Olga Egorova1, Robin Myte2, Jörn Schneede3, Bruno Hägglöf4, Sven Bölte5,6,7, Erik Domellöf8, Barbro Ivars A'roch4, Fredrik Elgh9, Per Magne Ueland10,11, Sven-Arne Silfverdal1. 1. 1Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden. 2. 2Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. 3. 3Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden. 4. 4Department of Child and Adolescent Psychiatry, Umea University, Umeå, Sweden. 5. Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Stockholm, Sweden. 6. 6Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden. 7. 7Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA Australia. 8. 8Department of Psychology, Umeå University, Umeå, Sweden. 9. 9Department of Clinical Microbiology, Umeå University, Umeå, Sweden. 10. 10Bevital AS, Department of Clinical Science, University of Bergen, Bergen, Norway. 11. 11Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Abstract
Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
Authors: Steinar Hustad; Simone Eussen; Øivind Midttun; Arve Ulvik; Puck M van de Kant; Lars Mørkrid; Randi Gislefoss; Per M Ueland Journal: Clin Chem Date: 2011-12-22 Impact factor: 8.327