Early life vitamin D levels and risk of autism spectrum disorders

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Vitamin D is critical for neurodevelopment, and a rise in prevalence of vitamin D deficiency has paralleled the recent increase in autism spectrum disorders (ASD). Most vitamin D is synthesized through skin exposure to UV-B light with the rest derived from dietary sources. Vitamin D deficiency/insufficiency is common globally, and more prevalent in winter, in high latitudes, urban settings and in dark-skinned individuals. Epidemiological evidence suggests that developmental vitamin D deficiency influences risk of autism spectrum disorders (ASD). The present project is led by an international team from the United States, Sweden, and Australia that has contributed to lines of evidence supporting the project rationale: 1) Animal models demonstrate vitamin D deficiency during pregnancy interferes with neurodevelopment; 2) Birth seasonality occurs with excess ASD cases conceived in fall/winter; 3) Immigrant mothers in Sweden, especially from sub-Saharan Africa, have higher risk of offspring ASD; 4) Neonatal vitamin D deficiency increases risk of schizophrenia. The investigators propose a case-control study measuring early life vitamin D concentrations in both mother and child, for all 648 ASD cases born in 1998-2000 in Stockholm, Sweden and 648 birthdate and sex-matched controls. The specific aims are to: Aim 1: Describe vitamin D status in prenatal and neonatal blood samples in ASD cases and controls; Aim 2: Determine the associations of prenatal vitamin D concentrations and risk of ASD; Aim 3: Determine the associations of neonatal vitamin D concentrations and risk of ASD. Vitamin D in the mother is measured in serum obtained in the first trimester (median 10.1 weeks), while vitamin D in the neonate is measured in blood spots taken 3-5 days after birth. Both maternal serum and neonatal dried blood spots are obtained from every mother/child in Sweden for the purposes of disease screening and archived for health research use. ASD diagnoses have been previously validated. A wide array of covariate data documented in Sweden's electronic data registers will be used to account for possible confounding. The use of multiple timepoints of vitamin D measurements allows for the potential identification of an etiological window for which vitamin D is most important to ASD risk, while the use of prospectively collected biosamples assures that results are not due to reverse causality (e.g., ASD causing sun avoidance behavior). This will be the first study directly measuring whether early life vitamin D deficiency is associated with increased risk of ASD. Ultimately, the proposed research is significant because maternal/neonatal vitamin D status is controllable. If studies confirm the association between developmental vitamin D deficiency and risk of autism, then it raises the tantalizing prospect of primary prevention, in a manner comparable to folate supplementation and the prevention of spina bifida.