Sex Differences in Human Brain Structure at Birth

Biol Sex Differ. 2024 Oct 17;15(1):81. doi: 10.1186/s13293-024-00657-5.

Abstract

Background: Sex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.

Methods: Here, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0-28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.

Results: On average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).

Conclusions: Our findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.

Keywords: Brain development; Brain structure; Neonatal brain; Sex differences.

Plain language summary

Sex differences in the human brain have attracted substantial scientific and societal interest, but less is known about whether the brain shows sex differences at birth. Studying sex differences at birth can help to understand how prenatal factors (e.g., hormone levels before birth) and early postnatal factors (e.g., exposure to the sensory environment and caregiver interactions) contribute to shaping sex differences in the brain. In this study, we investigated on-average sex differences in brain structure in a large sample of newborn infants shortly after birth. Our findings show that several on-average differences are present at birth, suggesting that factors before birth play an important role in initiating sex differences in the brain.

MeSH terms

  • Brain* / anatomy & histology
  • Brain* / diagnostic imaging
  • Brain* / growth & development
  • Female
  • Humans
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Organ Size
  • Sex Characteristics*