Sex differences in brain structure are present at birth and remain stable during early development

New research published in Biology of Sex Differences has found that sex differences in brain structure are already present at birth and remain relatively stable during early postnatal development. The study found that while male infants tend to have larger total brain volumes, female infants, when adjusted for brain size, have more grey matter, whereas male infants have more white matter. These findings suggest that prenatal biological factors play a significant role in shaping early sex differences in brain structure.

Researchers have long been interested in how male and female brains differ, but the origins of these differences have remained uncertain. While studies have documented sex differences in brain structure in older children and adults, it has been unclear whether these differences are present at birth or whether they emerge later due to environmental and social influences. Understanding when sex differences first appear in the brain can help researchers determine whether they are primarily shaped by prenatal biological factors or by early-life experiences.

The question is particularly important because many neurological and psychiatric conditions, such as autism, attention deficit hyperactivity disorder, and depression, show differences in prevalence and symptoms between males and females. If some of these differences are rooted in early brain development, studying the neonatal brain may provide new insights into the biological foundations of these conditions.

Previous research on brain development in infants has been limited, with most studies including infants older than one month. The new study aimed to fill that gap by examining newborns in the first four weeks of life, a period of rapid brain development. By studying infants so early, researchers hoped to gain a clearer picture of the biological factors that contribute to sex differences in brain structure.

“Sex differences in the brain are a topic of both scientific and public interest, but our interest in the area is also driven by their practical significance,” explained study author Yumnah Khan, a PhD student at the University of Cambridge.

“A vast majority of psychiatric and neurodevelopmental conditions show sex differences in prevalence or presentation, and it is hypothesized that these arise due to sex differences in the brain. A better understanding of sex differences, their underlying causes, and the timeline of their emergence can explain why this is the case. This may also ultimately help towards tailoring diagnostic and support strategies to facilitate optimal health outcomes.”

To explore sex differences in neonatal brain structure, the researchers analyzed data from 514 healthy, full-term newborns who were part of the Developing Human Connectome Project. The sample included 278 male and 236 female infants who were scanned within the first 28 days of life. The researchers used magnetic resonance imaging (MRI) to measure brain volume and analyze differences between male and female infants.

The MRI scans were conducted while the infants were naturally asleep and swaddled to minimize movement. No sedation was used. The researchers measured total brain volume as well as the volume of grey and white matter. Grey matter consists of brain regions responsible for processing information, while white matter consists of the neural pathways that connect different parts of the brain.

The study also accounted for factors such as birth weight, which is known to be slightly higher in male infants on average. By adjusting for these factors, the researchers aimed to isolate the effects of biological sex on brain structure.

The findings confirmed that male infants had larger total brain volumes compared to female infants, a pattern that has been consistently reported in older children and adults. However, when researchers adjusted for overall brain size, they found that female infants had significantly more grey matter, while male infants had more white matter.

Further analysis of specific brain regions showed that, even after accounting for differences in total brain volume, certain areas were larger in female infants, while others were larger in male infants. Female infants had relatively greater volumes in regions such as the corpus callosum, which connects the two hemispheres of the brain, and the parahippocampal gyrus, an area involved in memory processing. Male infants had larger volumes in regions such as the medial and inferior temporal gyri, which are associated with visual and auditory processing.

“Several on-average sex differences in the brain are already present from birth, indicating that prenatal factors play an important role in initiating sex differences in the brain,” Khan told PsyPost.

Importantly, the study found that these sex differences remained stable during the first month of life, suggesting that they were already established at birth rather than emerging as a result of early postnatal experiences. While some regions showed slight changes over time, the overall pattern of differences between male and female infants did not significantly shift.

“We found it very interesting that several of the sex differences that were previously observed in older children and adults were already present at birth,” Khan said. “This emphasises that these differences are present from the very beginning of life and likely emerge prenatally.”

While this study provides evidence that sex differences in brain structure are present at birth, there are some limitations to consider. The study was not designed to investigate the causes of these differences, meaning it remains unclear whether they are primarily driven by genetic factors, prenatal hormone exposure, or other influences during fetal development. Additionally, while the study identified structural differences, it did not examine whether these differences are linked to cognitive or behavioral traits.

The researchers also emphasize that, while group-level differences exist, they do not imply that male and female brains are fundamentally different in function. The observed differences are based on averages across large samples, and individual variation is substantial. In other words, while certain patterns may be more common in one sex, they do not apply universally to every male or female infant.

“It is important not to overstate or exaggerate the differences,” Khan explained. “The brain is not ‘sexually dimorphic’ the way that the reproductive organs are. The brains of males and females are more similar than they are different. Any sex differences that we have observed here are simply in group averages, and may not apply to each individual male or female.”

“There is still much more to uncover,” she added. “Although we now know that there are sex differences in brain structure at birth, one of the most pressing questions is whether there are also observable sex differences in behavior and cognition from birth. Secondly, it is important to identify whether sex differences in the brain at birth are actually linked to sex differences in behavior/cognition, and also whether they are linked to sex differences in future developmental outcomes (potentially explaining why several psychiatric and neurodevelopmental conditions show sex differences in prevalence and presentation). Finally, we would also like to understand what the exact causes that lead to sex differences in the brain at birth.”

The study, “Sex Differences in Human Brain Structure at Birth,” was authored by Yumnah T. Khan, Alex Tsompanidis, Marcin A. Radecki, Lena Dorfschmidt, APEX Consortium, Topun Austin, John Suckling, Carrie Allison, Meng-Chuan Lai, Richard A. I. Bethlehem, and Simon Baron-Cohen.