Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom

James P Boardman; Ruth Andrew; Mark E Bastin; Cheryl Battersby; G David Batty; Manuel Blesa Cabez; Simon R Cox; Jill Hall; Lauren Ingledow; Riccardo E Marioni; Neena  Modi; Lee Murphy; Alan J Quigley; Rebecca M Reynolds; Hilary Richardson; Sarah J Stock; Michael J Thrippleton; Athanasios Tsanas; Heather C Whalley

doi:10.1136/bmjopen-2024-085365

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom

James P Boardman^*, Ruth Andrew, Mark E Bastin, Cheryl Battersby, G David Batty, Manuel Blesa Cabez, Simon R Cox, Jill Hall, Lauren Ingledow, Riccardo E Marioni, Neena Modi, Lee Murphy, Alan J Quigley, Rebecca M Reynolds, Hilary Richardson, Sarah J Stock, Michael J Thrippleton, Athanasios Tsanas, Heather C Whalley

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP.

Methods and analysis PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother–infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.

EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database.

Ethics and dissemination A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

Original language	English
Article number	e085365
Journal	BMJ Open
Volume	14
Issue number	9
DOIs	https://doi.org/10.1136/bmjopen-2024-085365
Publication status	Published - 16 Sept 2024

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e085365.fullFinal published version, 2.78 MBLicence: Creative Commons: Attribution (CC-BY)

Preterm birth, Neurodevelopment and Cognition in Children: Causal Evidence and Mechanisms
Boardman, J. (Principal Investigator), Cox, S. (Co-investigator), Marioni, R. (Co-investigator), Reynolds, R. (Co-investigator), Richardson, H. (Co-investigator), Tsanas, T. (Co-investigator) & Whalley, H. (Co-investigator)
Medical Research Council
1/11/22 → 31/10/27
Project: Research

Genetics Core, Edinburgh Clinical Research Facility
Murphy, L. (Manager), Fawkes, A. (Other), Hafezi, K. (Other), Clark, R. (Other), MacCallum, A. (Other), Aitken, E. (Other) & Macgillivray, L. (Other)
Deanery of Clinical Sciences
Facility/equipment: Facility

Cite this

Boardman, J. P., Andrew, R., Bastin, M. E., Battersby, C., David Batty, G., Blesa Cabez, M., Cox, S. R., Hall, J., Ingledow, L., Marioni, R. E., Modi, N., Murphy, L., Quigley, A. J., Reynolds, R. M., Richardson, H., Stock, S. J., Thrippleton, M. J., Tsanas, A., & Whalley, H. C. (2024). Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom. BMJ Open, 14(9), Article e085365. https://doi.org/10.1136/bmjopen-2024-085365

@article{7f77657f005b4aa8b750cf57c9bca935,

title = "Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom",

abstract = "Introduction Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP.Methods and analysis PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother–infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database.Ethics and dissemination A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).",

author = "Boardman, {James P} and Ruth Andrew and Bastin, {Mark E} and Cheryl Battersby and {David Batty}, G and {Blesa Cabez}, Manuel and Cox, {Simon R} and Jill Hall and Lauren Ingledow and Marioni, {Riccardo E} and Neena Modi and Lee Murphy and Quigley, {Alan J} and Reynolds, {Rebecca M} and Hilary Richardson and Stock, {Sarah J} and Thrippleton, {Michael J} and Athanasios Tsanas and Whalley, {Heather C}",

year = "2024",

month = sep,

day = "16",

doi = "10.1136/bmjopen-2024-085365",

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number = "9",

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Boardman, JP , Andrew, R , Bastin, ME, Battersby, C, David Batty, G, Blesa Cabez, M , Cox, SR , Hall, J, Ingledow, L, Marioni, RE, Modi, N, Murphy, L, Quigley, AJ, Reynolds, RM , Richardson, H , Stock, SJ , Thrippleton, MJ , Tsanas, A & Whalley, HC 2024, 'Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom', BMJ Open, vol. 14, no. 9, e085365. https://doi.org/10.1136/bmjopen-2024-085365

TY - JOUR

T1 - Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom

AU - Boardman, James P

AU - Andrew, Ruth

AU - Bastin, Mark E

AU - Battersby, Cheryl

AU - David Batty, G

AU - Blesa Cabez, Manuel

AU - Cox, Simon R

AU - Hall, Jill

AU - Ingledow, Lauren

AU - Marioni, Riccardo E

AU - Modi, Neena

AU - Murphy, Lee

AU - Quigley, Alan J

AU - Reynolds, Rebecca M

AU - Richardson, Hilary

AU - Stock, Sarah J

AU - Thrippleton, Michael J

AU - Tsanas, Athanasios

AU - Whalley, Heather C

PY - 2024/9/16

Y1 - 2024/9/16

N2 - Introduction Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP.Methods and analysis PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother–infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database.Ethics and dissemination A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

AB - Introduction Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP.Methods and analysis PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother–infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database.Ethics and dissemination A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

U2 - 10.1136/bmjopen-2024-085365

DO - 10.1136/bmjopen-2024-085365

M3 - Article

SN - 2044-6055

VL - 14

JO - BMJ Open

JF - BMJ Open

IS - 9

M1 - e085365

ER -

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the United Kingdom

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Preterm birth, Neurodevelopment and Cognition in Children: Causal Evidence and Mechanisms

Equipment

Genetics Core, Edinburgh Clinical Research Facility

Cite this