Background:
The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake.
Objective:
To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination.
Design:
Nationwide cohort study.
Setting:
Denmark.
Participants:
657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013.
Measurements:
Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score).
Results:
During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100 000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination.
Limitation:
No individual medical charts were reviewed.
Conclusion:
The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases.
Primary Funding Source:
Novo Nordisk Foundation and Danish Ministry of Health.
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Author, Article and Disclosure Information
Financial Support: By the Novo Nordisk Foundation and the Danish Ministry of Health.
Disclosures: Dr. Hviid reports grants from Novo Nordisk Foundation during the conduct of the study. Dr. Hansen reports grants from Novo Nordisk Foundation during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2101.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol, statistical code, and data set: Not available.
Corresponding Author: Anders Hviid, DrMedSci, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark; e-mail, [email protected].
Current Author Addresses: Drs. Hviid, Hansen, Frisch, and Melbye: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
Author Contributions: Conception and design: A. Hviid, M. Melbye, J. Vinsløv Hansen.
Analysis and interpretation of the data: A. Hviid, M. Melbye, J. Vinsløv Hansen.
Drafting of the article: A. Hviid.
Critical revision for important intellectual content: M. Frisch, M. Melbye, J. Vinsløv Hansen.
Final approval of the article: M. Frisch, A. Hviid, M. Melbye, J. Vinsløv Hansen.
Provision of study materials or patients: M. Frisch.
Statistical expertise: J. Vinsløv Hansen.
Obtaining of funding: A. Hviid.
Administrative, technical, or logistic support: M. Frisch, M. Melbye.
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