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Sex effects on cortical alterations in infants with complex congenital heart disease

Xuyun Wen1,2, Pengcheng Xue1,2, Siyu Ma3

  • 1Department of Intelligent Interdisciplinary Applications, College of Artificial Intelligence, Nanjing University of Aeronautics and Astronautics, Jiangjun Road, Jiangning District, Nanjing 211106, Jiangsu, China.

Cerebral Cortex (New York, N.Y. : 1991)
|December 27, 2025
PubMed

Insights

Male infants with congenital heart disease (CHD) show greater brain volume reduction and motor skill deficits than females. Understanding these sex differences is crucial for developing targeted neuroprotective strategies for CHD patients.

Area of Science:

  • Neuroscience
  • Pediatrics
  • Developmental Biology

Background:

  • Congenital heart disease (CHD) significantly impacts neurodevelopmental outcomes.
  • Sex is a critical factor, with males often exhibiting more severe impairments.
  • Limited research exists on sex-specific early brain development in infants with CHD.

Purpose of the Study:

  • To investigate sex-specific effects on brain development in infants with complex congenital heart disease.
  • To identify distinct patterns of global and regional brain alterations between male and female CHD infants.
  • To correlate brain development differences with neurodevelopmental outcomes.

Main Methods:

  • Magnetic resonance imaging (MRI) data collection from 79 infants with complex CHD (42 males, 37 females) and 87 healthy controls (47 males, 40 females).
  • Analysis of global and regional brain volumes, cortical thickness, gray matter volume, and surface area.
  • Statistical analysis to examine sex-specific effects and associations with neurodevelopmental assessments.

Main Results:

  • Male CHD infants displayed reduced global brain volume and regional cortical delays (increased thickness, gray matter volume).
  • Female CHD infants showed localized abnormalities (reduced surface area, increased thickness) without significant global volume changes.
  • Reduced global brain volume in males correlated with poorer gross motor skills.

Conclusions:

  • Significant sex differences in brain development are evident in early life among infants with congenital heart disease.
  • These distinct neuroanatomical patterns highlight the need for sex-specific approaches in managing CHD.
  • Tailored neuroprotective strategies are essential for optimizing neurodevelopmental outcomes in CHD populations.

Keywords:
brain developmentcongenital heart diseaseinfantneurodevelopmental outcomesex

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