Parental age effects on neonatal white matter development.,NeuroImage: Clinical

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Parental age effects on neonatal white matter development.
NeuroImage: Clinical ( IF 3.4 ) Pub Date : 2020-05-26 , DOI: 10.1016/j.nicl.2020.102283
Oliver Gale-Grant ₁ , Daan Christiaens ₂ , Lucilio Cordero-Grande ₂ , Andrew Chew ₂ , Shona Falconer ₂ , Antonios Makropoulos ₃ , Nicholas Harper ₂ , Anthony N Price ₂ , Jana Hutter ₂ , Emer Hughes ₂ , Suresh Victor ₂ , Serena J Counsell ₂ , Daniel Rueckert ₃ , Joseph V Hajnal ₂ , A David Edwards ₄ , Jonathan O'Muircheartaigh ₁ , Dafnis Batalle ₅

Affiliation

Objective

Advanced paternal age is associated with poor offspring developmental outcome. Though an increase in paternal age-related germline mutations may affect offspring white matter development, outcome differences could also be due to psychosocial factors. Here we investigate possible cerebral changes prior to strong environmental influences using brain MRI in a cohort of healthy term-born neonates.

Methods

We used structural and diffusion MRI images acquired soon after birth from a cohort (n = 275) of healthy term-born neonates. Images were analysed using a customised tract based spatial statistics (TBSS) processing pipeline. Neurodevelopmental assessment using the Bayley-III scales was offered to all participants at age 18 months. For statistical analysis neonates were compared in two groups, representing the upper quartile (paternal age ≥38 years) and lower three quartiles. The same method was used to assess associations with maternal age.

Results

In infants with older fathers (≥38 years), fractional anisotropy, a marker of white matter organisation, was significantly reduced in three early maturing anatomical locations (the corticospinal tract, the corpus callosum, and the optic radiation). Fractional anisotropy in these locations correlated positively with Bayley-III cognitive composite score at 18 months in the advanced paternal age group. A small but significant reduction in total brain volume was also observed in in the infants of older fathers. No significant associations were found between advanced maternal age and neonatal imaging.

Conclusions

The epidemiological association between advanced paternal age and offspring outcome is extremely robust. We have for the first time demonstrated a neuroimaging phenotype of advanced paternal age before sustained parental interaction that correlates with later outcome.

中文翻译：

父母年龄对新生儿白质发育的影响。

客观的

高龄父亲与后代发育不良有关。尽管父亲年龄相关种系突变的增加可能会影响后代白质发育，但结果差异也可能是由于心理社会因素造成的。在这里，我们使用脑部 MRI 对一组健康足月出生的新生儿进行了强烈环境影响之前可能发生的大脑变化研究。

方法

我们使用了一组健康足月新生儿 (n = 275) 出生后不久获得的结构和扩散 MRI 图像。使用基于定制区域的空间统计 (TBSS) 处理流程对图像进行分析。所有 18 个月大的参与者都接受了使用 Bayley-III 量表的神经发育评估。为了进行统计分析，对两组新生儿进行比较，分别代表上四分位数（父亲年龄≥38岁）和下四分位数。使用相同的方法评估与母亲年龄的关联。

结果

在父亲年龄较大（≥38岁）的婴儿中，分数各向异性（白质组织的标志）在三个早熟解剖位置（皮质脊髓束、胼胝体和视放射）显着降低。在高龄父亲组中，这些位置的分数各向异性与 18 个月时的 Bayley-III 认知综合评分呈正相关。在高龄父亲的婴儿中也观察到总脑容量有小幅但显着的减少。高龄产妇和新生儿影像学之间没有发现显着关联。