Anna Suleri , Tonya White , Lot de Witte , Frederieke Gigase , Charlotte A.M. Cecil , Vincent W.V. Jaddoe , Michael Breen , Manon H.J. Hillegers , Ryan L. Muetzel , Veerle Bergink
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引用次数: 0
Abstract
Background
Maternal immune activation (MIA) has been hypothesized to have an adverse effect on child neurodevelopment, but only a few neuroimaging studies have been performed to date, mostly in neonates. In this population-based cohort study, we investigated the association between MIA and multiple neuroimaging modalities depicting brain development from childhood to adolescence.
Methods
We used data of mother-child pairs from the Generation R Study. To define our exposure, we measured interleukin (IL) 1β, IL-6, IL-17a, IL-23, interferon gamma, and C-reactive protein at 2 time points during pregnancy. Because levels of these 5 cytokines were highly correlated, we were able to compute a cytokine index. We used multiple brain imaging modalities as outcomes, including global and regional measures of brain morphology (structural magnetic resonance imaging, volume; n = 3295), white matter microstructure (diffusion magnetic resonance imaging, fractional anisotropy and mean diffusivity; n = 3267), and functional connectivity (functional magnetic resonance imaging, graph theory measures, and network-level connectivity; n = 2914) in the children at ages 10 and 14 years. We performed mixed effects models using child’s age as a continuous time variable.
Results
We found no significant effect of time on any neuroimaging outcomes in children over time, and there was no time × MIA interaction. These associations were similar for the cytokine index, C-reactive protein, and individual cytokines. We observed no evidence for differential effects of timing of prenatal MIA or child sex after multiple testing correction.
Conclusions
In this longitudinal population-based study, we found no evidence for an association between MIA and child brain development in the general population. Our findings differ from previous research in neonates that have shown structural and functional brain abnormalities after MIA.
背景：母体免疫激活（MIA）被认为会对儿童的神经发育产生不良影响，但迄今为止仅开展了少数几项神经影像学研究，其中大部分是针对新生儿的。在这项基于人群的队列研究中，我们调查了 MIA 与描述儿童至青少年时期大脑发育的多种神经影像模式之间的关联：我们使用了 R 世代研究中的母子对数据。为了确定我们的暴露，我们在怀孕期间的两个时间点测量了IL-1β、IL-6、IL-17a、IL-23和IFN-γ以及CRP。鉴于这五种细胞因子的水平高度相关，我们可以计算出细胞因子指数。我们使用了多种脑成像模式作为研究结果，包括在儿童平均 10 岁和 14 岁时对大脑形态（结构磁共振成像，体积，n=3,295）、白质微结构（扩散磁共振成像，FA 和 MD，n=3,267）和功能连接（功能磁共振成像，图论测量和网络级连接，n=2,914）的整体和区域测量。我们使用儿童年龄作为连续时间变量，建立了混合效应模型：结果：我们发现，随着时间的推移，MIA 与儿童的任何神经影像结果之间都没有明显的关联或时间交互作用。细胞因子指数、CRP 和单个细胞因子也存在类似的关联。经过多重检验校正后，我们没有观察到产前 MIA 时间或儿童性别的不同影响：这项以人群为基础的纵向研究没有发现 MIA 与普通人群中儿童大脑发育有关的证据。我们的研究结果与之前对新生儿进行的研究不同，这些新生儿在经历 MIA 后会出现大脑结构和功能异常。
期刊介绍：
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is an official journal of the Society for Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The journal publishes novel results of original research which represent an important new lead or significant impact on the field. Reviews and commentaries that focus on topics of current research and interest are also encouraged.
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