Skip to main content
Top
Published in: Allergy, Asthma & Clinical Immunology 1/2022

Open Access 01-12-2022 | Food Allergy | Research

The association between early formula and reduced risk of cow’s milk allergy during the first three year of life: a Japanese cohort study

Authors: Kota Ikari, Junichiro Tezuka, Masafumi Sanefuji, Jiro Nakayama, Daisuke Nishima, Yuri Sonoda, Masanobu Ogawa, Masayuki Shimono, Reiko Suga, Satoshi Honjo, Koichi Kusuhara, Shouichi Ohga, The Japan Environment and Children’s Study (JECS) Group

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2022

Login to get access

Abstract

Background

Our recent observational study showed that regular consumption of cow’s milk (CM) formula during early infancy (3–6 months old) was associated with a reduced risk of CM allergy (CMA) at 12 months old. However, the long-term association is unclear. The present study was aimed to examine how long this inverse association persists after 12 months old.

Methods

This study used the dataset of an ongoing nationwide prospective cohort, the Japan Environment and Children’s Study, in which participants were registered between January 2011 and March 2014. We analyzed 65,568 children followed-up until 36 months old. The exposure factors were the consumption statuses of formula milk from 0–3, 3–6, and 6–12 months old. The primary outcome was the prevalence of CMA at 6, 12, 18, 24 and 36 months old. CMA was defined as an allergic reaction and sensitization to CM protein in an individual with no or limited intake of this protein at the evaluation time, combined with physician-diagnosed food allergy. Multivariable regression models were used to estimate the association between the periods of formula consumption and the prevalence of CMA.

Results

The prevalence of CMA increased with a peak of 1.51% at 18 months old and then declined to 0.79% at 36 months old. Formula milk from 3–6 months old was associated with a reduced risk of CMA throughout the first 3 years of life, although the extent of the reduction was mitigated with age (adjusted relative risk: [95% confidence interval]: 0.19 [0.10–0.34] at 12 months old, 0.23 [0.16–0.33] at 18 months old, 0.41 [0.26–0.64] at 24 months old, and 0.47 [0.26–0.80] at 36 months old). The association between early formula and CMA were observed in both children with and without eczema, but more prominent and long-lasting in the former than the latter.

Conclusions

Regular exposure to CM protein during infancy was associated with a reduced prevalence of CMA during early childhood. At present, however, this observational study does not necessarily encourage formula feeding, and randomized controlled trials are warranted to confirm the findings and their significance.
Appendix
Available only for authorised users
Literature
1.
go back to reference Yamamoto-Hanada K, Pak K, Saito-Abe M, Yang L, Sato M, Irahara M, et al. Allergy and immunology in young children of Japan: the JECS cohort. World Allergy Organ J. 2020;13: 100479.CrossRef Yamamoto-Hanada K, Pak K, Saito-Abe M, Yang L, Sato M, Irahara M, et al. Allergy and immunology in young children of Japan: the JECS cohort. World Allergy Organ J. 2020;13: 100479.CrossRef
2.
go back to reference Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(77–82): e1. Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(77–82): e1.
3.
go back to reference Onizawa Y, Noguchi E, Okada M, Sumazaki R, Hayashi D. The association of the delayed introduction of cow’s milk with IgE-mediated cow’s milk allergies. J Allergy Clin Immunol Pract. 2016;4(481–8): e2. Onizawa Y, Noguchi E, Okada M, Sumazaki R, Hayashi D. The association of the delayed introduction of cow’s milk with IgE-mediated cow’s milk allergies. J Allergy Clin Immunol Pract. 2016;4(481–8): e2.
4.
go back to reference Saarinen KM, Savilahti E. Infant feeding patterns affect the subsequent immunological features in cow’s milk allergy. Clin Exp Allergy. 2000;30:400–6.CrossRef Saarinen KM, Savilahti E. Infant feeding patterns affect the subsequent immunological features in cow’s milk allergy. Clin Exp Allergy. 2000;30:400–6.CrossRef
5.
go back to reference Peters RL, Koplin JJ, Dharmage SC, Tang MLK, McWilliam VL, Gurrin LC, et al. Early exposure to cow’s milk protein is associated with a reduced risk of cow’s milk allergic outcomes. J Allergy Clin Immunol Pract. 2019;7(462–70): e1. Peters RL, Koplin JJ, Dharmage SC, Tang MLK, McWilliam VL, Gurrin LC, et al. Early exposure to cow’s milk protein is associated with a reduced risk of cow’s milk allergic outcomes. J Allergy Clin Immunol Pract. 2019;7(462–70): e1.
6.
go back to reference Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733–43.CrossRef Perkin MR, Logan K, Tseng A, Raji B, Ayis S, Peacock J, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733–43.CrossRef
7.
go back to reference Sakihara T, Otsuji K, Arakaki Y, Hamada K, Sugiura S, Ito K. Randomized trial of early infant formula introduction to prevent cow’s milk allergy. J Allergy Clin Immunol. 2021;147(224–32): e8. Sakihara T, Otsuji K, Arakaki Y, Hamada K, Sugiura S, Ito K. Randomized trial of early infant formula introduction to prevent cow’s milk allergy. J Allergy Clin Immunol. 2021;147(224–32): e8.
8.
go back to reference Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–13.CrossRef Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–13.CrossRef
9.
go back to reference Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:276–86.CrossRef Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:276–86.CrossRef
10.
go back to reference Tezuka J, Sanefuji M, Ninomiya T, Kawahara T, Matsuzaki H, Sonoda Y, et al. Possible association between early formula and reduced risk of cow’s milk allergy: the Japan Environment and Children’s Study. Clin Exp Allergy. 2021;51:99–107.CrossRef Tezuka J, Sanefuji M, Ninomiya T, Kawahara T, Matsuzaki H, Sonoda Y, et al. Possible association between early formula and reduced risk of cow’s milk allergy: the Japan Environment and Children’s Study. Clin Exp Allergy. 2021;51:99–107.CrossRef
11.
go back to reference Kawamoto T, Nitta H, Murata K, Toda E, Tsukamoto N, Hasegawa M, et al. Rationale and study design of the Japan environment and children’s study (JECS). BMC Public Health. 2014;14:25.CrossRef Kawamoto T, Nitta H, Murata K, Toda E, Tsukamoto N, Hasegawa M, et al. Rationale and study design of the Japan environment and children’s study (JECS). BMC Public Health. 2014;14:25.CrossRef
12.
go back to reference Michikawa T, Nitta H, Nakayama SF, Yamazaki S, Isobe T, Tamura K, et al. Baseline profile of participants in the Japan environment and children’s study (JECS). J Epidemiol. 2018;28:99–104.CrossRef Michikawa T, Nitta H, Nakayama SF, Yamazaki S, Isobe T, Tamura K, et al. Baseline profile of participants in the Japan environment and children’s study (JECS). J Epidemiol. 2018;28:99–104.CrossRef
13.
go back to reference Wang Z. Converting odds ratio to relative risk in cohort studies with partial data information. J Stat Softw. 2013;55:1–1.CrossRef Wang Z. Converting odds ratio to relative risk in cohort studies with partial data information. J Stat Softw. 2013;55:1–1.CrossRef
14.
go back to reference Zhang J, Yu KF. What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA. 1998;280:1690–1.CrossRef Zhang J, Yu KF. What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA. 1998;280:1690–1.CrossRef
15.
go back to reference Du Toit G, Tsakok T, Lack S, Lack G. Prevention of food allergy. J Allergy Clin Immunol. 2016;137:998–1010.CrossRef Du Toit G, Tsakok T, Lack S, Lack G. Prevention of food allergy. J Allergy Clin Immunol. 2016;137:998–1010.CrossRef
16.
go back to reference Shoda T, Futamura M, Yang L, Yamamoto-Hanada K, Narita M, Saito H, et al. Timing of eczema onset and risk of food allergy at 3 years of age: a hospital-based prospective birth cohort study. J Dermatol Sci. 2016;84:144–8.CrossRef Shoda T, Futamura M, Yang L, Yamamoto-Hanada K, Narita M, Saito H, et al. Timing of eczema onset and risk of food allergy at 3 years of age: a hospital-based prospective birth cohort study. J Dermatol Sci. 2016;84:144–8.CrossRef
17.
go back to reference Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol. 2012;129:1187–97.CrossRef Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol. 2012;129:1187–97.CrossRef
18.
go back to reference Prescott SL, Smith P, Tang M, Palmer DJ, Sinn J, Huntley SJ, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol. 2008;19:375–80.CrossRef Prescott SL, Smith P, Tang M, Palmer DJ, Sinn J, Huntley SJ, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol. 2008;19:375–80.CrossRef
Metadata
Title
The association between early formula and reduced risk of cow’s milk allergy during the first three year of life: a Japanese cohort study
Authors
Kota Ikari
Junichiro Tezuka
Masafumi Sanefuji
Jiro Nakayama
Daisuke Nishima
Yuri Sonoda
Masanobu Ogawa
Masayuki Shimono
Reiko Suga
Satoshi Honjo
Koichi Kusuhara
Shouichi Ohga
The Japan Environment and Children’s Study (JECS) Group
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Food Allergy
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2022
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/s13223-022-00712-z

Other articles of this Issue 1/2022

Allergy, Asthma & Clinical Immunology 1/2022 Go to the issue