Preterm birth and structural brain alterations in early adulthood

Abstract

Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior corpus callosum/thalamus/fornix and GM volume in temporal gyri bilaterally, accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These results reveal that VPT birth continues to be associated with altered structural brain anatomy in early adult life, although it remains to be ascertained whether these changes reflect neurodevelopmental delays or long lasting structural alterations due to prematurity. GM and WM alterations correlate with length of gestation and mediate cognitive outcome.

Early life characteristics, social mobility during childhood and risk of stroke in later life: findings from a Swedish cohort

“…Moreover, very preterm birth is associated with structural brain alterations in early adulthood, whereby volumetric differences in grey matter and white matter are linearly associated with gestational length. [23] It is possible that these persisting anatomical differences lead to an increased risk of stroke in individuals born preterm in our cohort.…”

30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis

“…This latter was surprising since the sequelae of hypoxia and other fetal hazards can readily be seen in the brains of nonpsychotic adults who had been born very preterm. 17 In retrospect, it seems that the developmental changes are masked in people with schizophrenia by the effects of antipsychotics and lifestyle factors such as illicit drug abuse on the brain. 18 As exception is abnormal gyrification which remains a marker of aberrant foetal development in schizophrenia and is associated with lack of treatment response.…”

Reduced Cholinergic Basal Forebrain Integrity Links Neonatal Complications and Adult Cognitive Deficits After Premature Birth

“…While our analyses demonstrate a relatively specific role of the cBF in premature birth-associated cognitive deficits that last into adulthood, one would not expect cBF volume to be the only factor related to variance in intellectual abilities among VP/VLBW adults. This is also reflected in the mild to moderate effect size of the observed associations between cBF volume and IQ scores (rpart = 0.26 -0.33), indicating that impairments in other cortical and/or subcortical regions and their networking through the brain's white matter may affect intellectual abilities in VP/VLBW adults in at least partially independent ways (12,34,35). In addition, associations between structural/volumetric brain markers and mental capacities are generally indirect in nature and depend on the degree to which the measured structural abnormalities reflect the functional integrity of the neuronal system under study.…”

“…However, in our sample of VP/VLBW adults, total WM volume was only marginally reduced compared to controls and was not related to intellectual impairments. While studies on premature birth-associated cerebral abnormalities in adulthood are still rare, two recent volumetric imaging studies on independent cohorts of VP/VLBW adults (34,35) reported very similar observations of more subtle between-group differences compared to the data in infants (31,32) and adolescents (11,29,33). Thus, rather than showing global differences, structural abnormalities in VP/VLBW adults were found to be restricted to specific subcortical GM and WM structures and select cortical limbic and associative regions, indicating that some, but not all, aspects of the adverse effects of premature birth on cerebral structure may normalize during late development.…”

“…Accordingly, variance in hippocampus volume has been shown to exhibit robust in-vivo associations with memory performance across a wide range of neurologic conditions (24,42), but not so in healthy adults (43). In addition, the association between cBF volume and cognitive performance may be augmented by comorbid brain lesions in the VP/VLBW group (12,(34)(35)(36). Thus, experimental animal research (44) and more recent human in-vivo studies (45) have implicated impaired cBF integrity in diminished neural adaptation to white matter injury, possibly further contributing to worse cognitive outcomes in VP/VLBW adults.…”