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

全国出生队列中自闭症和其他精神病结果的产前因素

• 批准号: 10005353
• 负责人: Alan Stewart Brown
• 金额: $ 45.38万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005353
• 关键词: Address; Apgar Score; Archives; Area; Attention Deficit Disorder; Attention deficit hyperactivity disorder; Behavioral; Biological Assay; Biological Markers; Birth; Brain; Caring; Child Development; Child Health; Childhood; Clinical; Cognitive; Country; Databases; Development; Diagnosis; Disease; Environmental Pollution; Environmental Risk Factor; Event; Exposure to; Finland; Folic Acid; Freezing; Functional disorder; Genetic; Genetic Risk; Gestational Age; Health Policy; Homocysteine; Investigation; Lead; Maternal Exposure; Measures; Mediating; Mental disorders; Micronutrients; Neonatal; Neurosciences; Nutrient; Outcome; Parents; Pathogenesis; Pathogenicity; Perinatal; Play; Polychlorinated Biphenyls; Population; Pregnancy; Pregnant Women; Prevention; Prevention strategy; Process; Public Health; Recommendation; Registries; Research; Research Design; Risk; Risk Factors; Role; Sample Size; Sampling; Schizophrenia; Serum; Siblings; Site; Specificity; Suggestion; Supplementation; Symptoms; Twin Studies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin D; Vitamins; Weight; Work; autism spectrum disorder; base; case control; cohort; comorbidity; design; epidemiology study; improved; maternal serum; neuropsychiatric disorder; offspring; persistent organic pollutants; prenatal; prenatal exposure; prenatal risk factor; proband; public health relevance; sex; virtual

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.

在本提案中，我们寻求评估自闭症谱系之间常见和独特的产前危险因素 障碍（ASD）和其他两种精神疾病，精神分裂症（SZ）和注意力缺陷多动症 障碍（多动症）。我们将研究母体持久性有机污染物 (POP) 与 后代中的 SZ 和 ADHD 为我们正在进行的 POP 和 ASD 研究提供比较基础。我们 还应比较母体微量营养素（维生素 B12 和维生素 B12）水平低之间的假定关联。 维生素 D）和 ASD，并观察到这些暴露与 SZ 和 ADHD 的关系。这项研究将 在芬兰产前研究 (FiPS) 的全国出生队列中进行，该研究是最大的血清流行病学研究 对精神疾病产前暴露的调查。该研究借鉴了芬兰产妇 队列 (FMC)，由 1983 年至今芬兰超过 150 万例妊娠组成。产妇 血清样本是在怀孕期间从每个孕妇身上采集的，并保存在一个冰箱中。 网站和综合国家精神病学登记处包含 ASD、SZ 和 ADHD 的经过验证的诊断 全国各地。之前没有研究使用母亲来检验所提出的产前因素 在一次调查中确定这些结果的生物标志物。我们的目标是解决这些问题 使用自闭症谱系障碍（ASD）、这些其他疾病及其匹配对照的大样本怀孕 对这些母体血清样本和人口统计和围产期大型数据库进行生物标志物测定 因素。该研究基于嵌套病例对照设计。将分析血清样本中的这些内容 环境因素，它们在怀孕期间的发生将在病例和对照之间进行比较， 我们还将比较疾病之间的暴露关联，以确定是否存在共同点 或不同的风险因素。我们还应评估风险因素之间的交互和中介关系 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 更好地了解自闭症谱系障碍的潜在风险因素，以及与其他因素的假定关联的特殊性 精神疾病。由于本研究调查的危险因素在人群中相对常见， 他们的发现可能会导致通过直接的公共措施来预防 ASD、SZ 和 ADHD 病例 孕妇，包括减少与环境污染物的接触，以及补充 怀孕期间的维生素。这项研究也可能对提高我们的理解有影响 产前侮辱改变自闭症谱系障碍和其他精神病患者大脑发育的致病机制 失调。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 对流行病学研究的新兴和潜在变革领域产生相当大的影响 临床/基础神经科学，以及导致当前公共卫生政策建议的改进 用于怀孕期间的护理。