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Published on: November 20, 2015
Parental age effects on neonatal white matter development
Oliver Gale-Grant1, Daan Christiaens2, Lucilio Cordero-Grande2
1Centre for the Developing Brain, School of Imaging Sciences & Biomedical Engineering, King's College London, United Kingdom; MRC Centre for Neurodevelopmental Disorders, King's College London, United Kingdom; Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom.
Insights
Advanced paternal age is linked to poorer child development. Neonatal brain MRI revealed altered white matter organization in infants of older fathers, correlating with later cognitive scores.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Pediatrics
Background:
- Advanced paternal age is a known risk factor for adverse offspring developmental outcomes.
- While genetic factors are implicated, the impact of early environmental influences remains unclear.
- Investigating neonatal brain development can elucidate pre-environmental effects of paternal age.
Purpose of the Study:
- To investigate cerebral changes in healthy term-born neonates using brain MRI.
- To identify neuroimaging phenotypes associated with advanced paternal age before significant environmental exposure.
- To correlate neonatal brain findings with later neurodevelopmental assessments.
Main Methods:
- Structural and diffusion MRI scans were acquired from 275 healthy term-born neonates.
- Tract-based spatial statistics (TBSS) pipeline was used for image analysis.
- Neonates were grouped by paternal age (≥38 years vs. younger fathers); maternal age was also assessed. Bayley-III scales used for 18-month assessments.
Main Results:
- Infants of fathers ≥38 years showed significantly reduced fractional anisotropy (FA) in the corticospinal tract, corpus callosum, and optic radiation.
- Reduced FA in these areas positively correlated with cognitive scores at 18 months in the advanced paternal age group.
- A slight but significant reduction in total brain volume was observed in infants of older fathers; no association with advanced maternal age.
Conclusions:
- Advanced paternal age is associated with a distinct neuroimaging phenotype in neonates.
- This phenotype, characterized by white matter alterations, precedes significant environmental influences and correlates with later cognitive development.
- Findings provide novel insights into the early biological impact of paternal age on offspring brain development.
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.
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