Exploring retinal biomarkers as a novel predictor of pregnancy complications including stillbirth

Centre/Institute: Centre for Cardiovascular Science

Background

Every 16 seconds one baby is stillborn. That amounts to more than two million stillborn babies globally every year. Stillbirths have long-lasting personal and psychological consequences for parents and families, as well as substantial costs for wider society. Stillbirth is the endpoint of a number of different processes that involve the mother, baby, or the placenta – or a combination of the three. The lack of methods to assess gestational development in utero limits our ability to predict the risk of stillbirth. Today 25-50% of stillbirths are unexplained - meaning that no conditions that affect the mother, baby, or placenta that could contribute to the baby’s death are identified.

The eye provides a unique “window” to detect microvascular changes through analysis of images showing the retinal and choroidal microvascular networks. Increasing evidence supports structural and functional changes in retinal blood vessels as a biomarker for early identification of pathological conditions including neurodegenerative diseases, diabetes, renal disease and stroke. A handful of studies have reported changes in the retinal vasculature in association with pregnancy complications including pre-eclampsia and reduced fetal growth. This raises the exciting potential for retinal imaging in pregnancy to be used for early detection of pregnancy pathologies, allowing early preventative measures. Use of retinal imaging is attractive as it is non-invasive, quick to perform (<15 minutes) and can be done at scale, particularly with the emergence of portable hand held devices. However, during pregnancy there are dramatic changes to the circulation and vasculature. Little is known about the natural variation of the retinal vasculature across this short dynamic timeframe.

We have an ongoing research study ‘i-test’, in which we are collecting data and testing the utility of novel biomarkers derived from retinal imaging as an innovative, non-invasive predictor of maternal vascular responses to pregnancy and placental insufficiency. We aim to identify new retinal biomarkers for integration into models that are predictive of the risk of stillbirth. The proposed PhD project will have access to the i-test data and research team with the successful candidate contributing novel image and data analysis to the research efforts.

Aims

1. To analyse fundus and optical coherence tomography (OCT) images from pregnant women (n=200) participating in a longitudinal study in pregnancy:

   • To conduct vessel analysis using 2D infra-red fundus images of the retinal surface to characterise the microvascular system visualized therein with quantified measurements (mean/standard deviation) of vessel calibre, tortuosity, and network branching complexity.
   • To conduct complimentary analysis using OCT scanning to image retinal vessels cross-sectionally to measure vessel calibre and wall thickness, and compare to quantification derived from fundus imaging
   • To conduct choroidal analysis using 3D OCTimages including quantified measurements (mean/standard deviation) of thickness and volume of choroidal layer and segmentation of vessels and quantification (mean/standard deviation) of the choroidal vascular index.
2. To determine change in measurements over time (between 12 and 36 weeks gestation and between 20 and 36 weeks gestation.
3. To determine whether measurements differ between women with pregnancies complicated by fetal growth restriction and/or pre-eclampsia compared with healthy pregnancies and asses the predictive power.
4. Investigate whether the techniques developed/applied in Aim 1 can be adapted to work with emerging hand-held technologies for imaging the retina.

Training outcomes

Image analyses of retinal vessels and OCT using specialist image analysis software.

Statistical methods and analyses.

Understanding of research ethics and conduct of research in pregnancy.

Training in good clinical practice for research

Interdisciplinary team working.

Scientific writing of a review and 1^st author manuscripts.

Patient and public involvement and engagement.

References:

1.       Never forgotten: The situation of stillbirth around the globe. Report of the UN Inter-agency Group for Child Mortality Estimation, 2022. Available from https://data.unicef.org/resources/never-forgotten-stillbirth-estimates-report/ Accessed July 2023.

2.       Giarratano et al. utomated Segmentation of Optical Coherence Tomography Angiography Images: Benchmark Data and Clinically Relevant Metrics. Translational Vision Science & Technology. 2020;9(13):5.

3.       Ciloglu et al Optical coherence tomography angiography findings in preeclampsia. Eye 2019;33(12):1946-1951

4.       Li et al Associations of maternal retinal vasculature with subsequent fetal growth and birth size. PloS One 2015;10(4):e0118250