Suleri Anna, Rommel Anna-Sophie, Dmitrichenko Olga, Muetzel Ryan L, Cecil Charlotte A M, de Witte Lot, Bergink Veerle
Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, The Netherlands.
The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands.
Mol Psychiatry. 2025 Feb;30(2):722-735. doi: 10.1038/s41380-024-02760-w. Epub 2024 Sep 28.
Maternal immune activation (MIA) during pregnancy, as a result of infectious or inflammatory stimuli, has gained increasing attention for its potential role in adverse child neurodevelopment, with studies focusing on associations in children born preterm. This systematic review summarizes research on the link between several types of prenatal MIA and subsequent child structural and/or functional brain development outcomes. We identified 111 neuroimaging studies in five MIA areas: inflammatory biomarkers (n = 13), chorioamnionitis (n = 18), other types of infections (n = 18), human immunodeficiency virus (HIV) (n = 42), and Zika virus (n = 20). Overall, there was large heterogeneity in the type of MIA exposure examined and in study methodology. Most studies had a prospective single cohort design and mainly focused on potential effects on the brain up to one year after birth. The median sample size was 53 participants. Severe infections, i.e., HIV and Zika virus, were associated with various types of cerebral lesions (e.g., microcephaly, atrophy, or periventricular leukomalacia) that were consistently identified across studies. For less severe infections and chronic inflammation, findings were generally inconsistent and mostly included deviations in white matter structure/function. Current findings have been mainly observed in the infants' brain, presenting an opportunity for future studies to investigate whether these associations persist throughout development. Additionally, the inconsistent findings, encompassing both regions of interest and null results, call into question whether prenatal exposure to less severe infections and chronic inflammation exerts a small effect or no effect on child brain development.
孕期母体免疫激活（MIA），由于感染或炎症刺激，因其在儿童不良神经发育中的潜在作用而受到越来越多的关注，研究主要聚焦于早产出生儿童中的关联。本系统综述总结了几种类型的产前MIA与随后儿童大脑结构和/或功能发育结果之间联系的研究。我们在五个MIA领域确定了111项神经影像学研究：炎症生物标志物（n = 13）、绒毛膜羊膜炎（n = 18）、其他类型感染（n = 18）、人类免疫缺陷病毒（HIV）（n = 42）和寨卡病毒（n = 20）。总体而言，所研究的MIA暴露类型和研究方法存在很大异质性。大多数研究采用前瞻性单队列设计，主要关注出生后一年内对大脑的潜在影响。样本量中位数为53名参与者。严重感染，即HIV和寨卡病毒，与各类脑损伤（如小头畸形、萎缩或脑室周围白质软化）相关，这些脑损伤在各项研究中均得到一致确认。对于不太严重的感染和慢性炎症，研究结果普遍不一致且大多包括白质结构/功能的偏差。目前的研究结果主要在婴儿大脑中观察到，这为未来研究调查这些关联是否在整个发育过程中持续存在提供了契机。此外，研究结果不一致，既有感兴趣区域的发现，也有阴性结果，这让人质疑产前暴露于不太严重的感染和慢性炎症对儿童大脑发育是否产生微小影响或没有影响。
