The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhood.
The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhood.
复制标题
妊娠期C反应蛋白水平升高对儿童晚期脑形态的长期影响
DOI：
10.1016/j.bbi.2022.03.018
复制
发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
动物研究表明，母体免疫激活（MIA）可能对胎儿大脑发育有不利影响。临床研究为MIA后人类新生儿的大脑结构异常提供了证据，但没有研究调查MIA（通过生物标志物测量）暴露十年后对人类大脑形态的长期影响。
我们的目的是评估MIA对10岁儿童大脑形态的长期影响，包括出生胎龄可能的中介作用。
我们利用了Generation R的数据，这是一项大规模的前瞻性孕期队列研究。2002年至2006年期间纳入孕妇，2013年至2015年期间邀请她们的孩子参加磁共振成像（MRI）研究。要纳入研究，母婴对必须有孕期母体C - 反应蛋白水平的数据以及孩子10岁时高质量的大脑MRI扫描数据。在接受扫描的3992名儿童中，共有2053名10岁儿童被纳入本研究。
在孕期前18周测量母体C - 反应蛋白。为了进行分析，我们既使用了连续方法，也使用了基于临床临界值的分类方法，以确定是否存在剂量 - 反应关系。
高分辨率MRI大脑形态测量作为主要结果。通过超声确定的出生胎龄作为中介因素，采用因果中介分析。对相关混杂因素进行了校正，并进行了多重比较。研究了生物性别作为调节因素。
我们发现连续的MIA与小脑体积减小之间存在直接关联。在女孩中，我们通过中介因素出生胎龄证明了连续的MIA与大脑总体积之间存在负向间接关联。经过多重检验校正后，我们未观察到与分类的MIA存在关联。
我们的结果表明MIA后大脑形态存在性别特异性的长期影响。分类分析表明，这种关联可能是由急性感染或其他严重炎症来源驱动的，鉴于新冠疫情目前正在影响全球数百万孕妇，这具有临床相关性。
Animal studies show that Maternal Immune Activation (MIA) may have detrimental effects on fetal brain development. Clinical studies provide evidence for structural brain abnormalities in human neonates following MIA, but no study has investigated the long-term effects of MIA (as measured with biomarkers) on human brain morphology ten years after the exposure. Our aim was to evaluate the long-term impact of MIA on brain morphology in 10-year-old children, including the possible mediating role of gestational age at birth. We leveraged data from Generation R, a large-scale prospective pregnancy cohort study. Pregnant women were included between 2002 and 2006, and their children were invited to participate in the MRI study between 2013 and 2015. To be included, mother-child dyads had to have data on maternal C-reactive protein levels during gestation and a good quality MRI-scan of the child’s brain at age 10 years. Of the 3,992 children scanned, a total of 2,053 10-year-old children were included in this study. Maternal C-reactive protein was measured in the first 18 weeks of gestation. For the analyses we used both a continuous approach as well as a categorical approach based on clinical cut-offs to determine if there was a dose-response relationship. High-resolution MRI brain morphology measures were used as the primary outcome. Gestational age at birth, established using ultrasound, was included as a mediator using a causal mediation analysis. Corrections were made for relevant confounders and multiple comparisons. Biological sex was investigated as moderator. We found a direct association between continuous MIA and lower cerebellar volume. In girls, we demonstrated a negative indirect association between continuous MIA and total brain volume, through the mediator gestational age at birth. We observed no associations with categorical MIA after multiple testing correction. Our results suggest sex-specific long-term effects in brain morphology after MIA. Categorical analyses suggest that this association might be driven by acute infections or or other sources of severe inflammation, which is of clinical relevance given that the COVID-19 pandemic is currently affecting millions of pregnant women worldwide.
登录
查看更多内容
影响因子：
4.3
作者：
D'Mello AM;Stoodley CJ
通讯作者：
Stoodley CJ
影响因子：
4.8
作者：
Bronson, Stefanie L.;Bale, Tracy L.
通讯作者：
Bale, Tracy L.
影响因子：
5.7
作者：
Fischl, Bruce
通讯作者：
Fischl, Bruce
影响因子：
26.1
作者：
El Marroun, Hanan;Zou, Runyu;Tiemeier, Henning
通讯作者：
Tiemeier, Henning
影响因子：
5.3
作者：
Bilbo SD;Block CL;Bolton JL;Hanamsagar R;Tran PK
通讯作者：
Tran PK