Can eye imaging in pregnancy help predict stillbirth?
| ISRCTN | ISRCTN40843826 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40843826 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 332944 |
| Protocol serial number | AC23144, CPMS 60001 |
| Sponsor | Accord (United Kingdom) |
| Funders | Wellcome Leap, Rosetrees Trust |
- Submission date
- 28/09/2025
- Registration date
- 29/09/2025
- Last edited
- 03/10/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
This study aims to further our understanding of why some babies are stillborn and help us identify new tests that we can offer people in pregnancy to identify babies that might be at risk. Every year, around the world, more than two million babies are stillborn and in many of these cases no clear cause is identified. Our current monitoring looks at pregnant women and babies’ health using blood tests, blood pressure and ultrasound scans during pregnancy but we know this does not provide a complete picture.
In pregnancy there are changes in the structure and function of blood vessels throughout the body. These blood vessel changes may lead to complications such as pre-eclampsia, high blood pressure and stillbirth. Looking at what is happening to the blood vessels at the back of the eye can help us know what is happening to blood vessels in the rest of the body. This is a simple, quick and non-invasive test that you may have previously had during a visit to the optician.
The purpose of the study is to find out whether monitoring changes in the eye’s blood vessels during pregnancy could be a new way of identifying those at risk of pregnancy complications.
Who can participate?
Pregnant women living in the Lothian area who are aged between 16 and 50 years, and who are pregnant with a single baby, are eligible to take part.
What does the study involve?
Participants will be invited to study visits at one (at around 36 weeks) or two (at around 12 or 20 weeks, and at 36 weeks) timepoints during pregnancy. At these visits, pictures of the backs of each eye will be taken using a specialised camera.
At the 36-week visit, an ultrasound scan will also be carried out to look at the womb, placenta, and baby. A blood test will also be taken at the 36-week visit.
Participants will be invited to one follow-up visit 6-18 months after the birth of their baby. At this visit, further pictures of the backs of the eyes will be taken, as well as non-invasive measurements of the heart and blood vessels, and further samples of blood and urine.
What are the possible benefits and risks of participating?
There will be no direct benefits from taking part in the study, but the results may help to improve the healthcare of pregnant women in the future. None of the measurements taken are expected to pose any risks to the health of participants or their pregnancies. However, there may be inconvenience associated with having to take time to travel to and attend study visits. The blood tests can sometimes cause minor bruising.
There is a small possibility that the measurements may reveal a health problem that a participant was unaware of. In the unlikely scenario that this does occur, the participant will be referred to receive further medical advice and treatment as appropriate.
Where is the study run from?
The University of Edinburgh (UK)
When is the study starting and how long is it expected to run for?
April 2023 to April 2027
Who is funding the study?
1. Wellcome Leap
2. Rosetrees
Who is the main contact?
Prof. Rebecca Reynolds, R.Reynolds@ed.ac.uk
Contact information
Public, Scientific, Principal investigator
Centre for Cardiovascular Science
Queens Medical Research Institute
Edinburgh BioQuarter
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
 ORCID ID |
0000-0001-6226-8270 |
|---|---|
| Phone | +44 (0)131 242 6762 |
| R.Reynolds@ed.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Single-centre observational study with two arms |
| Secondary study design | Longitudinal study |
| Participant information sheet | 48082_PIS_V4.0_ cross sectional cohort.pdf |
| Scientific title | I-TEST: Novel Biomarkers in Pregnancy for Early Prediction of Stillbirth |
| Study acronym | I-TEST |
| Study objectives | The aim of this study is to assess variability in features of the retinal vasculature during pregnancy between individuals and to describe their longitudinal trajectories over gestation and in the postpartum period. We aim to assess differences in retinal features and their trajectories between women with healthy pregnancies and those affected by placental dysfunction, in order to identify novel retinal biomarkers for integration into models that are predictive of the risk of stillbirth and future maternal cardiovascular disease. |
| Ethics approval(s) |
Approved 14/11/2023, London - Brighton & Sussex Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8140; brightonandsussex.rec@hra.nhs.uk), ref: 23/PR/1187 |
| Health condition(s) or problem(s) studied | Stillbirth and pregnancy complications linked to stillbirth risk (pre-eclampsia and fetal growth restriction) |
| Intervention | This is a single-centre observational study with two parallel cohorts as follows: 1. A longitudinal cohort with serial multimodal retinal imaging at 12 (+/-3) and 36 (+/-3) weeks, or at 20 (+/-3) and 36 (+/-3) weeks, in unselected pregnancies (cohort 1). 2. A cross-sectional cohort with multimodal retinal imaging in late pregnancy obtained at 36 (+/-3) weeks, in a cohort enriched with higher risk pregnancies (cohort 2). Participants from both cohorts will be invited to a single follow-up visit at 12 (+/-6) months postpartum, for repeat retinal imaging and cardiovascular assessment. Multimodal retinal imaging will be carried out at each study timepoint for both cohorts, comprising colour fundus photography, scanning laser ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography. In addition, at the 36-week study visit for both cohorts, supplementary maternal ultrasound assessments may be carried out including measurements of maternal and fetal Doppler indices and capture of research images of the placenta and fetus. Blood samples will also be collected at this 36-weeks appointment, and stored for future measurement of biomarkers of placental dysfunction, maternal vascular dysfunction, and stillbirth. Key maternal demographics and maternal and neonatal outcomes for all participants will be collected at birth from the electronic health record. The 12-month follow up study visit will comprise multimodal retinal imaging as described above, maternal cardiovascular assessment (including verbal report of smoking status and family history of cardiovascular disease, echocardiography, and measurement of height, weight, blood pressure, pulse wave velocity, and 24-hour ambulatory blood pressure and arterial stiffness). We will collect and store postnatal blood samples for measurement of biomarkers of cardiovascular dysfunction and urine samples for analysis of proteinuria (albumin-creatinine ratio) and storage for measurement of other potential biomarkers of cardiovascular dysfunction. In addition, we will seek consent from participants to collect outcome data on cardiovascular risk factors (including hypertension, diabetes, dyslipidaemia) and future cardiovascular events through lifelong data linkage to GP and hospital records. |
| Intervention type | Other |
| Primary outcome measure(s) |
1. Multimodal retinal imaging (colour fundus photography, scanning laser ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography) will be carried out at 36 weeks gestation and 12 months postpartum (cohort 1), or at 12 or 20 weeks gestation, 36 weeks gestation, and 12 months postpartum (cohort 2). Automated analysis of retinal images at all timepoints will be carried out to generate retinal vascular metrics including: |
| Key secondary outcome measure(s) |
1. Supplementary maternal ultrasound assessment will be carried out at 36 weeks' gestation for participants in both cohorts, and will include measurement of bilateral uterine artery Doppler, umbilical artery Dopplers, fetal middle cerebral artery Doppler, and capture of B-mode cross-sectional images of the placenta, fetal thorax, and fetal liver. |
| Completion date | 01/04/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Upper age limit | 50 Years |
| Sex | Female |
| Target sample size at registration | 650 |
| Key inclusion criteria | 1. Age 16-50 years 2. Able to give informed consent 3. Singleton pregnancy 4. 12 (+/- 3) weeks gestation or 20 (+ / - 3) weeks gestation (cohort 1) 5. >23 weeks gestation (cohort 2) 6. Living in Lothian area |
| Key exclusion criteria | 1. Women who are not pregnant 2. Women aged under 16 years or over 50 years 3. Women who are classified as Adults with Incapacity (AWI) as determined by midwife, GP or research team 4. Multiple pregnancy |
| Date of first enrolment | 01/12/2023 |
| Date of final enrolment | 01/04/2026 |
Locations
Countries of recruitment
- United Kingdom
- Scotland
Study participating centre
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in non-publicly available repository |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository (University of Edinburgh DataStore). This is a prospective study, and therefore informed participant consent will include provision for data sharing to maximise the value of the dataset for wider research use. The fully anonymised dataset will be available on study close-down with metadata documentation to enable understanding and reuse, upon request from Prof. Rebecca Reynolds (R.Reynolds@ed.ac.uk). All data users will be required to agree to a set of terms for the use of the data, in writing, prior to receipt of the data. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 4.0 | 29/09/2025 | No | Yes | |
| Participant information sheet | version 4.0 | 29/09/2025 | No | Yes | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 4.0 | 09/12/2024 | 29/09/2025 | No | No |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- 48082_PROTOCOL_V4.0.pdf
- Protocol file
- 48082_PIS_V4.0_ cross sectional cohort.pdf
- Participant information sheet
- 48082_PIS_V4.0_longitudinal cohort .pdf
- Participant information sheet
Editorial Notes
03/10/2025: Internal review.
29/09/2025: Study's existence confirmed by the London - Brighton & Sussex Research Ethics Committee.
