B3982 - Maternal metabolic risk factors and prognosticators for offspring affected by congenital heart disease - 07/02/2022

B number: 
B3982
Principal applicant name: 
Massimo Caputo | University of Bristol
Co-applicants: 
Dr Stuart Mires, Dr Clare Skerritt
Title of project: 
Maternal metabolic risk factors and prognosticators for offspring affected by congenital heart disease.
Proposal summary: 

Congenital anomalies complicate over 2% of births, with congenital heart disease (CHD) the most common accounting for approximately one third. However, understanding of potential causes is limited, with only 20% related to known genetic, chromosomal or teratogenic factors. Greater knowledge of maternal risk factors and causative mechanisms is essential. Assessing the maternal metabolome offers an opportunity to achieve these goals. Metabolomics describes the study of small molecules and substances created by the processes of the body. It reflects how the body functions and is influenced by genetics, our environment and other factors such as health conditions and pregnancy. This project will perform large scale metabolomic analysis utilising the Children-OMACp, ALSPAC and Surgical-PEARL cohort studies based in the South-West of England. Firstly, case control study will compare metabolomic profiles of non-pregnant mothers of children with CHD to controls with no congenital anomaly. Further study will then compare metabolomic profiles in pregnant mothers of fetuses with CHD and controls with no congenital anomaly. This research aims to elucidate potential maternal metabolic risk factors and causative pathways for fetal CHD. It will also allow us to greater understand the role the fetus has in influencing maternal metabolomic profiles in pregnancies complicated by CHD. This can be compared to underlying maternal metabolic variation that could represent a causative pathway for fetal CHD. This understanding could revolutionise care for women before and during pregnancy. Furthermore, it offers an exciting opportunity for primary prevention of CHD.

Impact of research: 
It is clear that our understanding of maternal causal risk factors and mechanisms for fetal CHD is limited. The assessment of the maternal metabolome provides the opportunity to change this. This project will perform metabolomic assessment of both non-pregnant and pregnant mothers of children with CHD to identify potentially causative metabolic profiles and pathways. This will reduce the physical and psychological burden on children, families and societies as well as benefiting the NHS. Furthermore, it will improve opportunities for pre-conception counselling, optimising peri-conceptual care. The ultimate goal through greater understanding of causative mechanisms and pathways would be to develop pre- and peri- conceptual management strategies and treatments that could act in the primary prevention of CHD.
Date proposal received: 
Wednesday, 26 January, 2022
Date proposal approved: 
Monday, 31 January, 2022
Keywords: 
Epidemiology, Congenital abnormalities, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Mass spectrometry, Metabolomics, Biological samples -e.g. blood, cell lines, saliva, etc., Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, Cardiovascular, Mothers - maternal age, menopause, obstetrics, Metabolic - metabolism