ASD Tied to Excess Risk for Food Allergy

Norra MacReady

June 08, 2018

A study of nearly 200,000 children in the United States shows a significant association among food, skin, and respiratory allergies and autism spectrum disorder (ASD). The findings support a growing body of evidence for the existence of an immune-mediated subtype of ASD.

The association between ASD and food allergy was particularly strong and robust, indicating that "the gut-brain-behavior axis could be one of the potential mechanisms," the study authors write.

Guifeng Xu, MD, from the Department of Epidemiology in the College of Public Health, University of Iowa, Iowa City, and colleagues published their findings online today in JAMA Network Open.

The results may help explain some of the behaviors displayed by children with ASD, particularly those at the more severe end of the spectrum, who may be unable to describe the pain or discomfort of any gastrointestinal symptoms, Christopher J. McDougle, MD, writes in an accompanying editorial. "[T]heir physical distress may manifest as irritability, aggression, and/or self-injury."

Clinicians should bear this in mind and conduct a thorough history and physical examination to rule out possible medical causes of aberrant behavior in these patients "before proceeding with treatments designed to reduce behavior problems," writes McDougle, from the Lurie Center for Autism, Massachusetts General Hospital, and the Department of Psychiatry, Harvard Medical School, Boston.

In their study, Xu and colleagues used data from the US National Health Interview Survey, an ongoing survey of a nationally representative sample of US civilians that has served as the principal source of information on the health of the population since 1957.

Information for the US National Health Interview Survey is derived through personal interviews conducted in the participants' homes. In households with children 17 years of age or younger, one child is randomly chosen by computer for inclusion, with questions about the child's health answered by a parent or other knowledgeable adult.

For this study, Xu and coauthors included all children between the ages of 3 and 17 years who participated in the US National Health Interview Survey from 1997 to 2016 and for whom information about allergic conditions and ASD was available.

The final sample consisted of 199,520 children, of whom 1868 had ASD (weighted prevalence, 0.95%; 95% confidence interval [CI], 0.89% - 1.01%). The cohort had a mean age of 10.21 years (standard deviation [SD], 4.41 years) and included 102,690 boys (51.47%).

Food allergy was diagnosed in 8734 children, while 24,555 had respiratory allergy and 19,399 had skin allergy. The weighted prevalences were 4.31% (95% CI, 4.20% - 4.43%), 12.15% (95% CI, 11.92% - 12.38%), and 9.91% (95% CI, 9.72% - 10.10%), respectively.

Each of the three allergic conditions were more common among children with ASD than their peers without ASD. Specifically, the weighted prevalence for food allergy was 11.25% among those with ASD vs 4.25% among those without ASD (P < .001); for respiratory allergy, it was 18.73% vs 12.08% (P < .001), and for skin allergy, it was 16.81% vs 9.84% (P < .001).

After adjustment for age, sex, race/ethnicity, family highest education level, family income level, and geographical region, the odds ratio (OR) for ASD was 2.72 (95% CI, 2.26 - 3.28; P < .001) among children with food allergy compared with children who did not have food allergy. Children with respiratory allergy had an OR for ASD of 1.53 (95% CI, 1.32 - 1.78; P < .001) compared with children without respiratory allergy, and among children with skin allergy, the OR for ASD was 1.80 (95% CI, 1.55 - 2.09; P < .001) compared with children free of skin allergy. "The observed associations were modestly attenuated but remained significant after mutual adjustment for other allergic conditions," the authors write.

The association between ASD and food allergy remained significant in all subgroups by age, sex, and race or ethnicity, they add. Respiratory allergy "was not significantly associated with ASD in children aged 3 to 11 years, girls, or white children," and skin allergy "was not significantly associated with ASD in children aged 12 to 17 years or girls."

In addition, the association between respiratory allergy and ASD was stronger for nonwhite than for white children.

The results support previous research showing increased levels of cytokines and immunoglobulins in children with ASD, as well as imbalances in T-cell subsets, the authors write. Together the findings suggest that immunologic disruptions early in life may "influence brain development and social functioning, leading to the development of ASD."

Food allergy, in particular, may lead to neurodevelopmental abnormalities through alterations in the gut microbiome, allergic immune activation, and neuroimmune interactions, which may affect both the enteric and central nervous systems and result in impaired brain function, the authors state.

The findings of this study, added to other research documenting aspects of immune dysfunction in people with ASD and animal models of ASD, suggest that "an immune-mediated subtype of ASD should continue to be pursued and defined," McDougle concludes in the editorial.

Study limitations include use of retrospective and self-reported information regarding the presence of allergies and ASD, lack of information on the onset of the allergies or ASD diagnoses, and no laboratory information on specific immunoglobulin E antibodies for the children's allergic conditions.

The study authors and McDougle have disclosed no relevant financial relationships.

JAMA Network Open. 2018;1(2):e180279.

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