Cardiac defects associated with stillbirth
Research type
Research Study
Full title
The contribution of the cardiac conduction system development defects identified in the Erbb2 mouse model of embryonic death in unexplained stillbirth of human fetuses
IRAS ID
226043
Contact name
Alexander Heazell
Contact email
Sponsor organisation
Faculty of Biology, Medicine and Health, University of Manchester
Duration of Study in the UK
0 years, 3 months, 1 days
Research summary
Research Summary:
Each year around 2.6 million women experience the death of their unborn baby just before birth or during labour. This devastating end of pregnancy has an unknown cause in around half of the cases. The failure to explain the reason for the baby’s death increases the emotional burden on the affected families and also increases the cost on the health care providers.
This proposed project aims to address this problem through studying the association between developmental defects in the baby’s heart and unexplained fetal death in late pregnancy (unexplained stillbirth). To increase understanding, we have used a mouse which has abnormal heart function that leads to the death of mouse pups. Heart rhythm is normally controlled by proteins called cardiac ion channels. We have compared the cardiac ion channels between the abnormal and normal mice.
In this project we will assess these cardiac ion channels in human cases of unexplained stillbirth. We hope that this study will help us understand the link between abnormalities in heart function and unexplained fetal death in late pregnancy. This information would be a step forward towards identifying the underlying causes of the unexplained stillbirth. Identifying the correlation between abnormal heart function and unexplained stillbirth could allow the development of early tests and treatments to prevent this tragic end of pregnancy.Summary of Results:
: Although parents have investigations after a baby is stillborn (when a baby dies after 24 weeks of pregnancy but before birth) about 20% of stillbirths remain unexplained. Abnormal heart rhythms have been identified as a cause of death in Sudden Infant Death Syndrome (SIDS), also called cot death. It is possible that these could also be associated with unexplained stillbirths. Heart rhythm is controlled by special proteins in heart muscle called ion channels. This study aimed to understand if the amount or location of cardiac ion channels were altered in cases of unexplained stillbirths.
We use heart tissue from 20 cases of unexplained stillbirth and 20 cases of stillbirths from a shortage of oxygen in labour. We used staining techniques to look at the structure of heart muscle and electrical conduction system and five ion channels: CACNA1G, KCNJ2, KCNQ1, KCNH2 and KCNE1. We used software to measure the amount of staining in heart muscle.
The structure of heart muscle was altered in babies who died due to a shortage of oxygen but not in unexplained stillbirths. The amount of two ion channels CACNA1G and KCNJ2 had less staining in unexplained stillbirth groups, but there were no differences in KCNQ1, KCNH2 and KCNE1.
This study has shown that two ion channels associated abnormal heart rhythms were reduced in cases of unexplained stillbirth. Further genetic studies using human tissue should be performed to understand whether these play a role in otherwise unexplained stillbirths.REC name
East Midlands - Derby Research Ethics Committee
REC reference
17/EM/0362
Date of REC Opinion
19 Oct 2017
REC opinion
Further Information Favourable Opinion