Association between estimated cumulative vaccine antigen exposure through the first 23 months of life and non-vaccine-targeted infections from 24 through 47 months of age.
Open accessAbstract
Importance: Some parents are concerned that multiple vaccines in early childhood could weaken their child's immune system. Biological data suggest that increased vaccine antigen exposure could increase the risk for infections not targeted by vaccines. Objective: To examine estimated cumulative vaccine antigen exposure through the first 23 months of life in children with and without non-vaccine-targeted infections from 24 through 47 months of age. Design, Setting, and Participants: A nested case-control study was conducted in 6 US health care organizations participating in the Vaccine Safety Datalink. Cases were identified by International Classification of Diseases codes for infectious diseases in the emergency department and inpatient medical settings and then validated by medical record review. Cases of non-vaccine-targeted infection were matched to controls by age, sex, health care organization site, and chronic disease status. Participants were children ages 24 through 47 months, born between January 1, 2003, and September 31, 2013, followed up until December 31, 2015. Exposures: Cumulative vaccine antigen exposure, estimated by summing the number of antigens in each vaccine dose received from birth through age 23 months. Main Outcomes and Measures: Non-vaccine-targeted infections, including upper and lower respiratory infections and gastrointestinal infections, from 24 through 47 months of age, and the association between these infections and estimated cumulative vaccine exposure from birth through 23 months. Conditional logistic regression was used to estimate matched odds ratios representing the odds of non-vaccine-targeted infections for every 30-unit increase in estimated cumulative number of antigens received. Results: Among the 944 patients (193 cases and 751 controls), the mean (SD) age was 32.5 (6.3) months, 422 (45%) were female, and 61 (7%) had a complex chronic condition. Through the first 23 months, the estimated mean (SD) cumulative vaccine antigen exposure was 240.6 (48.3) for cases and 242.9 (51.1) for controls. The between-group difference for estimated cumulative antigen exposure was -2.3 (95% CI, -10.1 to 5.4; P = .55). Among children with vs without non-vaccine-targeted infections from 24 through 47 months of age, the matched odds ratio for estimated cumulative antigen exposure through age 23 months was not significant (matched odds ratio, 0.94; 95% CI, 0.84 to 1.07). Conclusions and Relevance: Among children from 24 through 47 months of age with emergency department and inpatient visits for infectious diseases not targeted by vaccines, compared with children without such visits, there was no significant difference in estimated cumulative vaccine antigen exposure through the first 23 months of life.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Epidemiologic and immunologic data refute the concept that vaccines dampen the immune response.
“Epidemiologic and immunologic data refute the concept that vaccines dampen the immune response.”
From Vaccine Safety: Myths and Misinformation (2020) · cites this paper as Glanz et al., 2018
The Discussion reports no significant association between estimated vaccine antigen exposure and non-vaccine-targeted infections in the children studied, supporting a narrower epidemiologic point. It does not show that epidemiologic and immunologic data refute immune dampening generally: the Discussion says proposed immunologic mechanisms remain unestablished and that responses can be beneficial or detrimental. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA nested case-control study of 944 patients from 6 US healthcare organizations found no differences in cumulative vaccine antigen exposure in the first 24 months of life between children admitted to hospital with a non-vaccine-targeted infection and those who were not.
“A second nested case control study included 944 patients from 6 United States healthcare organizations to examine cumulative vaccine antigen exposure in the first 24 months of life and risk of non-vaccine-targeted infections from 24–47 months. The group found no differences in cumulative vaccine antigen exposure between children who were admitted to hospital with a non-vaccine targeted infection”
From Vaccine Safety: Myths and Misinformation (2020) · cites this paper as Glanz et al., 2018
Looking at children who presented to the emergency department with infections not included in the vaccine programme, there was no difference in terms of their previous antigen exposure by vaccination.
“Looking at children who presented to the emergency department with infections not included in the vaccine programme, there was no difference in terms of their previous antigen exposure by vaccination96.”
From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [96]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1990) · Choice Reviews Online · doi:10.5860/choice.27-3338 · Cited by 35,305 · see citing works
Fiore, A. E., Shay, D. K., Broder, K., Iskander, J. K., Uyeki, T. M., Mootrey, G., Bresee, J. S., & Cox, N. S. (2001) · PsycEXTRA Dataset · doi:10.1037/e548312006-001 · Cited by 5,006 · see citing works
Logistic Regression Using SAS: Theory and Application
Allison, P. D. (1999) · Cited by 2,860 · see citing works
(2002) · PsycEXTRA Dataset · doi:10.1037/e548512006-001 · Cited by 1,713 · see citing works
Fiore, A. E., Wasley, A., & Bell, B. P. (1999) · PsycEXTRA Dataset · doi:10.1037/e547812006-001 · Cited by 1,130 · see citing works
Parashar, U. D., Alexander, J. P., & Glass, R. I. (2006) · PsycEXTRA Dataset · doi:10.1037/e531952006-001 · Cited by 675 · see citing works
Roush, S. W. (2007) · JAMA · doi:10.1001/jama.298.18.2155 · Cited by 633 · see citing works
Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review
Higgins, J. P. T., Soares‐Weiser, K., López-López, J. A., Κακούρου, Α., Chaplin, K., Christensen, H., Martin, N. K., Sterne, J. A. C., & Reingold, A. L. (2016) · BMJ · doi:10.1136/bmj.i5170 · Cited by 629 · see citing works
(2009) · doi:10.1007/978-0-387-87959-8 · Cited by 554 · see citing works
Pediatric Medical Complexity Algorithm: A New Method to Stratify Children by Medical Complexity
Simon, T. D., Cawthon, M. L., Stanford, S., Popalisky, J., Lyons, D., Woodcox, P., Hood, M., Chen, A. Y., & Mangione-Smith, R. M. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3875 · Cited by 462 · see citing works
Nuorti, J. P., & Whitney, C. G. (2010) · PubMed · Cited by 421 · see citing works
Applying Quantitative Bias Analysis to Epidemiologic Data
Fink, A. K., Fox, M. P., & Lash, T. L. (2009) · Statistics in the health sciences · doi:10.1007/b97920 · Cited by 354 · see citing works
The Vaccine Safety Datalink: A Model for Monitoring Immunization Safety
Baggs, J. M., Gee, J. M., Lewis, E. M., Fowler, G. L., Benson, P. J., Lieu, T. A., Naleway, A. L., Klein, N. P., Baxter, R. P., Belongia, E. A., et al. (2011) · PEDIATRICS · doi:10.1542/peds.2010-1722h · Cited by 349 · see citing works
Self-citationAddressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant's immune system?
Offit, P. A., Quarles, J., Gerber, M. A., Hackett, C. J., Marcuse, E. K., Kollman, T. R., Gellin, B. G., & Landry, S. (2002) · Pediatrics · doi:10.1542/peds.109.1.124 · Cited by 312 · see citing works
Heterologous immunity between viruses
Welsh, R. M., Che, J. W., Brehm, M. A., & Selin, L. K. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2010.00897.x · Cited by 294 · see citing works
Kennedy, A., Basket, M. M., & Sheedy, K. (2011) · PEDIATRICS · doi:10.1542/peds.2010-1722n · Cited by 280 · see citing works
Benefits from immunization during the vaccines for children program era - United States, 1994-2013.
Whitney, C. G., Zhou, F., Singleton, J. A., & Schuchat, A. (2014) · PubMed Central · Cited by 236 · see citing works
Alternative Vaccination Schedule Preferences Among Parents of Young Children
Dempsey, A. F., Schaffer, S. E., Singer, D., Butchart, A. T., Davis, M. M., & Freed, G. L. (2011) · PEDIATRICS · doi:10.1542/peds.2011-0400 · Cited by 229 · see citing works
Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines
Blok, B. A., Arts, R. J. W., van Crevel, R., Benn, C. S., & Netea, M. G. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.5ri0315-096r · Cited by 211 · see citing works
Geographic Clusters in Underimmunization and Vaccine Refusal
Lieu, T. A., Ray, G. T., Klein, N. P., Chung, C., & Kulldorff, M. (2015) · PEDIATRICS · doi:10.1542/peds.2014-2715 · Cited by 195 · see citing works
A Mixed Methods Study of Parental Vaccine Decision Making and Parent–Provider Trust
Glanz, J. M., Wagner, N. M., Narwaney, K. J., Shoup, J. A., McClure, D. L., McCormick, E. V., & Daley, M. F. (2013) · Academic Pediatrics · doi:10.1016/j.acap.2013.05.030 · Cited by 187 · see citing works
Self-citationSørup, S., Benn, C. S., Poulsen, A., Krause, T. G., Aaby, P., & Ravn, H. (2014) · JAMA · doi:10.1001/jama.2014.470 · Cited by 181 · see citing works
Frequency of Alternative Immunization Schedule Use in a Metropolitan Area
Robison, S. G., Groom, H. C., & Young, C. M. (2012) · PEDIATRICS · doi:10.1542/peds.2011-3154 · Cited by 98 · see citing works
Self-citationNon-specific immunological effects of selected routine childhood immunisations: systematic review
Kandasamy, R., Voysey, M., McQuaid, F., de Nie, K., Ryan, R., Orr, O. E., Uhlig, U., Sande, C., O’Connor, D., & Pollard, A. J. (2016) · BMJ · doi:10.1136/bmj.i5225 · Cited by 96 · see citing works
Hinshaw, A. S. (2013) · Cited by 79 · see citing works
Bardenheier, B. H., McNeil, M. M., Wodi, A. P., McNicholl, J. M., & Destefano, F. R. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix442 · Cited by 52 · see citing works
Self-citationVaccination and heterologous immunity: educating the immune system
Gil, A., Kenney, L. L., Mishra, R., Watkin, L. B., Aslan, N., & Selin, L. K. (2015) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1093/trstmh/tru198 · Cited by 47 · see citing works
Institute of Medicine (2002) · National Academies Press eBooks · doi:10.17226/10306 · Cited by 37 · see citing works
Sankoh, O. A., Welaga, P., Debpuur, C. Y., Zandoh, C., Gyaase, S., Poma, M. A., Mutua, M. K., Hanifi, S. M. A., Martins, C. L., Nebie, E. I., et al. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyu101 · Cited by 35 · see citing works
Frew, P. M., Fisher, A. K., Basket, M. M., Chung, Y., Schamel, J. T., Weiner, J. L., Mullen, J. N., Omer, S. B., & Orenstein, W. A. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.08.001 · Cited by 34 · see citing works
Childhood vaccination and nontargeted infectious disease hospitalization.
Hviid, A. (2005) · JAMA · doi:10.1001/jama.294.6.699 · Cited by 31 · see citing works
Immunization Safety Review: Multiple Immunizations and Immune Dysfunction
Prevention, D. (2020) · Cited by 29 · see citing works
Number of antigens in early childhood vaccines and neuropsychological outcomes at age 7-10 years.
Iqbal, S., Barile, J. P., Thompson, W. W., & DeStefano, F. (2013) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.3482 · Cited by 23 · see citing works
Self-citationDaley, M. F., Glanz, J. M., Newcomer, S. R., et al. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.02.058 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [12]12. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.
- [15]15. Plotkin SA, Orenstein W, Offit PA, Edwards KM. Vaccines. 7th ed. Philadelphia, PA: Saunders; 2017.
Cited by
Sorted by citations
A guide to vaccinology: from basic principles to new developments
Pollard, A. J., & Bijker, E. M. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00479-7 · Cited by 1,593 · see citing works
Vaccine Safety: Myths and Misinformation
Geoghegan, S., O’Callaghan, K. P., & Offit, P. A. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00372 · Cited by 275 · see citing works
“However, in a later analysis that included the 2010– 2011 season and adjusted for antecedent respiratory infection there was no increased risk following 1.27 million 2009- 10 MIV or 2.8 million 2010-11 TIV doses (Greene et al., 2013).”
BackgroundInfluentialPrincipal Controversies in Vaccine Safety in the United States
DeStefano, F., Bodenstab, H. M., & Offit, P. A. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz135 · Cited by 86 · see citing works
Self-citation
- Authors
- Glanz, J. M., Newcomer, S. R., Daley, M. F., DeStefano, F., Groom, H. C., Jackson, M. L., Lewin, B. J., McCarthy, N. L., McClure, D. L., Narwaney, K. J., Nordin, J. D., & Zerbo, O.
- Affiliations
- Kaiser Permanente (US)
- Centers for Disease Control and Prevention (US)
- Kaiser Permanente Center for Health Research (US)
- Kaiser Permanente Washington Health Research Institute (US)
- Marshfield Clinic Research Foundation (US)
- HealthPartners (US)
- Corresponding author
- Glanz, Jason M.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2018-03-06
- Volume
- 319
- Issue
- 9
- Pages
- 906
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5885913
- OpenAlex
- W2792847349
- Cited by
- 54
- References
- 35
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 7
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Social Sciences › Health › Vaccine Coverage and Hesitancy
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- vaccine safety, early childhood vaccination, respiratory infections, gastrointestinal infections, upper respiratory tract infection, lower respiratory tract infection, Vaccine Safety Datalink, emergency department visits, chronic disease
- MeSH terms
- Antigens, Child, Preschool, Croup, Female, Gastrointestinal Diseases, Humans, Immunization Schedule, Infant, Infections, Male, Otitis Media, Respiratory Tract Infections, Vaccines, Case-Control Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
