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Multicenter Study
. 2026 Jan 2;9(1):e2554694.
doi: 10.1001/jamanetworkopen.2025.54694.

Parental Age and Childhood Allergy Risk

Kiwako Yamamoto-Hanada  1 , Daisuke Harama  2 , Miori Sato  2 , Yumiko Miyaji  2 , Kei Sakamoto  2 , Minaho Nishizato  2 , Limin Yang  2 , Natsuhiko Kumasaka  2 , Hidetoshi Mezawa  2 , Shintaro Iwamoto  3 , Kyongsun Pak  3 , Tomoki Nishizawa  4 , Kari C Nadeau  5 , Maki Fukami  2 , Yukihiro Ohya  1   6   7 ; Japan Environment and Children’s Study (JECS) Group
Collaborators, Affiliations
Multicenter Study

Parental Age and Childhood Allergy Risk

Kiwako Yamamoto-Hanada et al. JAMA Netw Open. .

Abstract

Importance: Allergic diseases in children are influenced by gene-environment interactions. Although advanced parental age has been associated with genetic and epigenetic changes, its relationship with childhood allergy risk remains unclear.

Objective: To examine the association between parental age at childbirth and the risk of allergic diseases in early childhood.

Design, setting, and participants: This nationwide, multicenter, population-based, prospective birth cohort study used data from the Japan Environment and Children's Study (JECS). Participants were enrolled at 15 regional centers in Japan between January 2011 and March 2014, with follow-up data collected at child ages 1, 2, and 4 years. The present analysis was conducted from July 8, 2024, to February 4, 2025. Eligible participants were singleton live births with data on parental age and allergic outcomes. Physician-diagnosed allergy outcomes were collected via parental report. House dust mite (HDM) sensitization was assessed in a subcohort.

Main outcomes and measures: The primary outcomes were physician-diagnosed food allergy, wheeze, asthma, and eczema at ages 1, 2, and 4 years. The secondary outcome was HDM sensitization at ages 2 and 4 years. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression after multiple imputation for missing values.

Results: A total of 34 942 mother-child pairs were included; the mean (SD) maternal age at entry was 31.0 (4.7) years, and 17 892 mothers (51.2%) had a medical allergy history. The prevalence of food allergy at age 1 year was 6.6% (95% CI, 6.4%-6.9%), decreasing with maternal age. Compared with children of mothers aged 25 to 29 years, those of mothers aged 35 to 39 years (OR, 0.79; 95% CI, 0.70-0.90) and aged 40 years and older (OR, 0.59; 95% CI, 0.44-0.79) had lower odds of food allergy. Children of parents both aged 35 years or older had lower odds of wheezing at age 4 years (OR, 0.89; 95% CI, 0.82-0.95). HDM was assessed in 1991 children at age 2 years and 1840 children at age 4 years, and children of older mothers also had lower odds of HDM sensitization (children of mothers aged 30-34 years, OR, 0.76; 95% CI, 0.59-0.98; children of mothers aged 35-39 years, OR, 0.68; 95% CI, 0.50-0.91).

Conclusions and relevance: In this cohort study of 34 942 mother-child pairs, children of older mothers had reduced odds of food allergy, wheezing, and HDM sensitization in early childhood, suggesting that advanced maternal age may be protective against the development of allergic diseases in early childhood.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yamamoto-Hanada reported receiving personal fees from AbbVie, B-Case, Eli Lilly and Company, Maruho, Otsuka Pharmaceutical, Pfizer, Pierre Fabre Japon, Regeneron Pharmaceuticals, Sanofi S.A., Santen Pharmaceutical, Sun Pharmaceutical Industries, and Takano; grants from AMED, the Japan Society for the Promotion of Science (JSPS), the National Center for Child Health and Development, the Nipponham Foundation for the Future of Food, the Urakami Foundation for Food and Food Culture Promotion, Alcare, B-Case, Fam’s, Kao Corporation, Natural Science, Otsuka Pharmaceutical, and Takano; and consultant fees from AbbVie, B-Case, Otsuka Pharmaceutical, Sanofi S.A., and Santen Pharmaceutical outside the submitted work. Dr Sato reported receiving personal fees from Sanofi K.K. and Torii Pharmaceutical outside the submitted work. Dr Nadeau reported receiving grants from National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, and National Institute of Environmental Health Sciences; consulting fees from Excellergy; stocks or stock options from Phylaxis and IgGenix; and being a national scientific committee member of the Immune Tolerance Network outside the submitted work. In addition, Dr Nadeau had a patent for granulocyte-based methods for detecting and monitoring immune system disorders issued, a patent for methods and assays for detecting and quantifying pure subpopulations of white blood cells in immune system disorders issued, a patent for biological sample preparation device and methods of using the same pending, a patent for immune cell activation device and methods of using the same pending, a patent for mixed allergen compositions and methods for using the same issued, and a patent for methods of isolating allergen specific antibodies, microfluidic device and diagnostic methods for basophil activation, and methods for detecting heavy metals in biological samples pending. Dr Ohya reported receiving grants from Fam, AMED, JSPS, and the National Center for Child Health and Development; and consulting or lecture fees from AbbVie, B-CASE, Kao, Kyowa Kirin, LEO Pharma A/S, Maruho, Otsuka Pharmaceutical, Sanofi S.A., Eli Lilly and Company, Ikeda Mohando, Kyorin Pharmaceutical, Regeneron Pharmaceuticals, Santen Pharmaceutical, Sun Pharmaceutical Industries, and Torii Pharmaceutical. No other disclosures were reported.

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