Prenatal factors and risk of autism in a Finnish national birth cohort

描述(由申请人提供)：在这项提案中，我们将调查怀孕期间的环境因素是否与子女被诊断为自闭症的可能性有关。这些因素包括感染、免疫异常、荷尔蒙和吸烟。我们的目标是在1,000名自闭症病例和1,000名健康儿童的怀孕中解决这些问题，使用从1987-2007年间几乎所有芬兰怀孕时提取和存储的母体血清样本。与芬兰的性别、出生日期、出生地和居住地相匹配的自闭症儿童和健康儿童将从详细的国家数据库中识别出来，这些数据库包含了芬兰几乎所有自闭症病例的诊断。自闭症患者母亲和健康对照母亲的血清样本将被分析这些环境因素。我们还将测试怀孕期间的这些母亲环境因素是否与其他妊娠和分娩并发症有关，以及是否与自闭症发病前几年儿童头部发育异常有关。在之前的研究中，已经观察到自闭症儿童头部尺寸的增加，这也可能与疾病的发展有关。为此，我们将利用芬兰几乎所有新生儿的其他大型国家数据库。此外，我们将测试患有自闭症的男孩和女孩对这些环境因素的易感性是否存在差异。这项研究将为未来的项目奠定基础，在这些项目中，我们将进一步扩大样本规模，达到多达5,000例自闭症病例，扩大所研究的风险因素类型和婴儿/儿童发展指标，比较不同自闭症亚型之间风险因素的影响，并评估基因与环境的相互作用。这项研究有可能导致更好地理解自闭症的不同原因和可能导致疾病的不同发育途径。这些原因的发现可以通过改进产前护理来预防自闭症病例，并有助于确定哪些儿童有患自闭症的风险。 公共卫生相关性：这项工作具有很高的公共卫生意义。查明自闭症的产前病因及其与其他发育先天因素的关系，有可能通过可执行的公共卫生措施，如接种流感疫苗、预防性传播疾病、补充甲状腺激素和针对孕妇的禁烟运动，消除相当一部分自闭症病例。此外，这项建议中描述的研究有可能有助于确定自闭症风险儿童，以及这些早期生活暴露导致这种疾病风险增加的致病机制，这可能导致新的预防和治疗干预模式。

DESCRIPTION (provided by applicant): In this proposal, we will investigate whether environmental factors during pregnancy are related to the likelihood that the offspring will be diagnosed with autism. These factors include infections, immune abnormalities, hormones, and smoking. We aim to address these questions in pregnancies of 1,000 autism cases and 1,000 healthy children using maternal serum samples that were drawn and stored in nearly all pregnancies in Finland from 1987-2007. Children with autism and healthy children matched to the cases on sex, date of birth, birth place and residence in Finland will be identified from detailed national databases that contain diagnoses on nearly all cases of autism in Finland. The serum samples of mothers of autism cases and mothers of healthy controls will be analyzed for these environmental factors. We shall also test whether these maternal environmental factors during pregnancy are related to other pregnancy and birth complications and to abnormalities in growth of the child's head over the first few years of life, prior to the onset of autism. In previous studies, increased head size has been observed in children with autism and this may also be related to development of the illness. For this purpose, we will make use of other large national databases available in nearly all births in Finland. Moreover, we will test whether there are differences in susceptibility to these environmental factors between boys and girls with autism. This study will lay the groundwork for future projects in which we will increase the sample size further, to as many as 5,000 cases of autism, expand the types of risk factors and infant/childhood developmental measures examined, compare effects of risk factors between different subtypes of autism, and assess gene-environment interactions. This research has the potential to result in a better understanding of the different causes of autism and different developmental pathways that can lead to the illness. The discovery of these causes can lead to prevention of cases of autism by improved prenatal care and to the identification of children who are at risk of developing autism. PUBLIC HEALTH RELEVANCE: This work has high public health significance. The identification of prenatal etiologies of autism, and their relationship with other developmental antecedents, has the potential to lead to the eradication of a considerable portion of autism cases through implementable public health measures, such as the administration of influenza vaccination, the prevention of sexually transmitted diseases, thyroid hormone supplementation, and anti-smoking campaigns targeted to pregnant women. Moreover, the research described in this proposal has the potential to facilitate the identification of children at risk for autism and to pathogenic mechanisms by which these early life exposures operate to increase risk for this disorder, which can lead to new modalities of prevention and therapeutic intervention.