Cardiovascular Health Assessment of Preterm- and TERm-born Children (CHAPTER)

The purpose of the CHAPTER study is to help understand how complications during pregnancy, such as preterm birth, affect how childrens' hearts and blood vessels develop.

Study Overview

• Status: Enrolling by invitation
• Conditions: Premature Birth

Detailed Description

Young adults born preterm (less than 37 weeks gestation) have alterations in the structure and function of the heart, with similar changes observed in preterm infants in the first three months of life. It is unknown whether these early changes in the heart seen in the first few months of life are relevant to long-term changes in heart structure and function. Heart changes have also not been well studied in children born preterm. To investigate this, the study will follow up children from the EPOCH study and will perform two study visits for each child (n=100 preterm and n=100 term) that will use echocardiography and cardiovascular magnetic resonance. Individuals in the EPOCH study had echocardiography measures done at birth and three months postnatal age. It will therefore be possible to do longitudinal echocardiography measures from birth up to ages 12 years to determine whether postnatal heart changes in preterm infants track into childhood. Cardiovascular magnetic resonance will allow for the determination of whether these early heart changes influence heart pump function. Finally, by measuring lung function, blood vessel structure and function, and blood pressure, it will be possible to determine how heart changes relate to other components of the cardiovascular system. This data will be used to confirm the relevance of early heart remodelling in preterm-born offspring over time and provide more comprehensive heart phenotyping for preterm-born children. Together, this information can be used to design future intervention strategies in preterm-born individuals to reduce cardiovascular risk in this growing subgroup of the population.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 9DU
    • University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 9 years (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children aged 3--12 years old born preterm (less than 37 weeks gestation) or term (37--42 weeks gestation) delivered at or admitted to the Oxford University Hospitals NHS Foundation Trust who took part in the EPOCH study. Recruitment also includes both siblings and friends of those who took part in the original EPOCH study.

Description

Inclusion Criteria:

• Participant's parent or legal guardian gives consent and the participant, where age-appropriate, gives assent for participation in the study.
• Participant is male or female, aged 3-9 years at enrolment.
• Participant previously took part in the EPOCH study, or the participant's friend or sibling took part.

Exclusion Criteria:

• Evidence of congenital heart disease or significant chronic disease relevant to cardiovascular or metabolic status

For exclusion of MRI component only:

• Contraindication to MRI
• Unsuitable for MRI based on the responses to the MRI screening form

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac left ventricular mass	Echocardiography assessment of left ventricular mass indexed to body surface area (in g and g/m^2)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac right ventricular mass	Echocardiography assessment of right ventricular mass indexed to body surface area (in g and g/m^2)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac left ventricular end-diastolic volume	Echocardiography assessment of cardiac left ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac right ventricular end-diastolic volume	Echocardiography assessment of cardiac right ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac left ventricular systolic function	Echocardiography assessment of left ventricular systolic function: left ventricular ejection fraction (in %)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac right ventricular systolic function	Echocardiography assessment of right ventricular systolic function: tricuspid annular plane systolic excursion (in cm)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac left ventricular diastolic function	Echocardiography assessment of right ventricular (RV) diastolic function: RV Doppler early/late diastolic tricuspid inflow velocity ratio (E/A)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Cardiac right ventricular diastolic function	Echocardiography assessment of left ventricular (LV) diastolic function: LV Doppler early/late diastolic mitral inflow	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Morphology of the left ventricles	MRI assessment of the left ventricles morphology using cardiac statistical atlas and principal component analysis	6-9 years of age
Morphology of the right ventricles	MRI assessment of the right ventricles morphology using cardiac statistical atlas and principal component analysis	6-9 years of age
Cardiac flow dynamics of the left ventricle	MRI assessment of direct flow, delayed ejection flow, retained inflow, residual volume kinetic energy flow components at end diastole (measured at end diastole in mJ and overall % contribution)	6-9 years of age
Systolic blood pressure measurement	Resting brachial blood pressure measurement (in mmHg)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Diastolic blood pressure measurement	Resting brachial blood pressure measurement (in mmHg)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Mean arterial pressure	The average arterial pressure from resting brachial blood pressure measurement (in mmHg)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Retinal arteriolar structure	Central retinal arteriolar equivalent (CRAE in μm) measured using retinal imaging	6-9 years of age
Retinal venular structure	Central retinal venular equivalent (CRVE in μm) measured using retinal imaging	6-9 years of age
Retinal arteriolar-to-venular diameter ratio (AVR)	The ratio of average retinal arteriolar diameter (CRAE in μm) and average retinal venous diameter (CRVE in μm) measured using retinal imaging	6-9 years of age
Lung function	The forced expiratory volume in one second (FEV1 in L), forced vital capacity (FVC in L), and the ratio of FEV1 to FVC (FEV1/FVC) measured using spirometry	6-9 years of age
Objective measure of physical activity	The amount of moderate to vigorous physical activity (in h/week) and vigorous physical activity (in h/week) measured using wrist worn accelerometer	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Body weight	Body weight measured in kg	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Body height	Body weight measured in m	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Body mass index	Body weight divided by the square of height (in kg/m2)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Mid-arm circumference	Mid-arm circumference measured in cm	3-5 years of age OR 8-12 years of age; AND 6-9 years of age
Waist-to-hip ratio	The ratio of waist circumference (in cm) to hip circumference (in cm)	3-5 years of age OR 8-12 years of age; AND 6-9 years of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tube formation capacity in endothelial colony forming cells (ECFCs)	The number of closed tubes formed/1.5x10^4 cells	6-9 years of age
Endothelial colony forming cells (ECFC) branches formed	The number of branches formed/1.5x10^4 cells	6-9 years of age
Endothelial colony forming cells (ECFC) colony formation	Days for ECFC colony formation, measured in days	6-9 years of age
Endothelial colony forming cells (ECFC) proliferation rate	ECFC proliferation rate, measured as a percentage	6-9 years of age
Subcortical brain volume of hippocampus	Subcortical brain volume of hippocampus (in mm3) assessed on T1-weighted sequence of brain MRI	6-9 years of age
Subcortical brain volume of thalamus	Subcortical brain volume of thalamus (in mm3) assessed on T1-weighted sequence of brain MRI	6-9 years of age
White matter hyperintensities count	The number of white matter hyperintensities on T2-weighted sequence of brain MRI	6-9 years of age
White matter hyperintensities volume	Total volume of white matter hyperintensities (in mm3) assessed on T2-weighted sequence of brain MRI	6-9 years of age
Cerebral vessel lumen diameter	Cerebral vessel lumen diameter (in μm) assessed on the time-of-flight sequence of brain MRI	6-9 years of age
Cerebral vessel density	Cerebral vessel density (in mm3) assessed on the time-of-flight sequence of brain MRI	6-9 years of age
Cerebral vessel tortuosity	The ratio of cerebral vessel tortuosity assessed on the time-of-flight sequence of brain MRI	6-9 years of age
Whole brain grey matter perfusion or cerebral blood flow (CBF)	Whole brain grey matter perfusion/CBF (in ml/100g/min) assessed on arterial spin labelling of brain MRI	6-9 years of age
Arterial cerebral blood volume fraction	Arterial cerebral blood volume fraction (in %) assessed on arterial spin labelling of brain MRI	6-9 years of age

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Adam Lewandowski, DPhil, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2019
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): June 1, 2036

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: children; preterm; cardiac function
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 18/WM/0131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No