Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 16;14(9):e085365.
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 UK

James P Boardman  1   2 , Ruth Andrew  3 , Mark E Bastin  2 , Cheryl Battersby  4 , G David Batty  5 , Manuel Blesa Cábez  6   2 , Simon R Cox  7 , Jill Hall  6 , Lauren Ingledow  8 , Riccardo E Marioni  9 , Neena Modi  4 , Lee Murphy  10 , Alan J Quigley  11 , Rebecca M Reynolds  6   3 , Hilary Richardson  12 , Sarah J Stock  13 , Michael J Thrippleton  2 , Athanasios Tsanas  13   14 , Heather C Whalley  2
Affiliations

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

James P Boardman et al. BMJ Open. .

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).

Keywords: Developmental neurology & neurodisability; Immunity; Machine Learning; Magnetic Resonance Imaging; Neonatal intensive & critical care; Physiological Stress.

PubMed Disclaimer

Conflict of interest statement

Competing interests: REM is a scientific advisor to Optima Partners and the Epigenetic Clock Development Foundation. NM is the chief investigator for the National Neonatal Research Database. LM has received speaker and consultancy fees from Illumina.

Figures

Figure 1
Figure 1. PTB-RFs linked with altered cognition in children, proposed biological pathways that transmit risk to atypical brain development/outcome, and image biomarkers for delineating upstream pathways and predicting risk and resilience. BMI, body mass index; PTB-RFs, preterm birth-associated risk factors.
Figure 2
Figure 2. Codesigned PRENCOG logo, available in black and white.
Figure 3
Figure 3. Codesigned participant-facing infographic.
See this image and copyright information in PMC

References

    1. Lawn JE, Ohuma EO, Bradley E, et al. Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting. Lancet. 2023;401:1707–19. doi: 10.1016/S0140-6736(23)00522-6. - DOI - PubMed
    1. Volpe JJ. Dysmaturation of Premature Brain: Importance, Cellular Mechanisms, and Potential Interventions. Pediatr Neurol. 2019;95:42–66. doi: 10.1016/j.pediatrneurol.2019.02.016. - DOI - PubMed
    1. Johnson S, Marlow N. Early and long-term outcome of infants born extremely preterm. Arch Dis Child. 2017;102:97–102. doi: 10.1136/archdischild-2015-309581. - DOI - PubMed
    1. Blencowe H, Vos T, Lee AC, et al. Estimates of neonatal morbidities and disabilities at regional and global levels for 2010: introduction, methods overview, and relevant findings from the Global Burden of Disease study. Pediatr Res. 2013;74:4–16. doi: 10.1038/pr.2013.203. - DOI - PMC - PubMed
    1. Batalle D, Edwards AD, O’Muircheartaigh J. Annual Research Review: Not just a small adult brain: understanding later neurodevelopment through imaging the neonatal brain. J Child Psychol Psychiatry. 2018;59:350–71. doi: 10.1111/jcpp.12838. - DOI - PMC - PubMed

Publication types

LinkOut - more resources