Vaccination and allergic disease: a birth cohort study
Open accessAbstract
OBJECTIVES: We examined the effect of vaccination for diphtheria; polio; pertussis and tetanus; or measles, mumps, and rubella on the incidence of physician-diagnosed asthma and eczema. METHODS: We used a previously established birth cohort in the West Midlands General Practice research database. RESULTS: We found an association between vaccination and the development of allergic disease; however, this association was present only among children with the fewest physician visits and can be explained by this factor. CONCLUSIONS: Our data suggest that currently recommended routine vaccinations are not a risk factor for asthma or eczema.
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In McKeever 2004, there was a significant association between MMR immunisation and asthma only for the group with lower GP consultation during the first 6 live months (hazard ratio 7.18; 95% CI 2.95 to 17.49).
“Significant association only for the group with lower GP consultation during the first 6 live months (hazard ratio 7.18; 95% CI from 2. 95 to 17. 49)”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as McKeever 2004
Table 2 (Results; page not provided) reports an MMR–asthma hazard ratio of 7.18 (95% CI 2.95–17.49) for the lowest GP-consultation group; the other consultation strata have confidence intervals spanning 1. However, the MMR groups are based on consultations in the first 18 months, not the first 6 months. The six-month measure applies to DPPT. (LLM, conf=0.93)
Experimental — accuracy not yet measuredStratifying for GP consultation frequency in the first 18 months, HR estimates remain significant only for the subgroup with lower consulting frequency (zero to six times) and not for the other subgroups: HR 7.18 (95% CI 2.95 to 17.49) for asthma; HR 10.4 (95% CI 4.61 to 23.29) for eczema.
“Stratifying for GP consultation frequency in the first 18 months, HR estimates remain significant only for the subgroup with lower consulting frequency (zero to six times in the first 18 months) and not for the other subgroups (seven to 10 times, 11 to 16 times and more than 16 times): HR 7.18 (95% CI 2.95 to 17.49) for association between MMR vaccination and asthma; HR 10.4 (95% CI 4.61 to 23.29)”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as McKeever 2004
Estimates from McKeever 2004 (although significant) are strongly affected by ascertainment bias, as children who are not taken to the doctor are less likely to be vaccinated and also have fewer opportunities to have diagnoses of allergic diseases recorded.
“Estimates from McKeever 2004 (although significant) are strongly affected by ascertainment bias, as children who are not taken to the doctor are less likely to be vaccinated and also have fewer opportunities to have diagnoses of allergic diseases recorded.”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as McKeever 2004
The cohort study by McKeever 2004 found crude hazard ratios of 3.51 (95% CI 2.42 to 5.11) for asthma and 4.61 (95% CI 3.15 to 6.74) for eczema.
“Correspondent crude hazard ratios (HR) were 3.51 (95% CI 2.42 to 5.11) and 4.61 (95% CI 3.15 to 6.74) for asthma and eczema, respectively.”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as McKeever 2004
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Vaccines for measles, mumps and rubella in children
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“However, large and small studies have shown no association of vaccine status of children with changes in rates of atopic allergy or asthma in the United States (57) United Kingdom (55,58) and the Netherlands (59–61).”
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“Atopic disease was associated with early DTP vaccination in studies from the UK and Canada (9, 20), whereas data from a UK cohort reported no association between timing of DTP and asthma or eczema (21).”
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“Many vaccines stimulate the immune system, and may lead to allergic reactions (McKeever et al., 2004).”
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“Immunisation information for the MACS cohort was collected only on those immunisations on the schedule at the commencement of the study: DTP, CDT, Sabin and MMR, but not on BCG, H. influenzae, Pneumococcal, Meningococcal and Hepatitis B immunisation.”
ResultInfluentialTiming of routine infant vaccinations and risk of food allergy and eczema at one year of age
Kiraly, N. J., Koplin, J. J., Crawford, N. W., Bannister, S., Flanagan, K. L., Holt, P. G., Gurrin, L. C., Lowe, A. J., Tang, M. L. K., Wake, M. A., et al. (2015) · Allergy · doi:10.1111/all.12830 · Cited by 35 · see citing works
“Four of these studies investigated the whole-cell pertussis vaccine no longer used in most industrialized countries (13–16), only one investigated eczema (16) and none investigated food allergy.”
BackgroundInfluentialChildhood vaccination and allergy: A systematic review and meta‐analysis
Navaratna, S. N. K., Estcourt, M. J., Burgess, J. A., Waidyatillake, N. T., Enoh, E., Lowe, A. J., Peters, R. L., Koplin, J. J., Dhamage, S. C., & Lodge, C. (2021) · Allergy · doi:10.1111/all.14771 · Cited by 35 · see citing works
“Two publications based on the other RCT reported allergic outcomes following pertussis vaccination at 2, 4 and 6 months of age.29,30 TA B L E 1 Characteristics of the publications used for the qualitative synthesis (details on control group for cohort studies, sources of information etc given in Table S5) Reference, c…”
BackgroundInfluentialSpycher, B. D., Silverman, M. A., Egger, M., Zwahlen, M., & Kuehni, C. E. (2009) · PEDIATRICS · doi:10.1542/peds.2008-0115 · Cited by 33 · see citing works
Childhood immunization and atopic disease into middle-age - a prospective cohort study
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“One previous study of asthma and eczema incidence after DPPT and MMR vaccination in the UK found an increased incidence of both asthma and eczema after immunization (19).”
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“Other studies have similarly found decreased allergic outcomes following delayed DTP vaccination [41], while some suggest no such DTP effect [42].”
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“, 2003), the majority show no relationship (Stannegard et al., 1998; Henderson et al., 1999; Yilmaz et al., 2000; Gruber et al., 2001; Bager et al., 2003; Marks et al., 2003; Nilsson et al., 2003; Annus et al., 2004; Koppen et al., 2004; Maitra et al., 2004; McKeever et al., 2004; Mohrenschlager et al., 2007), and oth…”
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“On the other hand, allergenicity results revealed that four epitopes of phosphoprotein, three epitopes of polymerase, and two epitopes of nucleocapsid protein to be nonallergic and the rest were allergic which could induce T helper cells and IgE antibodies to over sensitize the host cells.(75) Three epitopes from phos…”
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“Likewise, putative vaccine candidates must be checked for allergenicity to prevent allergic responses in the host that may be caused by vaccination (McKeever et al., 2004).”
BackgroundIs childhood immunisation associated with atopic disease from age 7 to 32 years?
Nakajima, K., Dharmage, S. C., Carlin, J. B., Wharton, C., Jenkins, M. A., Giles, G. G., Abramson, M. J., Walters, E. H., & Hopper, J. L. (2006) · Thorax · doi:10.1136/thx.2006.062547 · Cited by 27 · see citing works
“[13-15] Similarly, conflicting evidence has been reported for other vaccines including diphtheria, tetanus and polio.[10, 13, 16-18] However, none of the studies have found any harmful effect for measles [10, 12, 13, 19], BCG [20-22] and smallpox vaccine [23, 24] on the development of atopic diseases.”
Environmental Factors and Allergic Disorders
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The relationship between vaccine refusal and self-report of atopic disease in children
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A computational approach to design a multiepitope vaccine against H5N1 virus
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“According to a criterion for predicting allergenicity, a sequence is deemed possibly allergenic if, when compared to known allergens, it shares the identity of at least six consecutive amino acids within an 80-amino acid window [38].”
BackgroundVaccinations in the first year of life and risk of atopic disease – Results from the KiGGS study
Schlaud, M., Schmitz, R., Poethko‐Müller, C., & Kuhnert, R. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.07.111 · Cited by 22 · see citing works
Pertussis Immunization in Infancy and Adolescent Asthma Medication
Vogt, H., Bråbäck, L., Kling, A., Grünewald, M., & Nilsson, L. J. (2014) · PEDIATRICS · doi:10.1542/peds.2014-0723 · Cited by 21 · see citing works
CytomegaloVirusDb: Multi-omics knowledge database for cytomegaloviruses
Khan, T., Khan, A., Nasir, S. N., Ahmad, S., Ali, S. S., & Wei, D. (2021) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2021.104563 · Cited by 20 · see citing works
Oany, A. R., Sharmin, T., Chowdhury, A. S., Pervin, T., & Hasan, M. A. (2015) · In Silico Pharmacology · doi:10.1186/s40203-015-0011-4 · Cited by 19 · see citing works
“Another important feature of the peptide vaccine is its allergen-icity (McKeever et al. 2004).”
BackgroundJanjanam, V. D., Mukherjee, N., Lockett, G. A., Rezwan, F. I., Kurukulaaratchy, R. J., Mitchell, F., Zhang, H., Arshad, H., Holloway, J. W., & Karmaus, W. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.10.068 · Cited by 19 · see citing works
“Conversely, the DPPT (Diphtheria, Polio, Pertussis, Tetanus) and MMR (measles, mumps, and rubella) vaccines were not linked with physician diagnosed asthma or eczema in children in one birth cohort study [11].”
BackgroundOany, A. R., Ahmad, S. A. I., Hossain, M. U., & Pervin, T. (2015) · Advances and Applications in Bioinformatics and Chemistry · doi:10.2147/aabc.s75250 · Cited by 19 · see citing works
Guidelines for allergy prevention in Hong Kong
Chan, W. M., Chan, J. K., Tam, A. Y., Leung, T., & Lee, T. H. (2016) · Hong Kong Medical Journal · doi:10.12809/hkmj154763 · Cited by 17 · see citing works
“There is no evidence to show that vaccination practices have any adverse effect on the incidence of allergic diseases in population-based cohort studies [120,121].”
BackgroundImmunological considerations regarding parental concerns on pediatric immunizations
Nicoli, F., & Appay, V. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.04.030 · Cited by 17 · see citing works
“3 Effect on atopic disorders and autoimmune diseases 94 Historically, vaccines have been proposed to be involved in the development of allergies, asthma and other 95 atopic disorders [65].”
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Khan, T., Khan, A., & Wei, D. (2021) · Database · doi:10.1093/database/baab063 · Cited by 16 · see citing works
“The performed allergenicity check helps to prevent any possible allergic responses in the host (69).”
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Vaccination and Allergic Sensitization in Early Childhood – The ALADDIN Birth Cohort
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“We also conclude, like McKeever et al. [23], that the total number of vaccinations given is not associated with allergic disease.”
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Gehrt, L., Rieckmann, A., Kiraly, N. J., Jensen, A. K. G., Aaby, P., Benn, C. S., & Sørup, S. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.09.024 · Cited by 11 · see citing works
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“Most of the present day vaccines activate the immune system into allergic state (McKeever et al., 2004) by inducing type 2 T helper T (Th2) cells and immunoglobulin E (IgE).”
Backgroundda Silva, M. K., Azevedo, A. A. C., Campos, D. M. D. O., de Souto, J. T., Fulco, U. L., & Oliveira, J. I. N. (2022) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2050301 · Cited by 11 · see citing works
“Similarly, putative vaccine candidates must be tested for allergenicity to prevent allergic reactions in the host that could be triggered by vaccination (McKeever et al., 2004).”
BackgroundAli, M. C., Khatun, M. S., Jahan, S. I., Das, R., Munni, Y. A., Rahman, M. M., & Dash, R. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1947381 · Cited by 10 · see citing works
BCG Vaccination in Early Childhood and Risk of Atopic Disease: A Systematic Review and Meta-Analysis
Zhao, K., Miles, P., Jiang, X., Zhou, Q., Cao, C., Lin, W., Hubbard, R., Fu, P., & Xu, S. (2021) · Canadian Respiratory Journal · doi:10.1155/2021/5434315 · Cited by 10 · see citing works
Timing of routine vaccinations and the risk of childhood asthma
Spycher, B. D., Silverman, M. A., & Kuehni, C. E. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.06.037 · Cited by 10 · see citing works
Vaccines do not cause atopic dermatitis: A systematic review and meta-analysis
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Whole-cell pertussis vaccine in early infancy for the prevention of allergy in children
Chacón, G. P., Ramsay, J. A., Brennan‐Jones, C. G., Estcourt, M. J., Richmond, P., Holt, P. G., & Snelling, T. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013682.pub2 · Cited by 5 · see citing works
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“(10-19) The nine studies vary from large 201 prospective cohort studies to small cross-sectional studies and represent children from 11 202”
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“Recently, most vaccines stimulate the immune system into an allergic reaction [40].”
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The complex link between immunization against childhood diseases and allergy
Kalaboka, S., & Annesi‐Maesano, I. (2007) · Expert Review of Vaccines · doi:10.1586/14760584.6.4.635 · Cited by 6 · see citing works
The Hygiene Hypothesis of Allergy and Asthma
Ege, M. J., & Müller-Rompa, S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.16004-7 · Cited by 6 · see citing works
Khalaj‐Hedayati, A., Chua, C., Smooker, P. M., Moosavi, S., Manta, O. P., Helal, M. H., Ibrahim, M., El-Bahy, Z. M., Supriyanto, G., & Lee, K. W. (2023) · Nanomaterials · doi:10.3390/nano13202796 · Cited by 5 · see citing works
“The server is a binary classifier between allergens and non-allergens and it predicts allergenicity based on the amino acid principle properties such as size, hydrophobicity, helix, and beta-strand formations [73].”
Siddiki, A. Z., Alam, S., Tithi, F. A., Hoque, S. F., Sajib, E. H., Hossen, F. F. B., & Hossain, M. A. (2023) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2023.102706 · Cited by 5 · see citing works
Vaccination status of children in Switzerland
Lang, P. (2007) · edoc (University of Basel) · doi:10.5451/unibas-004420408 · Cited by 5 · see citing works
Mia, M. M., Hasan, M., Hasan, M. M., Khan, S. S., Rahman, M. N., Ahmed, S., Basak, A., Sakib, M. N., & Banik, S. (2021) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2021.105076 · Cited by 4 · see citing works
Supto, M. S. M., Shanto, M. R. H., Tanoy, N. M., Fahim, M. F. A., Hasan, M., Mia, M. M., & Ahmed, S. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110935 · Cited by 3 · see citing works
Siddiki, A. Z., Alam, S., Hossen, F. F. B., & Alim, M. A. (2025) · PLoS ONE · doi:10.1371/journal.pone.0312262 · Cited by 3 · see citing works
Chacón, G. P., Fathima, P., Jones, M., Barnes, R., Richmond, P., Gidding, H. F., Moore, H. C., & Snelling, T. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260388 · Cited by 3 · see citing works
Rahman, M. N., Ahmed, S., Hasan, M., Shuvo, M. S. A., Islam, M. A., Hasan, R., Roy, S., Hossain, H., & Mia, M. M. (2023) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2023.101209 · Cited by 3 · see citing works
VACCINATION AND RISK OF ALLERGIC DISEASE
Hurwitz, E. L., & Morgenstern, H. (2005) · American Journal of Public Health · doi:10.2105/ajph.2004.050583 · Cited by 3 · see citing works
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“In addition to many studies that have found no increased risk of atopies after vaccinations [31-39], there are some works which suggest that a certain risk might be possible.”
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“However, most of the vaccines cause allergic reactions with the help of immunoglobulin E and type 2 T-helper cells [43] .”
Allergies and vaccination: a myth demystified
Ankermann, T., Spindler, T., Gerstlauer, M., & Schmidt, S. M. (2018) · Allergo Journal International · doi:10.1007/s40629-018-0077-8 · Cited by 2 · see citing works
Allergie und Impfen — ein Mythos entmystifiziert
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“However, the results are still controversial as some studies have reported positive association while others could find no association (Kemp et al., 1997; McKeever et al., 2004; Martignon et al., 2005).”
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- Authors
- McKeever, T. M., Lewis, S. A., Smith, C., & Hubbard, R.
- Affiliations
- University of Nottingham (GB)
- Venue
- American Journal of Public Health
- Publisher
- American Public Health Association
- Published
- 2004-06
- Volume
- 94
- Issue
- 6
- Pages
- 985-989
- ISSN
- 0090-0036 (ISSN-L)
- 1541-0048
- PMC
- PMC1448377
- OpenAlex
- W1982817031
- Cited by
- 114
- References
- 29
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 14 · 2020: 13 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Public Health (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- vaccination, allergic diseases, asthma, atopic dermatitis, diphtheria, poliomyelitis, pertussis, tetanus, measles, mumps and rubella, routine childhood immunization, physician visits, birth cohort
- MeSH terms
- Asthma, Child, Child, Preschool, Eczema, England, Female, Humans, Infant, Infant, Newborn, Male, Physicians, Family, Vaccination, Cohort Studies
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