Impact of preterm birth on brain development and long-term outcome: protocol for a cohort study in Scotland

Abstract

IntroductionPreterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data.Methods and analysisTheirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic–pituitary–adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome.Ethics and disseminationEthical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit.

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

“…We reported an association between deviations from normative brain development at TEA and behaviour at 18-20 months. An important step for future research is to investigate whether these early brain deviations persist in later life and are predictive of childhood and later neurodevelopment (Boardman et al 2020; George et al 2020).…”

Maternal cortisol is associated with neonatal amygdala microstructure and connectivity in a sexually dimorphic manner

“…A Siemens MAGNETOM Prisma 3 T MRI clinical scanner (Siemens Healthcare Erlangen, Germany) and 16-channel phased-array paediatric head and neck coil were used for acquisition ( Boardman et al, 2020 ). In brief, we acquired 3D T1-weighted MPRAGE (T1w) (acquired voxel size = 1 mm isotropic) with TI 1100 ms, TE 4.69 ms and TR 1970 ms; 3D T2-weighted SPACE (T2w) (voxel size = 1 mm isotropic) with TE 409 ms and TR 3200 ms; and axial dMRI.…”

Peak Width of Skeletonized Water Diffusion MRI in the Neonatal Brain

“…Participants were recruited as part of a longitudinal study designed to investigate the effects of preterm birth on brain structure and long term outcome (www.tebc.ed.ac.uk) (21). One hundred and thirty-five neonates underwent MRI at term equivalent age at the Edinburgh Imaging Facility: Royal Infirmary of Edinburgh, University of Edinburgh, UK.…”