Sex differences in human brain anatomy have been well-documented; however, their underlying causes remain controversial. Neonatal research offers a pivotal opportunity to address this long-standing debate. Given that postnatal environmental influences (e.g., gender socialisation) are minimal at birth, any sex differences observed at this stage can be more readily attributed to prenatal influences. Here, we assessed on-average sex differences in global and regional brain volumes in 514 newborns (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. 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 higher total cortical gray matter volumes, whilst males showed higher total white matter volumes. After controlling for total brain volume in regional comparisons, females had 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 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. While postnatal experiences likely amplify sex differences in the brain, our findings demonstrate that several global and regional on-average sex differences are already present at birth.
