UK cohort study of congenital anomalies potentially requiring surgery in children (Surgical-PEARL study)

ISRCTN	ISRCTN12557586
DOI	https://doi.org/10.1186/ISRCTN12557586
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	302251
Protocol serial number	2021-4859, IRAS 302251, CPMS 51673
Sponsor	University of Bristol
Funders	Oyster Foundation Charity, British Heart Foundation, NIHR Bristol Biomedical Research Centre

Submission date: 26/04/2022
Registration date: 28/04/2022
Last edited: 19/03/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Genetic Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Around 1 in 60 babies are born with congenital anomalies (a structural condition) that require surgery to survive but we don’t really know why congenital anomalies occur. We are setting up a study to collect information about the health and quality of life of children with congenital anomalies that may require surgery. We are asking parents whose unborn baby or child has been diagnosed with a structural condition to take part in this study. We hope to look at risk factors by collecting samples from children and their parents. By monitoring children’s blood, urine and stool during their care in the hospital we may be able to work out better treatments for them.

Who can participate?
Children ages 0-5 years old, diagnosed with a congenital anomaly that might require surgery to correct.
The study will also invite the biological parents to collect data and samples.

What does the study involve?
Participants can be approached before or after birth. Once the congenital anomaly has been diagnosed, the parents will be approached by the study team and given a participant information leaflet. If the parents consent to their child taking part in the study, details about their delivery and surgery will be collected by the research team. If the parents also consent to samples, these will be collected after delivery (placenta, umbilical cord blood), where applicable, and during their surgical admission (blood, urine, stool and waste tissue). Parents will also be asked to complete a questionnaire 12, 24, 36 and 48 months after delivery. Questionnaires will be completed online and include questions about risk factors, their quality of life and if they have been admitted to the hospital or seen a GP since their surgery.
Biological parents will also be approached and given a participant information leaflet. If they are happy to take part in the study, data on potential risk factors will be collected from medical notes and/or questionnaires, and blood and urine samples will be collected.

What are the possible benefits and risks of participating?
There are no direct benefits of participating in the study, but we hope that the results from this study may benefit future care and outcomes for patients and the NHS. Samples will be taken from the children from lines that are already in place, so no extra needles will be needed.
There is very minimal risk associated with taking blood samples from the biological parents.

Where is the study run from?
The study is run from the University of Bristol and will take place in hospitals around the UK.

When is the study starting and how long is it expected to run for?
April 2021 to January 2032

Who is funding the study?
The study is currently funded by the Oyster Foundation Charity, the British Heart Foundation and the Bristol Biomedical Research Centre (UK).

Who is the main contact?
Clare Skerritt, clare.skerritt@uhbw.nhs.uk
Emma Griffiths, emma.griffiths@uhbw.nhs.uk
Mai Baquedano, pearl-study@bristol.ac.uk

Contact information

Miss Clare Skerritt
Principal investigator

Bristol Royal Hospital for Children
Upper Maudlin Street
Bristol
BS2 8TP
United Kingdom

ORCID ID	0000-0002-2461-4344
Phone	+44 1173428839
Email	clare.skerritt@uhbw.nhs.uk

Ms Mai Baquedano
Public

Level 7, Queens Building
Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

ORCID ID	0000-0002-7101-3082
Email	pearl-study@bristol.ac.uk

Mr Stuart Mires
Scientific

University of Bristol
St Michael’s Hospital
Southwell Street
Bristol
BS2 8EG
United Kingdom

ORCID ID	0000-0002-1810-8672
Phone	+44 117 342 5470
Email	stuart.mires@bristol.ac.uk

Dr Emma Griffiths
Scientific

St Michael’s Hospital
Southwell Street
Bristol
BS2 8EG
United Kingdom

ORCID ID	0000-0002-4180-2224
Email	Emma.Griffiths@uhbw.nhs.uk

Study information

Primary study design	Observational
Study design	Multi-centre prospective cohort study
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	Surgical Paediatric congEnital Anomalies Registry with Long term follow-up (Surgical-PEARL study)
Study acronym	Surgical-PEARL
Study objectives	Congenital anomalies or rare diseases affect 1 in 64 live births. Those with structural anomalies often require surgical interventions to survive. The potential causes of congenital anomalies potentially requiring surgical interventions (CAPRS) and the factors influencing their prognosis are not well understood. It is likely that they occur as a result of interacting molecular, genetic and environmental risk factors. This study aims to create a data registry tracking CAPRS from diagnosis through to long term outcomes including routinely collected clinical data on interventions and survival, as well as collecting biological samples from patients and their biological parents.
Ethics approval(s)	Approved 15/03/2022, South East Scotland Research Ethics Committee 01 (2nd Floor, Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, UK: +44 131 536 9000; Sandra.Wyllie@nhslothian.scot.nhs.uk), ref: 22/SS/0004
Health condition(s) or problem(s) studied	Congenital anomalies potentially requiring surgical intervention
Intervention	Participants can be recruited antenatally or postnatally. Once the congenital anomaly has been diagnosed, the parents will be approached and given a Participant Information Leaflet. When a parent consents to their child taking part, data from their delivery and surgical admission will be collected. Where parents have also consented to samples, placenta and umbilical cord samples will be collected after delivery (if patient has been approached antenatally) and blood, urine, stool and waste tissue will be collected during their surgical admission. These samples are stored for future analyses to identify potential markers of post-operative complications and recovery. Parents will also be asked to complete a questionnaire on behalf of the children 12, 24, 36 and 48 months after delivery or surgery. Questionnaires will be completed online and include questions about risk factors, quality of life (PEDSQL) and resource use. Participants also consent for details to be collected from NHS Digital and other clinical databases. Patient involvement in the study finishes once all questionnaires have been submitted. Biological parents will also be invited to take part in the study to provide data and samples. If the parents consent, blood and urine samples will be taken and they will be asked to complete a questionnaire on potential risk factors during pregnancy. Where consent has been obtained, pseudonymised samples may be made available to future Research Ethics Committee (REC) approved studies.
Intervention type	Other
Primary outcome measure(s)	1. Aggregated routinely collected clinical data from review of medical notes: operation details, PICU/NICU, HeartSuite, Hospital episode statistics (HES), HER, Magnetic Resonance Imaging (MRI), Computerised tomography (CT), Echocardiogram (ECHO), ultrasounds. Assessed at baseline and then yearly for 5 years. 2. Phenotypic and genetic analysis of biomaterials that would normally be discarded during surgery as well as blood, urine and stool samples from patients and their biological parents. Biological mothers will provide baseline blood and urine samples, and optional amniotic fluid sample (if patient is recruited antenatally). Biological fathers will provide baseline blood and urine samples. Patients will provide pre-operative blood, urine, stool and tissue when available, on arrival to PICU: blood and urine samples, 24 hours post-surgery: blood and urine samples.
Key secondary outcome measure(s)	1. Demographics collected via questionnaires at baseline 2. Maternal and paternal demographics and information on potentially modifiable risk factors associated with CAPRS, assessed using questionnaires developed specifically for this study and accessing relevant pregnancy medical records at baseline. 3. Short, medium and long-term clinical outcomes in patients born with CAPRS, monitored by reviewing the patient’s medical notes yearly for 5 years. 4. NHS resource use, monitored by reviewing the patient’s medical notes yearly for 5 years and using questionnaires developed specifically for this study 5. Patient’s and parents’ quality of Life (QoL) measured using PEDSQL questionnaires 12, 24, 36 and 48 months post-delivery (for patients recruited antenatally) or post-consent (for patients recruited postnatally). 6. Genetic and phenotypical characterisation of patients and their mothers and fathers. 7. MicroRNA analyses and isolation of progenitor cells when sufficient tissue, plasma and serum are available
Completion date	16/01/2032

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	0 Months
Upper age limit	5 Years
Sex	All
Target sample size at registration	2500
Key inclusion criteria	Patients must be: 1. Fetus (2nd and 3rd trimester) or aged between 0 months and 5 years of age 2. Diagnosed with CAPRS The person giving consent must: 3. Have parental responsibility for the participant Biological mothers and fathers: 4. Have a biological child enrolled in PEARL 5. Have capacity to consent
Key exclusion criteria	1. Unable to give informed consent and/or assent 2. Main residence is outside the UK
Date of first enrolment	19/05/2022
Date of final enrolment	01/01/2032

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University Hospitals Bristol and Weston NHS Foundation Trust

Trust Headquarters
Marlborough Street
Bristol
BS1 3NU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from pearl-study@bristol.ac.uk.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		09/12/2022	06/01/2023	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

19/03/2025: Contact details updated.
12/02/2024: Contact details updated.
06/01/2023: Publication reference added.
24/05/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/05/2022 to 19/05/2022.
2. The individual participant data (IPD) sharing statement has been added and the IPD sharing summary has been changed from "Data sharing statement to be made available at a later date" to "Available on request".
05/05/2022: Internal review.
26/04/2022: Trial's existence confirmed by NHS Lothian