MMR Vaccine Not Linked to Autism, Even in High-Risk Kids

Receipt of the measles, mumps, and rubella (MMR) vaccine was not linked to an increased risk for autism spectrum disorder (ASD), even when older siblings had ASD, a new study shows.

"These findings indicate no harmful association between MMR vaccine receipt and ASD even among children already at higher risk for ASD," Anjali Jain, MD, from the Lewin Group, Falls Church, Virginia, and colleagues write. The researchers present their findings in an article published in the April 21 issue of JAMA.

The investigators used an administrative claims database (the Optum Research Database) connected with a large commercial health plan to conduct a retrospective cohort study. They included children who had been continuously enrolled in the health plan from birth until they were at least aged 5 years during 2001 to 2012. The children also must have had an older sibling who had been continuously enrolled in the health plan for 6 months or longer between 1997 and 2012.

The researchers categorized MMR vaccine exposure according to the number of doses (0, 1, or 2) received between birth and age 5 years.

The study's main outcomes and measures were ASD status, which the researchers defined as two medical claims with a diagnosis code at any point along the autistic disorder or other specified pervasive developmental disorder, including Asperger syndrome, or unspecified pervasive developmental disorder (International Classification of Diseases, Ninth Revision, Clinical Modification, 299.0x, 299.8x, 299.9x).

The researchers included 95,727 children with older siblings. Overall, 994 (1.04%) of those children were diagnosed with ASD and 1929 (2.01%) had an older sibling with ASD. Among the children who had older siblings with ASD, 134 (6.9%) were diagnosed with ASD compared with 860 (0.9%) who were diagnosed with ASD and did not have an affected sibling (P < .001).

The MMR vaccination rate (≥1 dose) for those with siblings without ASD was 84% (n = 78,564) at age 2 years and 92% (n = 86,063) at age 5 years.

MMR vaccination rates were lower for those with older siblings with ASD at age 2 years (73% [n = 1409]) and 5 years (86% [n = 1660]).

The researchers adjusted for potential confounders, including sex of the index child, mother's and father's age at index child's birth, geographic location defined by the four US Census regions, mental health benefits, and index child birth year, which the researchers included to adjust for varying opportunities for ASD to develop or be diagnosed.

Receipt of MMR vaccination was not linked to a higher risk for ASD at any age.

For those with older siblings with ASD, at age 2 years, the adjusted relative risk (RR) for ASD for a single dose of MMR vaccine compared with no vaccine was 0.76 (95% confidence interval [CI], 0.49 - 1.18; P = .22), and at age 5 years, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052).

For those with older siblings without ASD, at age 2 years, the adjusted RR for ASD for a single MMR vaccine dose was 0.91 (95% CI, 0.67 - 1.20; P = .50), and at age 5 years, the adjusted RR for ASD for two vaccine doses was 1.12 (95% CI, 0.78 - 1.59; P = .55).

The cause or causes of autism have been difficult to identify, writes Bryan H. King, MD, MBA, from the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, and Seattle Children's Hospital, Washington, in an accompanying editorial.

"More recently, controversy continues and is reflected in changes in diagnostic criteria and the increasing recognition of heterogeneity that incorporates the word 'spectrum' into the diagnosis," Dr King writes. "With each new prevalence estimate that suggests inexplicable and substantial increases in the number of children diagnosed with the disorder, the urgency to better understand causation is amplified."

Some parents of children with ASD have chosen to put off immunization of later children until they were sure the risk for ASD had passed, Dr King writes.

"Such behavior, which arguably could enrich the immunization rate in the nonautism subgroup relative to the group that may have been showing early atypical development, might create the impression that MMR vaccine is actually reducing risk for ASD. Indeed, Jain et al report relative risks of less than 1.0." Dr King explains. "Even so, short of arguing that MMR vaccine actually reduces the risk of ASD in those who were immunized by age 2 years, the only conclusion that can be drawn from the study is that there is no signal to suggest a relationship between MMR and the development of autism in children with or without a sibling who has autism."

This study was funded by the National Institute of Mental Health, National Institutes of Health, and the US Department of Health and Human Services. Dr Jain and two coauthors report being employees of the Lewin Group. Two coauthors are employees of Optum, which a wholly owned subsidiary of UnitedHealth Group. The Lewin Group is an Optum company. The Lewin Group operates with editorial independence. The other authors and Dr King have disclosed no relevant financial relationships.

JAMA. 2015;313:1518-1519, 1534-1540.