European scientists move closer to solving stillbirth mystery
Researchers from Europe and the United States have made an important step towards resolving the mystery of stillbirth, an Italian researcher announced on Tuesday.
Intrauterine foetal demise (IUFD), or stillbirth, where a baby dies in the womb after the 14th week of pregnancy is responsible for 60% of perinatal mortality and occurs in about 1 in every 200 pregnancies in Europe. Around half of these stillbirths are unexplained, but scientists from Germany, Italy and the United States believe that up to 8% of these deaths may be caused by specific genetic heart conditions.
Ms Alice Ghidoni, a PhD student at the University of Pavia, Italy told participants at the annual conference of the European Society of Human Genetics (ESHG) that her group's research shows for the first time that cardiac channelopathies, hereditary diseases in which the heartbeat rhythm is disturbed, were likely to have played a role in some IUFD deaths.
'Since we knew that 10-15% of sudden infant death syndrome cases carry genetic variants associated with long QT syndrome or Brugada syndrome, we decided to investigate whether sudden death due to disorders of the heart rate could underlie some cases of IUFD as well,' she explained. Long QT and Brugada syndromes are conditions whereby an irregular heartbeat leads to sudden death and are best known for causing sudden unexplained death in young adults.
To test this theory, the researchers carried out molecular screening of stillborn foetuses where the cause of death remained unexplained after extensive post-mortem investigation. They looked for mutations of three genes, two of them involved in long QT and one in both long QT and Brugada syndromes, and found three disease-causing variants that were present in the IUFD cases, but absent in more than 1,000 ethnically-matched controls.
'The most common causes of foetal death are chromosomal abnormalities, infections, foetal-maternal haemorrhages and maternal diseases,' said Ms Ghidoni, which are generally 'relatively easy to identify.' However, 'since genetic screening is a long, expensive and complicated procedure, it is not routinely performed in cases where an autopsy has not shown the cause of death,' said Ms Ghidoni. She suggested that 'such molecular investigation could be very useful to identify specific genetic defects occurring in families, so that future pregnancies can be monitored with close clinical follow-up. In some cases, life-saving treatment could be given.' For example, if a foetus is found to have a gene mutation that would cause cardiac channelopathy, the mother can be treated with drugs such as beta-blockers, in the same way that adults who have been identified with long QT syndrome would be treated.
Because the research was carried out by scientists from a number of different centres and countries, it was not possible to systematically collect parental DNA. The researchers now intend, therefore, to enlarge the study population further and to collect DNA from all family members. Cardiac channelopathies run in families, so genetic testing will be able to identify not just those parents who are at risk of an affected pregnancy, but also all family members who may be unaware that they have a potentially fatal heart condition, said the researchers.
'We believe that it is very important to increase knowledge of these genetic disorders among paediatric cardiologists and gynaecologists and that genetic testing should be included in post-mortem analysis,' said Ms Ghidoni. 'Many more lives can be saved if there is sufficient awareness of these devastating conditions among healthcare professionals, as well as among the affected families who in many cases have already suffered enough.'
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Information Source: European Society of Human Genetics (ESHG)
Document Reference: Based on information from the annual conference of the European Society of Human Genetics