背景:妊娠期间母体感染已被确定为暴露后代精神病理学后期发展的产前危险因素。儿童时期收集的神经影像学数据表明,产前暴露于母体感染与儿童大脑结构和功能之间存在联系。可能为精神病理学的出现提供神经生物学解释。利用重复测量神经影像学数据的临床前研究进一步表明,产前母体感染对后代大脑的影响可能会随着时间的推移而正常化(即,追赶增长)。然而,目前尚不清楚人类产前母体感染是否与长期的分化神经发育轨迹有关.这项研究旨在使用重复测量的MRI数据调查产前暴露于感染对儿童大脑发育的影响。
方法:我们利用了基于人群的队列数据,R代,在这项研究中,我们前瞻性地评估了妊娠每三个月自我报告的感染情况(N=2,155).我们进一步使用了三种神经影像学评估(平均年龄6、10和14岁),以通过MRI获得后代脑形态的皮质和皮质下测量。此后,我们应用了线性混合效应模型,调整了几个混杂因素,估计随着时间的推移,母亲感染与儿童大脑发育的关系。
结果:我们发现,在妊娠晚期,产前暴露于感染与眼眶体积减少缓慢相关,前扣带和额上回,颞中回增加得更快。在时间极点,我们观察到了一种发散的模式,特别地,与暴露于较少感染的后代的体积减少相比,暴露于较多感染的后代的体积增加。我们进一步观察到其他额叶和颞叶结构在任何三个月暴露于感染后的关联,尽管这些没有在多次测试校正中幸存下来。
结论:我们的结果表明,妊娠晚期产前暴露于感染可能与以下地区的年龄相关生长较慢有关:眼眶,前扣带和额上回,以及童年时颞中回的更快生长,暗示了一个潜在的敏感期。我们的结果可能被解释为临床前研究的纵向发现的延伸,这表明暴露于产前感染的儿童可能表现出追赶生长。然而,考虑到基线时不同感染组之间的脑容量缺乏差异,可能有纵向偏差或细微的时间偏差。随后的良好动力的研究,延伸到整个大脑发育期(〜25年)需要确认是否观察到的现象确实是追赶增长,纵向偏差,或微妙的时间偏差。
BACKGROUND: Maternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring\'s brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data.
METHODS: We leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring\'s brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time.
RESULTS: We found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction.
CONCLUSIONS: Our results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.