Preterm birth | EPFL Graph Search

Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 34 weeks, late preterm birth is between 34 and 36 weeks' gestation. These babies are also known as premature babies or colloquially preemies (American English) or premmies (Australian English). Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be. The cause of spontaneous preterm birth is often not known.

Methods for functional connectivity and morphometry in neonatal neuroimaging to study neurodevelopment.

Serafeim Loukas

Preterm birth is a major pediatric health problem that perturbs the genetically determined program of corticogenesis of the developing brain. As a consequence, prematurity has been strongly associated with adverse long-term neurodevelopmental outcome that may persist even into adulthood. Early characterization of the underlying neuronal mechanisms and early identification of infants at risk is of paramount importance since it allows better development of early therapeutic interventions aiming to prevent adverse outcomes through resilience. This dissertation aims to investigate the consequences of preterm birth on brain function and structure and their relation to adverse neurodevelopmental outcome, as well as to unveil the effect of an early music intervention on brain function. Research to date has mainly focused on the effect of early interventions on the long-term outcome but not on the effect of those interventions on brain function in preterm populations. Moreover, a clear consensus about the predictive utility of MRI volumetric data for long-term outcomes is still missing. This dissertation consists of three main parts. First, we investigate the effects of an early musical intervention in preterm infants using a task-based and resting-state fMRI paradigm. We explore brain effective connectivity changes during task and functional connectivity (FC) modulations at rest. We show that music exposure during hospitalization promotes brain auditory processing maturation. We find increased FC between the auditory cortex and regions involved in familiarity and music processing, such as the thalamus and caudate nucleus. Moreover, we report increased rs-FC in regions involved in associative memory and multisensory processing, such as the calcarine and angular gyrus with a dosage-dependent effect on this modulation. Secondly, we examine brain volumetric development and whether brain volumes are associated with cognitive and behavioural long-term outcomes. We find that perinatal risk factors, such as asphyxia and sepsis have an impact on brain tissue volume. We also find that cognitive and behavioural outcomes are strongly associated with parental SES and that brain tissue volumes at TEA have moderate predictive power. Next, inspired by studies that have characterized the progression of neurodegenerative diseases, we employ an advanced technique to unveil the sequence of biological events along the course of prematurity. Our novel findings might be of clinical use as they allow more targeted early interventions aiming to improve long-term outcomes. Finally, we propose a framework that enables the spectral graph theory analysis of the functional connectome at the voxel level. Our results indicate the presence of both functional gradients and community structure revealing fine-grained connectivity patterns. The proposed framework opens a new avenue for spectral graph theory research at the voxel level.

EPFL2021

Dynamics of brain function in preterm-born young adolescents

Lorena Gonçalves de Alcântara e Freitas Krikler

Preterm birth is a major risk factor for neurodevelopment impairments often only appearing later in life. The brain is still at a high rate of development during adolescence, making this a promising window for intervention. It is thus crucial to understand the mechanisms of altered brain function in this population. The aim of this thesis is to investigate how the brain dynamically reconfigures its own organisation over time in preterm-born young adolescents. Research to date has mainly focused on structural disturbances or in static features of brain function in this population. However, recent studies have shown that brain activity is highly dynamic, both spontaneously and during performance of a task, and that small disruptions in its complex architecture may interfere with normal behaviour and cognitive abilities. This thesis explores the dynamic nature of brain function in preterm-born adolescents in three steps: First, we investigate changes in spontaneous brain activity over time using a resting-state paradigm. Here, we study how the variability of the blood oxygenation level dependent signal (BOLD), a measure previously linked to cognitive performance, develops in a preterm- and a term-born groups. We find that preterm participants show an altered trajectory of BOLD variability development during early adolescence. We also show that the dynamic patterns of co-activation with the dorsal anterior cingulate cortex (ACC), a key node of the salience network, also develop differently between the preterm and control groups. Secondly, we examine task-driven changes in brain activation. To this end, we select a reality filtering task known to engage the orbitofrontal cortex (OFC), a region that is particularly vulnerable in the preterm. We find that, although the preterm group is able to perform the task successfully, OFC activation is significantly higher in the control participants. Finally, inspired by the successful field of dynamic functional connectivity which has mainly flourished in resting-state paradigms, we develop a novel method to look into task-driven modulations of brain connectivity in a time-resolved way. We then apply this new approach to a third data set involving a movie watching and emotion regulation task. We find several subtle but significant seed; task; and group effects that characterise each of the dynamic co-activation patterns. In short, we introduce a method for time-resolved evaluation of task-driven changes in brain connectivity and provide evidence of altered brain dynamics in preterm-born young adolescents. Our results thus highlight the importance of considering the dynamic aspects of brain function when studying clinical populations.

EPFL2020

Longitudinal study of neonatal brain tissue volumes in preterm infants and their ability to predict neurodevelopmental outcome

Laura Ioana Gui, Serafeim Loukas, Djalel Eddine Meskaldji

Premature birth has been associated with poor neurodevelopmental outcomes. However, the relation between such outcomes and brain growth in the neonatal period has not yet been fully elucidated. This study investigates longitudinal brain development between birth and term-equivalent age (TEA) by quantitative imaging in a cohort of premature infants born between 26 and 36 weeks gestational age (GA), to provide insight into the relation of brain growth with later neurodevelopmental outcomes. Longitudinal T2-weighted magnetic resonance images (MRI) of 84 prematurely born infants acquired shortly after birth and TEA were automatically segmented into cortical gray matter (CGM), unmyelinated white matter (UWM), subcortical gray matter (SGM), cerebellum (CB) and cerebrospinal fluid (CSF). General linear models and correlation analysis were used to study the relation between brain volumes and their growth, and perinatal variables. To investigate the ability of the brain volumes to predict children's neurodevelopmental outcome at 18-24 months and at 5 years of age, a linear discriminant analysis classifier was tested and several general linear models were fitted and compared by statistical tests. From birth to TEA, relative volumes of CGM, CB and CSF with respect to total intracranial volume increased, while relative volumes of UWM and SGM decreased. The fastest growing tissues between birth and TEA were found to be the CB and the CGM. Lower GA at birth was associated with lower growth rates of CGM, CB and total tissue. Among perinatal factors, persistent ductus arteriosus was associated with lower SGM, CB and IC growth rates, while sepsis was associated with lower CSF and intracranial volume growth rates. Model comparisons showed that brain tissue volumes at birth and at TEA contributed to the prediction of motor outcomes at 18-24 months, while volumes at TEA and volume growth rates contributed to the prediction of cognitive scores at 5 years of age. The family socio-economic status (SES) was not correlated with brain volumes at birth or at TEA, but was strongly associated with the cognitive outcomes at 18-24 months and 5 years of age. This study provides information about brain growth between birth and TEA in premature children with no focal brain lesions, and investigates their association with subsequent neurodevelopmental outcome. Parental SES was found to be a major determinant of neurodevelopmental outcome, unrelated to brain growth. However, further research is necessary in order to fully explain the variability of neurodevelopmental outcomes in this population.

ACADEMIC PRESS INC ELSEVIER SCIENCE2019