Early life vitamin D levels and risk of autism spectrum disorders

描述（由申请人提供）：维生素D对神经发育至关重要，维生素D缺乏症患病率的上升已经阻止了自闭症谱系障碍（ASD）的最近增加。大多数维生素D是通过皮肤暴露于UV-B光合成的，其余的来自饮食来源。维生素D缺乏/不足在全球范围内很常见，在冬季、高纬度地区、城市环境和深肤色人群中更为普遍。流行病学证据表明，发育性维生素D缺乏会影响自闭症谱系障碍（ASD）的风险。本项目由来自美国、瑞典和澳大利亚的国际团队领导，他们为支持该项目的基本原理提供了一系列证据：1）动物模型证明怀孕期间维生素D缺乏会干扰神经发育; 2）出生季节性发生在秋季/冬季怀孕的ASD病例过多; 3）瑞典的移民母亲，特别是来自撒哈拉以南非洲的移民母亲，后代患ASD的风险更高; 4）新生儿维生素D缺乏会增加精神分裂症的风险。研究人员提出了一项病例对照研究，测量母亲和儿童的早期维生素D浓度，所有648例ASD病例出生于1998-2000年在瑞典斯德哥尔摩和648例出生日期和性别匹配的对照。具体目标是：目标1：描述ASD病例和对照组产前和新生儿血样中的维生素D状况;目的2：确定产前维生素D浓度与ASD风险的关系;目的3：确定新生儿维生素D浓度与ASD风险的关系。母亲的维生素D是在妊娠前三个月（中位数10.1周）获得的血清中测量的，而新生儿的维生素D是在出生后3-5天采集的血斑中测量的。为了疾病筛查的目的，从瑞典的每一位母亲/儿童身上采集了母亲血清和新生儿干血斑，并存档供卫生研究之用。ASD诊断以前已经过验证。将使用瑞典电子数据登记册中记录的各种协变量数据来解释可能的混杂。使用多个时间点的维生素D测量允许潜在地识别维生素D对ASD风险最重要的病因学窗口，而使用前瞻性收集的生物样品确保结果不是由于反向因果关系（例如，ASD引起的阳光回避行为）。这将是第一项直接测量早期维生素D缺乏是否与ASD风险增加相关的研究。最终，这项研究是重要的，因为母亲/新生儿的维生素D状态是可控的。如果研究证实发育性维生素D缺乏症与自闭症风险之间存在关联，那么它就提出了一级预防的诱人前景，其方式与叶酸补充剂和预防脊柱裂相当。

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.