Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring.
We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD.
Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.
Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.
To the Editor.
The study by Atladottir and colleagues found that influenza infection during pregnancy had a significant association with increased risk of infantile autism.1 No explanation was given to explain this finding. We would like to propose that vitamin D deficiency during pregnancy might explain the findings.
The vitamin D-autism hypothesis was proposed by Cannell in 2008.2 Cannell and colleagues also proposed that vitamin D deficiency was an important risk factor for influenza in 2006.3 Since A (autism) is associated with B (influenza), it may be a third factor, C (vitamin D deficiency), explains the findings of Atlad?ttir and colleagues.
Assuming that the vitamin D-influenza and vitamin D-autism hypotheses are correct, what health policy recommendations can be made? We propose that pregnant women have their serum 25-hydroxyvitamin D concentration measured and then take supplements or increase their ultraviolet-B irradiance to raise the concentration to above 30-40 ng/ml (75-100 nmol/l). These values are supported by studies of adverse pregnancy outcomes in general4 and infant neuropsychological development in particular.5
References 1.Atladottir HO, Henriksen TB, Schendel DE, Parner ET. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. 2012;133(6):1-5 epub 2. Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-759. 3. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129-1140. 4. Wagner CL, Taylor SN, Dawodu A, Johnson DD, Hollis BW. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients. 2012;4(3):208-230. 5. Morales E, Guxens M, Llop S, et al. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics. 2012;130(4):e913-e920.
Conflict of Interest:
Funding source: No funding was provided for preparation of this manuscript. Financial Disclosure WBG receives funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), the Vitamin D Society (Canada), and the Sunlight Research Forum (Veldhoven). JJC is president of the Vitamin D Council and receives remuneration from Purity Products, Inc. Conflict of Interest: The authors have no conflict of interest to disclose.