Prenatal Factors in Autism and other Psychiatric Outcomes in a National Birth Cohort

在这项建议中，我们试图评估自闭症谱系之间共同的和不同的产前危险因素。 精神障碍(ASD)和另外两种精神障碍，精神分裂症(SZ)和注意缺陷多动 精神障碍(ADHD)。我们将研究母体持久性有机污染物(POP)和 SZ和ADHD在后代中的分布，为我们正在进行的POPS和ASD的研究提供一个比较的基础。我们 还应比较孕妇体内微量营养素(维生素B12和维生素B12)水平较低之间的假定联系 维生素D)和ASD与SZ和ADHD中这些暴露的观察到的关系。这项研究将是 在芬兰产前研究(FIPS)的全国出生队列中进行，这是最大的血清流行病学 精神疾病的产前暴露调查。这项研究借鉴了芬兰的母性 队列(FMC)，从1983年到现在，芬兰有超过150万例怀孕。母性 在怀孕期间从每个孕妇身上获取血清样本，并将其保存在一个冷冻箱中。 网站和全面的国家精神病学登记包含ASD、SZ和ADHD的有效诊断 在全国范围内。在此之前，还没有一项研究用母体因素来检验所提出的产前因素。 这些结果的生物标记物在一次调查中。我们的目标是在以下方面解决这些问题 对ASD、这些其他疾病的大样本病例及其匹配对照的妊娠情况，使用 这些母体血清样本和人口学及围产期大型数据库的生物标志物分析 各种因素。本研究基于嵌套式病例对照设计。将对这些血清样本进行分析 环境因素，它们在怀孕期间的发生情况将在病例组和对照组之间进行比较， 我们还将比较疾病之间暴露的联系，以确定是否有共同的 或不同的风险因素。我们还将评估风险因素之间的交互和中介关系，以 ASD(包括性行为和围产期事件)，以及SZ和ADHD。这项研究有可能导致 更好地了解ASD的潜在危险因素，以及假定与其他疾病相关的特异性 精神障碍。由于本研究调查的危险因素在人群中相对常见， 他们的发现可能导致通过直接的公共措施来预防ASD、SZ和ADHD病例 孕妇，包括减少暴露在环境污染物中，并补充 怀孕期间的维生素。这项研究也可能对提高我们对 产前侮辱改变自闭症和其他精神病患者大脑发育的致病机制 精神错乱。总之，拟议的工作建立在现有的全国出生队列的基础上，预计将 对一个新兴的和潜在的变革性流行病学研究领域产生相当大的影响 临床/基础神经科学，以及导致改进当前的公共卫生政策建议 用于怀孕期间的护理。

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.