Sex-specific alterations in preterm brain

Abstract

Background: The literature on brain imaging in premature infants, is mostly made up of studies that evaluate neonates, yet the most dynamic time of brain development happens from birth to one year of age. This study was designed to obtain quantitative brain measures from Magnetic Resonance Imaging (MRI) scans of infants born prematurely at 12 months of age. Methods: The subject group was designed to capture a wide range of gestational age (GA) from premature to full term infants. An age-specific atlas generated quantitative brain measures. A regression model was used to predict effects of gestational age, sex, on brain measures. Results: There was a primary effect of sex on: 1) intracranial volume (ICV), males > females; 2) proportional cerebral cortical gray matter (females > males) and 3) cerebral white matter (males> females). GA predicted cerebral volume and cerebral spinal fluid (CSF). GA also predicted cortical gray matter in a sex specific manner with GA having a significant effect on cortical volume in the males, but not in females. Conclusions and Relevance: Sex differences in brain structure are large early in life. GA had sex specific effects highlighting the importance evaluating sex effects in neurodevelopmental outcomes of premature infants.

Development of sex differences in the human brain

“…Interestingly, the observed sex difference was already evident at the age of six, which corroborates other studies that have described sex differences in brain structure in children, babies, and even newborns (Benavides et al, 2019;Gilmore et al, 2007;Giedd et al, 2012;Lenroot & Giedd, 2010). These findings suggest an influence of early developmental factors, such as steroid hormones.…”

“…Importantly, sex differences in the brain do not only exist during adulthood, but are already present earlier in life (Berenbaum & Beltz, 2011, 2016Cosgrove et al, 2007;Hines, 2010;Giedd et al, 1999Giedd et al, , 2012Lenroot & Giedd, 2006, 2010Sacher et al, 2013). In fact, male and female brains have been reported to differ significantly in newborns and babies (Benavides et al, 2019;Gilmore et al, 2007), with more and more sex differences becoming evident during childhood and adolescence Herting & Sowell, 2017;Giedd et al, 2012;Tunc et al, 2016;Vijayakumar et al, 2018). This seems to suggest that males and females might be distinguishable based on sex differences in brain anatomy already early in life, with the sex gap further widening over the years.…”

Whole Brain and Cranial Size Adjustments in Volumetric Brain Analyses of Sex- and Age-Related Trends

“…In a large population of 949 youths Ingalhalikar et al (2014) found that for the females the relative GM volumes are larger than in the males, whereas the WM volumes are larger in the males. These differences were observed both in the children and adults (Benavides et al, 2019). Wierenga et al (2018) reported, in turn, a significantly higher variance for several brain structures among the males.…”

Quantitative MRI study of infant regional brain size following surgery for long‐gap esophageal atresia requiring prolonged critical care

“…While sex distributions in patient groups were balanced, the control group was predominantly comprised of males. Given reported sex‐dependent relationships of whole brain sizes (Benavides et al, 2019; Holland et al, 2014; Thompson et al, 2018), future studies with increased power should look into gender differences. Of note, one study found that normalization of regional brain volumes (%TBV) reportedly corrected for sex‐specific differences, with the exception of caudate and cerebellar vermis for which a Male < Female relationship persisted (Choe et al, 2013).…”