Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland; INVEST (Inequalities, Interventions and a New Welfare State) Research Flagship, University of Turku, Turku, Finland; Department of Child Psychiatry, Turku University Hospital, Turku, Finland; New York State Psychiatric Institute, Department of Psychiatry, Columbia University Irving Medical Center, New York, New York.
Research Centre for Child Psychiatry, Department of Child Psychiatry, University of Turku, Turku, Finland.
Biol Psychiatry. 2021 Dec 1;90(11):790-797. doi: 10.1016/j.biopsych.2021.07.012. Epub 2021 Jul 21.
Findings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent.
The association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD.
In the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62-0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03-1.79, p = .02) and 20-39 (aOR 1.31, 95% CI 1.01-1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15-1.81, p = .001) and insufficient (30-49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04-1.52, p = .01) compared with sufficient levels.
This finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.
以往关于孕妇 25-羟维生素 D [25(OH)D]水平与后代自闭症谱系障碍（ASD）的研究结果并不一致。
采用全国人群为基础的登记嵌套病例对照研究设计，利用数据来检验孕妇妊娠期间 25(OH)D 水平与后代 ASD 之间的相关性。ASD 病例（n=1558）于 1987 年至 2004 年间出生，2015 年被诊断为 ASD；病例与相同数量的对照相匹配。通过收集孕妇妊娠早期（第 1 和第 2 个三个月）的血清，使用定量免疫分析来测量孕妇妊娠期间的 25(OH)D 水平，并将其储存在芬兰母婴队列的国家生物库中。条件逻辑回归分析了孕妇 25(OH)D 水平与后代 ASD 之间的相关性。
在调整后的模型中，发现 log 转换后的孕妇 25(OH)D 水平升高与后代 ASD 风险降低呈显著相关（调整后的比值比 [aOR] 0.75，95%置信区间 [CI] 0.62-0.92，p=0.005）。按孕妇 25(OH)D 水平的五分位数进行分析，与最高五分位数相比，25(OH)D 水平最低的 2 个五分位数（<20ng/ml，aOR 1.36，95%CI 1.03-1.79，p=0.02）和 20-39ng/ml（aOR 1.31，95%CI 1.01-1.70，p=0.04）患 ASD 的几率增加。与充足水平相比，与维生素 D 缺乏（<30ng/ml，aOR 1.44，95%CI 1.15-1.81，p=0.001）和不足（30-49.9ng/ml，aOR 1.26，95%CI 1.04-1.52，p=0.01）孕妇 25(OH)D 水平相关的 ASD 风险增加。
这一发现对理解孕妇维生素 D 在胎儿大脑发育中的作用以及 ASD 风险增加具有重要意义。
