Size at birth predicts later brain volumes

Abstract

We aimed to investigate whether gestation at birth, birth weight, and head circumference at birth are still associated with brain volume and white matter microstructure at 9-10 years in children born late-preterm and at term. One hundred and eleven children born at ≥ 36 weeks gestation from the CHYLD Study cohort underwent brain magnetic resonance imaging at 9 to 10 years. Images were analysed using FreeSurfer for volumetric data and tract-based spatial statistics for diffusion data. Of the cohort, 101 children were included for volumetric analysis [boys, 49(49%); median age, 9.5 (range: 8.9-12.4) years]. Shorter gestation at birth, lower birthweight, and smaller birth head circumference were associated with smaller brain volumes at 9 to 10 years, both globally and regionally. Amongst the perinatal factors studied, head circumference at birth was the strongest predictor of later brain volumes. Gestation at birth and absolute birthweight were not associated with diffusion metrics of white matter skeleton. However, lower birthweight z-score was associated with higher fractional anisotropy and lower radial diffusivity. Our findings suggest that even in children born late preterm and at term, growth before birth and timing of birth are still associated with brain development in mid-childhood.

Figure 1

Relationship between birthweight (a,b), head circumference at birth (c,d), and gestation at birth (e), and total brain volume at 9 to 10 years of age. Data are linear regressions with 95% confidence intervals shown as dotted lines. B = absolute beta coefficient (95% confidence interval).

Figure 2

Birthweight z-scores are negatively associated with FA (red) and positively associated with RD (blue) clusters in the white matter skeleton at 9 to 10 years of age. Significant clusters are overlaid on the Montreal Neurological Institute (MNI) T1-weighted template at 1-mm thickness and on the white matter skeleton (green). Red to yellow or blue to light blue indicates the size of the p values after correction for multiple comparisons using Threshold-Free Cluster Enhancement (TFCE). Images are sagittal (a), coronal (b), and axial (c) planes and displayed in radiological convention in which the right side of the brain is left on the image. For visualisation purposes, clusters in the whole brain skeleton with significant differences were thickened using tbss_fill towards the full width of the white matter tracts.