AbstractPrevious research supports a contribution of early-life immune disturbances in the etiology of autism spectrum disorders (ASD). Biomarker studies of the maternal innate (non-adaptive) immune status related to ASD risk have focused on one of the acute phase proteins (APP), C-reactive protein (CRP), with conflicting results. We evaluated levels of eight different APP in maternal serum samples drawn in first trimester, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected

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... , nested within the register-based Stockholm Youth Cohort. Overall, we found no general trend of high levels of maternal APP being associated with increased risk of ASD. In contrast, maternal levels of CRP in the lowest compared to the middle tertile were associated with increased risk of ASD without ID or ADHD in offspring (OR = 2.15, 95 % CI 1.17-3.93). Further, levels of maternal ferritin in the lowest (OR = 1.82, 95 % CI 1.19-2.78) and highest (OR = 1.74, 95 % CI 1.16-2.60) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.58, 95 % CI 1.79-7.17) and highest (OR = 3.20, 95 % CI 1.62-6.29) tertiles of ferritin and risk of ASD with ID. The biological interpretation of lower CRP-levels among mothers to ASD-cases is not clear but might be related to the function of the maternal innate immune system. The finding of aberrant levels of ferritin conferring risk of ASD-phenotypes indicates a plausibly important role of iron during neurodevelopment.