Risk Factors for the Development of Food Allergy in Infants and Children: A Systematic Review and Meta-Analysis.
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Islam Nazmul, Chu Alexandro W L, Sheriff Falana, Foroutan Farid, Guyatt Gordon H, Brignardello-Petersen Romina, Oykhman Paul, Iorio Alfonso, Izcovich Ariel, Morrison Katherine M, Roldan Benitez Yetiani, Couban Rachel J, Borovsky Dorota, Zhang Yiming, Ologundudu Leonardo, Pasumarthi Keerthana, Farooq Syed Fahad, Tong Kyle, Tang Wang-Choi, Faisal Haseeb, Khalid Muhammad Faran, Asif Mohammad Saad, French Shannon, Waserman Susan, Chinthrajah R Sharon, Sampson Hugh A, Mustafa S Shahzad, Lieberman Jay A, Järvinen Kirsi M, Bailey Sally, Bégin Philippe, Sicherer Scott H, Gerdts Jennifer, Carver Melanie, Mitchell Lynda, Cleary Kelly, Greenhawt Matthew J, Wang Julie, Anagnostou Aikaterini, Shaker Marcus S, Chandra-Puri Anita, Fulkerson Patricia C, Wood Robert A, Chu Derek K
Аннотация
OBJECTIVE: To estimate the incidence and quantify risk factors for food allergy development.
DATA SOURCES: MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.
STUDY SELECTION: Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.
DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds ratios (ORs). Risk of bias was assessed using the QUIPS tool, and certainty of evidence assessed using GRADE.
MAIN OUTCOME AND MEASURE: The primary outcome was food allergy to age 6 years.
RESULTS: A total of 190 studies involving 2.8 million participants across 40 countries were analyzed. Among studies using food challenge, overall food allergy incidence was likely 4.7% (moderate certainty). Among 176 studies identifying 342 risk factors with varying certainty, the strongest and most certain factors included prior allergic conditions (eg, atopic dermatitis [eczema] within the first year of life [OR, 3.88; risk difference [RD], 12.0%; 95% CI, 8.8%-15.7%], allergic rhinitis [OR, 3.39; RD, 10.1%; 95% CI, 6.7%-14.4%], and wheeze [OR, 2.11; RD, 5.0%; 95% CI, 2.1%-8.8%]), severity of atopic dermatitis (OR, 1.22; RD, 1.0%; 95% CI, 0.6%-1.6%), increased skin transepidermal water loss (OR, 3.36; RD, 10.0%; 95% CI, 6.3%-14.8%), filaggrin gene sequence variations (OR, 1.93; RD, 4.2%; 95% CI, 2.4%-6.4%), delayed solid food introduction (eg, peanut after age 12 months [OR, 2.55; RD, 6.8%; 95% CI, 1.9%-14.6%]), infant antibiotic use (first month [OR, 4.11; RD, 12.8%; 95% CI, 0.4%-40%], first year [OR, 1.39; RD, 1.8%; 95% CI, 0.8%-3.1%], during pregnancy [OR, 1.32; RD, 1.5%; 95% CI, 0.6%-2.5%]), male sex (OR, 1.24; RD, 1.1%; 95% CI, 0.7%-1.6%), firstborn child (OR, 1.13; RD, 0.6%; 95% CI, 0.3%-1.0%), family history of food allergy (eg, mother [OR, 1.98; RD, 4.4%; 95% CI, 2.5%-6.8%], father [OR, 1.69; RD, 3.2%; 95% CI, 1.3%-5.5%], both parents [OR, 2.07; RD, 4.8%; 95% CI, 1.3%-5.5%], siblings [OR, 2.36; RD, 6.0%; 95% CI, 4.4%-8.0%]), parental migration (OR, 3.28; RD, 9.7%; 95% CI, 4.9%-16.3%), self-identification as Black (vs White [OR, 3.93; RD, 12.1%; 95% CI, 5.2%-22.5%], vs non-Hispanic White [OR, 2.23; RD, 5.5%; 95% CI, 3.0%-8.7%]), and cesarean delivery (OR, 1.16; RD, 1.0%; 95% CI, 0.3%-1.2%). Factors like low birth weight, postterm birth, maternal diet, and stress during pregnancy showed no significant risk difference.
CONCLUSIONS AND RELEVANCE: In this meta-analysis, the most credible risk factors associated with development of childhood food allergy are a combination of major and minor risk factors, including early allergic conditions (atopic march/diathesis), delayed allergen introduction, genetics, antibiotic exposure, demographic factors, and birth-related variables.