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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

Preterm 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 analysis

Theirworld 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 dissemination

Ethical 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.

Related collections

Most cited references 35

Record: found
Abstract: found
Article: not found

Neonatal MRI to predict neurodevelopmental outcomes in preterm infants.

Lianne J Woodward, Peter Anderson, Nicola Austin … (2006)

Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive delay (odds ratio, 3.6; 95 percent confidence interval, 1.5 to 8.7), motor delay (odds ratio, 10.3; 95 percent confidence interval, 3.5 to 30.8), cerebral palsy (odds ratio, 9.6; 95 percent confidence interval, 3.2 to 28.3), and neurosensory impairment (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.3). Gray-matter abnormalities (present in 49 percent of infants) were also associated, but less strongly, with cognitive delay, motor delay, and cerebral palsy. Moderate-to-severe white-matter abnormalities on MRI were significant predictors of severe motor delay and cerebral palsy after adjustment for other measures during the neonatal period, including findings on cranial ultrasonography. Abnormal findings on MRI at term equivalent in very preterm infants strongly predict adverse neurodevelopmental outcomes at two years of age. These findings suggest a role for MRI at term equivalent in risk stratification for these infants. Copyright 2006 Massachusetts Medical Society.

0 comments Cited 257 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization Pneumococcal Carriage Working Group.

Catherine Satzke, Paul Turner, Anni Virolainen-Julkunen … (2013)

In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal samples, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches. We outline the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies. Adherence to these methods will reduce variability in the conduct of pneumococcal carriage studies undertaken in the context of pneumococcal vaccine trials, implementation studies, and epidemiology studies more generally so variability in methodology does not confound the interpretation of study findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

0 comments Cited 204 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Abnormal cerebral structure is present at term in premature infants.

Simon Warfield, T Inder, Petra Hüppi … (2005)

Long-term studies of the outcome of very prematurely born infants have clearly documented that the majority of such infants have significant motor, cognitive, and behavioral deficits. However, there is a limited understanding of the nature of the cerebral abnormality underlying these adverse neurologic outcomes. The overall aim of this study was to define quantitatively the alterations in cerebral tissue volumes at term equivalent in a large longitudinal cohort study of very low birth weight premature infants in comparison to term-born infants by using advanced volumetric 3-dimensional magnetic resonance imaging (MRI) techniques. We also aimed to define any relationship of such perinatal lesions as white matter (WM) injury or other potentially adverse factors to the quantitative structural alterations. Additionally, we wished to identify the relationship of the structural alterations to short-term neurodevelopmental outcome. From November 1998 to December 2000, 119 consecutive premature infants admitted to the neonatal intensive care units at Christchurch Women's Hospital (Christchurch, New Zealand) and the Royal Women's Hospital (Melbourne, Australia) were recruited (88% of eligible) after informed parental consent to undergo an MRI scan at term equivalent. Twenty-one term-born infants across both sites were recruited also. Postacquisition advanced 3-dimensional tissue segmentation with 3-dimensional reconstruction was undertaken to estimate volumes of cerebral tissues: gray matter (GM; cortical and deep nuclear structures), WM (myelinated and unmyelinated), and cerebrospinal fluid (CSF). In comparison to the term-born infants, the premature infants at term demonstrated prominent reductions in cerebral cortical GM volume (premature infants [mean +/- SD]: 178 +/- 41 mL; term infants: 227 +/- 26 mL) and in deep nuclear GM volume (premature infants: 10.8 +/- 4.1 mL; term infants: 13.8 +/- 5.2 mL) and an increase in CSF volume (premature infants: 45.6 +/- 22.1 mL; term infants: 28.9 +/- 16 mL). The major predictors of altered cerebral volumes were gestational age at birth and the presence of cerebral WM injury. Infants with significantly reduced cortical GM and deep nuclear GM volumes and increased CSF volume volumes exhibited moderate to severe neurodevelopmental disability at 1 year of age. This MRI study of prematurely born infants further defines the nature of quantitative cerebral structural abnormalities present as early as term equivalent. The abnormalities particularly involve cerebral neuronal regions including both cortex and deep nuclear structures. The pattern of cerebral alterations is related most significantly to the degree of immaturity at birth and to concomitant WM injury. The alterations are followed by abnormal short-term neurodevelopmental outcome.

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2020

Publication date (Electronic): 4 March 2020

Volume: 10

Issue: 3

Electronic Location Identifier: e035854

Affiliations

[1 ]departmentMRC Centre for Reproductive Health , The University of Edinburgh , Edinburgh, UK

[2 ]departmentCentre for Clinical Brain Sciences , The University of Edinburgh , Edinburgh, UK

[3 ]departmentEdinburgh Imaging , The University of Edinburgh , Edinburgh, UK

[4 ]departmentCentre for Cardiovascular Science , The University of Edinburgh , Edinburgh, UK

[5 ]departmentCentre for Inflammation Research , The University of Edinburgh , Edinburgh, UK

Author notes

[Correspondence to ] Professor James P Boardman; James.Boardman@ 123456ed.ac.uk

Author information

James P Boardman http://orcid.org/0000-0003-3904-8960

Article

Publisher ID: bmjopen-2019-035854

DOI: 10.1136/bmjopen-2019-035854

PMC ID: 7059503

PubMed ID: 32139495

SO-VID: 1e14d2ac-ae6b-46cf-80b8-2912a140602a

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

History

Date received : 19 November 2019

Date revision received : 16 January 2020

Date accepted : 12 February 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;

Award ID: 104916/Z/14/Z

Award ID: 203769/Z/16/A

Award ID: 220043/Z/19/Z

Funded by: FundRef http://dx.doi.org/10.13039/100010898, Edinburgh and Lothians Health Foundation;

Award ID: 2012/17

Funded by: FundRef http://dx.doi.org/10.13039/501100000589, Chief Scientist Office;

Award ID: SCAF/16/03

Award ID: TCS/18/02

Funded by: FundRef http://dx.doi.org/10.13039/501100000317, Action Medical Research;

Award ID: GN2703

Funded by: FundRef http://dx.doi.org/10.13039/501100000265, Medical Research Council;

Award ID: G1002033

Funded by: FundRef http://dx.doi.org/10.13039/501100000377, Dunhill Medical Trust;

Award ID: R380R/1114

Funded by: Theirworld;

Funded by: FundRef http://dx.doi.org/10.13039/501100000274, British Heart Foundation;

Award ID: RE/18/5/34216

Custom metadata

special-feature unlocked

ScienceOpen disciplines: Medicine

Keywords: neonatal intensive & critical care,paediatric neurology,maternal medicine,developmental neurology & neurodisability,child & adolescent psychiatry,mri

Data availability:

ScienceOpen disciplines: Medicine

Keywords: neonatal intensive & critical care, paediatric neurology, maternal medicine, developmental neurology & neurodisability, child & adolescent psychiatry, mri

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

Read this article at

Abstract

Introduction

Methods and analysis

Ethics and dissemination

Related collections

Stroke MRI

Most cited references 35

Neonatal MRI to predict neurodevelopmental outcomes in preterm infants.

Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization Pneumococcal Carriage Working Group.

Abnormal cerebral structure is present at term in premature infants.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 301

Cited by 15

Most referenced authors 591