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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Causes of autism spectrum disorders. Epidemiologic studies based on MoBa, the ABC Study and the Autism Database.

Awarded: NOK 4.0 mill.

Autism spectrum disorders (ASDs) have received considerable public attention in recent years,because of large increases in the prevalence of diagnosed cases in most developed countries,and because of speculations that autism may be caused by vaccines or other environmental exposures. However, knowledge about the causes of autism is still limited. It is also unknown whether the higher prevalence reflects a true increase in the occurrence of ASDs, or whether it is merely a result of changing diagnostic practices. In this project we have used the unique resources in the Norwegian mother and child cohort study (MoBa) and the Autism Birth Cohort (ABC) Study nested within MoBa to investigate potential causes for ASD. Our results also include an overview of the prevalence of neurodevelopmental disorders, including ASD, in the Norwegian population. The results from our analyses show that intake of folic acid in early pregnancy reduces the risk of ASD in the child. Furthermore, we have concluded that obesity in the fathers at time of conception is associated with an increased risk of ASD in the child. This association was not found with obesity in the mothers. We have also investigated growth patterns in children with ASD compared to typically developing children through their first year of life, showing that growth in body length is accellerated in boys, but not girls, with ASD, and that head circumference is reduced in girls with ASD compared to typically developing children. We have also been able to reproduce the finding that pregnancy interval below one year increases the risk of ASD in the last born sibling. Results from this project have been extremely important for further research on developmental disorders based on MoBa and the ABC Study. Investigation of other potential causes, including genetics, and infection and inflammation and their potential influence on ASD risk, is currently underway, and more projects are being developed.

The purpose of the project is to study causes of autism spectrum disorders, utilizing the unique opportunities provided by the Norwegian Mother and Child Cohort, the Autism Birth Cohort Study and the Autism Database. Advancing paternal age has consisten tly been demonstrated to increase the risk of autism in children. It is hypothesized that the biological mechanism has to do with de novo genetic and epigenetic events accumulating in the germline as the father becomes older. The proposed project aims to take this research challenge further by combining epidemiologic analyses with studies of de novo mutations in mother-father-child trios in MoBa. DNA for genome-wide analyses will be drawn from the MoBa Biobank (funding for those analyses are obtained thro ugh another grant). The role of folate in the development of ASD will also be elucidated. It has for long been known that a lack of available folate in the mother during pregnancy predisposes the child to neural tube defects and ceft lip and palate. The approach of this project will be to use several measures of folate status, in order to achieve a more precise assessment of maternal folate status and metabolism. A subset of maternal blood samples from the Biobank will undergo extensive analyses of B-vit amin metabolism, and the results will be utilized by this project (funding for those plasma analyses are also obtained through other grants). Lastly, the role of fetal growth retardation will be studied. The evidence of a link between low birth weight, low gestational age and a risk of ASD is inconclusive so far, and there is a need for studies that will allow for a more precise exposure assessment. By using MoBa data, we have data on maternal height and weight, as well as other medical indicators. By u sing those, we can calculate the expected birth weight for any given child, given satisfactory conditions for growth during pregnancy, and thereby obtaining more sophisticated measures of fetal growth.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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