years). METHODS. The parents and children were asked if they each had a previous diagnosis of asthma, allergic rhinitis, atopic dermatitis, or (in the parents) food allergy. Children were identied as having food sensitivity through an elevated ImmunoCap-specic IgE (.0.35 kU/L) to cows milk, hens egg, peanut, or hazelnut. The children also underwent double-blind, placebo-controlled food challenges (DBPCFC) to the allergenic food, with a period of at least 2 weeks between food and placebo challenges. Logistic regression analysis was used to compare risk of a reaction to each food tested between children whose parents were not atopic and children with 1 or 2 parents with atopic diseases. RESULTS. More than 90% of the children had been previously diagnosed with atopic disease, most commonly eczema. A total of 553 DBPCFCs were performed with 274 children tested for 1 food, 92 for 2 foods, 25 for 3 foods, and 5 for all 4 foods. Foods tested included cows milk (n 5 185), egg (n 5 110), peanut (n 5 198), and

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Birth Order Effect on Childhood Food Allergy Meredith A. Dilley and Tamara T. Perry Pediatrics 2012;130;S7 DOI: 10.1542/peds.2012-2183H
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2012 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on December 3, 2012