Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth

Abstract

BackgroundWe postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.Methods and FindingsWe analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth.ConclusionsHuman brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction

“…Numerous works have been published in the literature that have improved our understanding of the perinatal brain (Ball et al, 2013b(Ball et al, , 2017Counsell et al, 2013;Doria et al, 2010;Kapellou et al, 2006;Keunen et al, 2017;Krishnan et al, 2017;Xue et al, 2007;Dubois et al, 2008a,b;Pienaar et al, 2008;RodriguezCarranza et al, 2008;Awate et al, 2010;Hill et al, 2010;Rathbone et al, 2011;Moeskops et al, 2013;Li et al, 2014b,a;Meng et al, 2014;Nie et al, 2014;Wang et al, 2014;Engelhardt et al, 2015;Lefevre et al, 2015;Li et al, 2015b;Moeskops et al, 2015;Li et al, 2016;Hazlett et al, 2017). Study- ing the developing connectome will open up many opportunities in future, not least because neonatal brain imaging data is changing rapidly, at scales that can be clearly resolved using current MRI technology.…”

The emergence of functional architecture during early brain development

“…While axons continue to grow, facilitating major connections in the white matter to find their cortical targets, the overlying cortex transforms its relatively smooth surface into a highly convoluted mantle with secondary and tertiary sulci that resembles the adult human brain (Stiles and Jernigan, 2010;Striedter et al, 2014). MRI studies in preterm infants have reported a five-fold increase in cortical surface area and doubling of cortical curvature measures in the timeframe that coincides with the third trimester of pregnancy (Ajayi-Obe et al, 2000;Dubois et al, 2008;Kapellou et al, 2006;Moeskops et al, 2015).…”

Educational Outcomes in Extremely Preterm Children: Neuropsychological Correlates and Predictors of Attainment

“…A normal cerebral ultrasound scan and larger OFC at 30 months corrected age were both associated with higher reading and mathematics scores. This may reflect perinatal insults to the developing brain or the impact of EP birth on normal brain growth and development (Kapellou et al, 2006;Peterson et al, 2000Peterson et al, , 2006.…”