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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 ri ghts reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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ages years, rs, res respec pectiv tively ely.. The intr introdu oducti ction on of ages of 2, 3, and 4 yea cow’s milk, hen’s egg, peanuts, tree nuts, soy, and gluten  before  befor e the age of 6 mont months hs was not signi 󿬁cantly associa soc iated ted wit with h ec ecze zema ma or whe wheez ezing ing at any age af after ter adjustment for potential confounders, including gender, socioeconomic socioec onomic status of the mother, race/e race/ethnicity thnicity,, smokin smo king g dur during ing preg pregnan nancy, cy, ges gestati tational onal age at bir birth, th,  birth weight, parity, breastfeeding, and parental history of at atopy opy.. Adj Adjust ustme ments nts we were re ma made de fo forr ad addi ditio tiona nall

The im The impa pact ct of bi birt rth h or orde derr wa wass ex exam amin ined ed fo forr 11 45 454 4 children with known birth order. FA was categorized as current (at the time of survey) or past; FA during infancy wass de󿬁ned acc wa accord ording ing to sym sympto ptomat matic ic FA wit with h av avoid oidanc ance e 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

confounders between ages 12 and 24 months: use of any anti antibiot biotics, ics, day care atte attendan ndance, ce, gast gastroen roenteri teritis, tis, numbe num berr of re respi spirat ratory ory tra tract ct inf infec ectio tions, ns, and be being ing overweight (P   .   .10 for all comparisons). The results did not differ after stratifying child ’s history of cow ’s milk allergy and parental history of atopy.

to compa compare re dise disease ase prev prevalen alence ce betwe between en diffe different rent birth order groups. Adjustments were made for confounding variable vari ables, s, inclu including ding age age,, gend gender, er, gesta gestationa tionall age, birth weight, weig ht, nutrit nutrition ion durin during g infa infancy, ncy, day care attendance attendance  before age 1 year, and family history of allergic disease.


study di study did d no nott de demo mons nstr trat ate e th that at the timing timin g of introduction of alle allergeni rgenicc foods (cow’s milk, hen’s 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 allergen lerg enic ic fo foods ods in into to th the e in infa fant nt di diet et ca can n mo modi dify fy ri risk sk of at atop opic ic disease in children has not been established. This study is limited limite d by the ret retros rospec pectiv tive e nat nature ure of par parent ental al que quesstionnaires on the timing of allergenic food introduction and reliance on parental report of physician-diagnosed eczema and wheezing. In addition, the authors did not descri des cribe be the pre preval valenc ence e of sol solid id foo food d int introd roduct uction ion bef before ore 4 months mon ths of age age,, whi which, ch, in pre previo vious us stud studie ies, s, has been shown to be a risk factor for atopic disease. The authors ackn ac know owle ledg dge e the po pote tent ntia iall fo forr re reve vers rse e ca caus usat atio ion n as a confounding factor. Nonetheless, this was a large prospective study drawn from the general population, limiting selection bias. URL:–2183G

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

RESULTS.   Fi Firs rstt-bo born rn

childr chil dren en we were re les esss li like kelly to be comple com pletel tely y bre breast astfed fed duri during ng inf infanc ancy y and les lesss lik likely ely to attend day care before age 1 year compared with later born children. Birth order did not affect the incidence of atopic derma dermatitis titis or bronch bronchial ial asthma. Wheezing Wheezing in infancy was signi󿬁cantly higher among second-, third-, and la late ter-b r-born orn chi childr ldren en com compar pared ed wit with h   󿬁rst-born childr chi ldren. en. Inc Increa reasin sing g bir birth th ord order er was ass associ ociate ated d with a statist statisticall ically y signi󿬁cant decrease in prevalence of AR, AC, an and d FA in ch child ildhoo hood d an and d inf infan ancy. cy. The rel relati ation on  between birth order and FA showed a decreasing trend in preva prevalence lence between   󿬁rst-, second-, and thirdthird-born born children (4%, 3.4%, and 2.6%, respectively). Prevalence of late FA, early tolerant FA, and prolonged FA was signi 󿬁cantly lower in second-, third-, and later-born children childr en compa compared red with   󿬁rst-bor rst-borns. ns. Highe Higherr preva prevalence lence remained consistent for   󿬁rst-born children when speci󿬁c foods were examined. CONCLUSIONS.   The

prevalence of atopic dermatitis prevalence dermatitis and bronchial as chial asthm thma a wa wass not af affe fect cted ed by bi birth rth or orde derr whe wherea reass the prevalence of AR, AC, and FA decreased with increasing birth order. A reverse trend was demonstrated for wheezing in infancy. REVIEWER COMMENTS.  This

Birth Order Effect on Childhood Food Allergy Kusunok Kusu nokii T, Mu Muka kaid ida a K, Mori Morimo moto to T, et al al.. Pediatr Allergy Immunol . 2012;23(3):250–254 PURPOS PUR POSE E OF THE STU STUDY. DY.   To

determine determ ine the rel relati ationsh onship ip 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 chi childr ldren en to exa examin mine e pre preval valenc ence e of all aller ergi gicc rhinitis (AR), atopic dermatitis in childhood and infancy, allergi all ergicc conju conjunctiv nctivitis itis (AC), bron bronchia chiall asthm asthma, a, food all allergy ergy (FA) in childhood and infancy, and wheezing in infancy.

cross-sectional examination found a sig signi ni󿬁cant protective effect effect of increasing birth order on some allergic diseases (AR, AC, and FA); however, thiss eff thi effect ect was not obs observ erved ed for all all allerg ergic ic dis disord orders ers.. Limitations of the study included parental recall bias, lack of co con n󿬁rmat rmation ion of diag diagnose noses, s, and limited knowledge knowledge of pregna pre gnancy ncy and bir birth th his history tory of sub subjec jects ts inv involv olved. ed. The trend of decreasing prevalence of FA among later-born children childr en remai remained ned consist consistent ent regar regardless dless of past versus curre cur rent nt FA, ea early rly-- ve versu rsuss la late te-on -onset set FA, and ea early rly tolerant versus persistent FA, and was independent of the foo food d all allerg ergen. en. The These se   󿬁ndi ndings ngs sug sugges gestt tha thatt fut future ure studies should prospective prospectively ly examine maternal/fetal maternal/fetal immunolo immu nologic gic chan changes ges duri during ng   󿬁rst an and d sub subse seque quent nt pregnancies pregna ncies,, the impac impactt of mater maternal nal exposures during 󿬁rst and subsequent pregnancies, and the immunologic

PEDIATRICS Volume 130, Supplement 1, October 2012

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effect of early childhood exposures to allergens and/or pathogens pathog ens on   󿬁rst-born versus later-born siblings.

had odds rat ratios ios of 3.3 and 13. 13.2 2 for breastfe breastfeedi eding ng   ,4 months and .4 months respectively. respectively.



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

effects of breastfeeding on FS are modi󿬁ed by SNPs in the IL-12 beta receptor, TLR9, and TSLP genes, gen es, bot both h ind indivi ividua dually lly and joi jointly ntly.. The These se   󿬁ndings undersc unde rscore ore the imp import ortanc ance e of con consid sideri ering ng ind indivi ividua duall genetic genet ic varia variations tions in assess assessing ing this rela relationshi tionship. p. often ofte n ha have ve pe pedi diat atri rici cian anss an and d allergists confronted a distraught mother who feels she did di d ev ever eryt ythi hing ng to av avoi oid d al alle lerg rgic ic di dise seas ase e in he herr yo youn ung g ch chil ild d  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 pri prior or stu studie diess reg regard arding ing the all allerg ergy-p y-prev revent ention ion  bene󿬁ts of breastfeeding have yielded mixed results. REVIEWER REVIE WER

Gene Polymorphisms, Breastfeeding, and Development Develo pment of Food Sensitization Sensitization in Early Childhood Hong X, Wang G, Liu X, et al.  J Allergy Clin Immunol . 2011;128(2):374–381 PURPOS PUR POSE E OF THE ST STUDY UDY..   This This

study stud y lo look oked ed at th the e ef effe fect ct of  breastf  bre astfeed eeding ing on the dev develop elopmen mentt of food sen sensiti sitivit vity y (FS) and explored whether this relationship was modi󿬁ed by an array arr ay of func functiona tionall sing single le nucl nucleoti eotide de poly polymorp morphism hismss (SNP (SNPs). s). study inc includ luded ed chi childr ldren en fro from m the Boston Bos ton Bir Birth th Coh Cohort, ort, con consis sisting ting of mul multie tiethni thnic, c, pre pre-dominantly African American mother-infant pairs, participating in a postnatal children’s heal health th study assessing assessing growth,, devel growth developmen opment, t, and healt health h outcome outcomes. s.



James R. Banks, MD Timothy Andrews, MD


METHODS.   Fo Foll llow ow-u -up p vi visi sits ts we were re sc sche hedu dule led d at 6 to 12 mo mont nths hs

and 2, 4, an and and d 6 ye year ars, s, wi with th bl bloo ood d sa samp mple less ob obta tain ined ed at these tim times. es. Bre Breast astfee feedin ding g his history tory was obt obtain ained ed with a standardized questionnaire. FS was de󿬁ned as speci󿬁c 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 us ed to te test st th the e ef effe fect ctss of br brea east stfe feed edin ing g an and d ge gene ne- breastfeeding interactions on FS. children childr en (n   5   970) 970) wer were e follow followed ed for an averag ave rage e of 2.5   6   2.2 yea years. rs. Ove Overal rall, l, 37. 37.2% 2% had FS, RESULTS.   The

76.0% were ever breastfed, and 21.0% were exclusively  breastfed for at least 4 months. The T he prevalence of FS F S 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 tha than n nev never er bre breast astfed fed chi childr ldren. en. The per percen centag tages es 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 signi󿬁cant gene-breastfeeding interaction. Children carrying the GT/TT genotype for an SNP in the IL-12 rece re cept ptor or be beta ta ge gene ne ha had d a de decr crea ease sed d ri risk sk of FS (od (odds ds rati ra tio o 0. 0.6), 6), but th those ose with the GG ge geno noty type pe fo forr th that at SNP SN P ha had d an in incr crea ease sed d ri risk sk of FS (o (odd ddss ra rati tio o 2. 2.0) 0).. Similar interactions were observed for SNPs in Toll-like recept rec eptor or 9 (TLR (TLR9) 9) and thy thymic mic str stroma omall lym lymphop phopoie oietin tin (TSLP (T SLP). ). Mo Most st str strik ikin ing, g, in the gr group oup wi with th ex excl clus usiv ive e  breastfeeding, children carrying the TLR9 TT genotype



Arnold, MD

Parental Eczema Increases 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):77–83 PURPOS PUR POSE E OF THE STU STUDY. DY.   The The

authors inves investigate tigated d whethe whetherr history his tory of par parent ental al ato atopic pic dis diseas eases es are ass associ ociate ated d with a higher risk of reaction to common allergenic foods in children. STUDY POPULATION.  In

this Dutch study, 396 children (251 male, mal e, 145 fem female ale)) wit with h sus suspec pected ted foo food d all allerg ergy y wer were e recruited from a pediatric allergy outpatient clinic. Median age was 5.4 years (range, 6 months to 17.8 years). METHODS.   Th The e

parents pare nts an and d ch chil ildre dren n we were re as aske ked d if the they y ea each ch had a pre previo vious us dia diagno gnosis sis of ast asthma hma,, all allerg ergic ic rhi rhinit nitis, is, atopic dermatitis, or (in the parents) food allergy. Children dre n wer were e ide identi nti󿬁ed as hav having ing foo food d sen sensit sitivi ivity ty thro through ugh an elevated ImmunoCap-speci󿬁c IgE (.0.35 kU/L) to cow’s milk, hen’s egg, peanut, or hazelnut. The children also underwent underw ent double double-blind -blind,, place placebo-cont bo-controlle rolled d 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 reacti rea ction on to eac each h foo food d test tested ed bet betwee ween n chi childr ldren en who whose se 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 cow ’s 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 Updated Information & Services

including high resolution figures, can be found at: http://pediatrics _1/S7.full.html 

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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  from at Indonesia:AAP Sponsored on December 3, 2012

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