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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.

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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.

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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.