Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Abstract

ObjectiveIndividuals diagnosed with autism spectrum disorders (ASD) are reported to have higher levels of antibodies directed towards gliadin, a component of wheat gluten. However, no study has examined such antibodies in etiologically-relevant periods before diagnosis. The objective of this study is to investigate if maternal levels of immunoglobulin G antibodies directed at gliadin, during pregnancy and at the time of birth, are associated with ASD in offspring. MethodsIn this population-based study set in Sweden with 921 ASD cases and 1090 controls, we analyzed levels of anti-gliadin antibodies (AGA) in archived neonatal dried blood spots (NDBS, as maternal IgG is transferred to the fetus) and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations to any ASD diagnosis and considering common comorbidities (i.e. intellectual disability [ID] and attention-deficit/hyperactivity disorder [ADHD]). We compared 206 ASD cases to their unaffected siblings to examine the potential for confounding by shared familial factors. ResultsHigh levels ([≥]90th percentile) of maternal AGA were associated with decreased odds of ASD, particularly ASD with comorbid ID, when measured in NDBS (OR 0.51, 95% CI 0.30-0.87) with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of maternal AGA were similarly associated with lower odds of ASD with ID in the sibling comparison. ConclusionsThis first study of exposure to AGA in the pre- and perinatal periods suggests that high levels of maternal AGA are associated with lower odds of ASD with ID.