In this proposal, we seek to evaluate common and distinct prenatal risk factors between autism spectrum disorders (ASD) and two other psychiatric disorders, schizophrenia (SZ) and attention deficit hyperactivity disorder (ADHD). We will examine relationships between maternal persistent organic pollutants (POPs) and SZ and ADHD in offspring to provide a basis for comparison for our ongoing study of POPs and ASD. We shall also compare putative associations between low maternal levels of micronutrients (vitamin B12 and vitamin D) and ASD with observed relationships of these exposures in SZ and ADHD. This study will be conducted in the national birth cohort of the Finnish Prenatal Studies (FiPS), the largest seroepidemiologic investigations of prenatal exposures in psychiatric disorders. The study draws upon the Finnish Maternity Cohort (FMC), which consists of over 1.5 million pregnancies in Finland from 1983 to the present. Maternal serum samples were obtained from each gravida during pregnancy, and are archived in one freezer at a single site and the comprehensive national psychiatric registries contain validated diagnoses of ASD, SZ, and ADHD throughout the country. No previous study has ever examined the proposed prenatal factors using maternal biomarkers for these outcomes within a single investigation.
We aim to address these questions in pregnancies of large samples of cases of ASD, these other disorders, and their matched controls, using biomarker assays of these maternal serum samples and large databases on demographic and perinatal factors. The study is based on a nested case-control design. The serum samples will be analyzed for these environmental factors, their occurrence during pregnancy will be compared between the cases and controls, and we shall also compare associations with exposures between disorders to determine if there are common or distinct risk factors. We shall also assess interactive and mediating relationships between risk factors for ASD (including sex and perinatal events), as well as SZ and ADHD. This research has the potential to result in a better understanding of potential risk factors for ASD, and the specificity of putative associations to other psychiatric disorders. Since the risk factors investigated in this study are relatively common in the population, their discovery may lead to prevention of cases of ASD, SZ, and ADHD by straightforward public measures in pregnant women, including reduction of exposure to environmental contaminants, and supplementation with vitamins during pregnancy. This study may also have implications for improving our understanding of pathogenic mechanisms by which prenatal insults alter brain development in ASD and other psychiatric disorders. In summary, the proposed work builds on an existing national birth cohort, and is anticipated to have considerable impact on an emerging and potentially transformative area of research epidemiology and clinical/basic neuroscience, as well as lead to improvements in current public health policy recommendations for care during pregnancy.

Public Health Relevance

This study has significant relevance for public health, as it is aimed at identifying distinct and common prenatal risk factors for autism and other psychiatric disorders (schizophrenia, attention deficit hyperactivity disorder) that have never before been investigated in maternal sera during pregnancy in a single study of a large national birth cohort. This may offer the potential for prevention of autism and these other disorders by straightforward public health measures including reduction of exposure to environmental contaminants and vitamin supplementation. These studies could also result in an improved understanding of how prenatal insults alter brain development in autism and other psychiatric disorders.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Lawler, Cindy P
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Brown, Alan S; Meyer, Urs (2018) Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective. Am J Psychiatry :appiajp201817121311