Mysterious Stillbirths May Be The Effect of Genetic Heart Desease

June 26, 2012

Genetic researchers have made an important step towards resolving the mystery of the causes of intrauterine fetal demise (IUFD), or stillbirth, where a baby dies in the womb after the 14th week of gestation. IUFD is responsible for 60% of perinatal mortality and occurs in about one in every two hundred pregnancies in Europe. Up to half of these stillbirths are unexplained. Now scientists from Italy, Germany, and the US have found that up to 8% of these unexplained deaths may be caused by specific genetic heart conditions.

Ms Alice Ghidoni, a PhD student at the University of Pavia, Italy, will tell the annual conference of the European Society of Human Genetics today (Tuesday) that the 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 causative 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 malignant arrhythmias could underlie some cases of IUFD as well,” she will explain. 

The researchers carried out molecular screening of stillborn fetuses where the cause of death remained unexplained after extensive post-mortem investigation. Informed consent was obtained from the parents. 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 1000 ethnically-matched controls.

Genetic testing is still quite rare in IUFD, but it is an important tool for uncovering the causes of unexplained death, says Ms Ghidoni. “The most common causes of fetal death are chromosomal abnormalities, infections, fetal-maternal hemorrhages, and maternal diseases”, she says. “Most of these are relatively easy to identify. Since genetic screening is a long, expensive and complicated procedure, currently it is not routinely performed in cases where an autopsy has not shown the cause of death. However, such molecular investigation could be very useful to identify specific genetic defects occurring in the family, so that future pregnancies can be monitored with close clinical follow-up. In some cases, life-saving treatment could be given.”

Identification of a fetus with a gene mutation for a cardiac channelopathy allows for treatment for the mother with drugs such as beta-blockers, the same treatment that is given to adults who have been identified with long QT syndrome.

Because the research was carried out by scientists from a number of different centers and countries, it was not possible to systematically collect parental DNA. However, as part of the planned expansion of the investigation, the researchers now intend 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.

“We have also identified new candidate genes which may be linked to cardiac channelopathies, and we will investigate them in our follow-up work,” says Ms Ghidoni. “Our current work shows that nearly 3% of IUFDs may be caused by a genetic variant with a cardiac disease-causing role, and another 5% by a variant that may predispose to disease. We believe that the new candidate genes may enlarge this field yet further. This is vitally important because we can then depict a clear picture of arrhythmic risk in perinatal life, both before and after birth.

“We believe that it is very important to increase knowledge of these genetic disorders among pediatric cardiologists and gynecologists and that genetic testing should be included in post-mortem analysis. 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,” Ms Ghidoni will conclude.

Source: redOrbit (http://s.tt/1fXdK)

Smallest and Largest Fetuses at Greater Risk of Being Stillborn, Research Finds

ScienceDaily (June 25, 2012) — The tiniest and the heaviest fetuses are at much higher risk of being stillborn than those of average weight, new research has found.

Fetuses who are "severely small for gestational age," or weigh below the bottom one percentile of all fetuses, disproportionately account for about six per cent of all stillbirths, according to researchers at St. Michael's Hospital.

Fetuses that are "severely large for gestational age," or weigh above the 99th percentile, account for nearly one per cent of stillbirths. "In this study of all registered liveborn and stillborn infants in Ontario, extreme underweight and overweight states confer the highest risk of stillbirth," said Drs. Joel Ray and Marcelo Urquia, authors of the paper that appears in the current issue of theJournal of Perinatology.

Stillbirth is traditionally defined as the death of a fetus at more than 23 weeks of gestation weighing 500 grams or more. However, Drs. Ray and Urquia included babies born starting as early as 20 weeks of gestation on the grounds that maternal-fetal bonding is well established at that point, since most mothers-to-be have undergone a Level 2 ultrasound detailing the unborn baby's developing bones and organs.

Including those babies provides new information about the degree to which low and high weights are associated with stillbirths, including those before the point of viability, Dr. Ray said. That, in turn, may help doctors better decide at which time point it is better to allow a pregnancy to continue so the fetus can grow, or to deliver a premature baby who might otherwise die in the womb.

The rate of stillbirths in industrialized countries is about six per 1,000, of which half occur after 27 weeks of gestation. In poorer countries, the rate is up to five times higher. Stillbirths are more common than the death of a baby after birth, such as from prematurity or as a result of Sudden Infant Death Syndrome. Yet, stillbirths have largely been ignored by our society, especially in terms of their emotional effect on the mother, her partner and extended family, Dr. Ray said.

The researchers examined records of all 767,016 live births and all 4,697 stillbirths in Ontario between 2002 and 2007. They said that because they looked at so many births, they could also make statistically precise estimations of the impact of extremely low birthweight on the risk of stillbirth.

They found that 19 per cent of stillbirths occur in fetuses under the tenth percentile of weight. But being below the first percentile of weight meant the fetus faced a 9.5 times higher risk of being stillborn than babies who are within the average weight range, between the 40th to 60th weight percentiles.

Dr. Ray said that when fetuses are severely small for gestational age, it usually means there is a problem with the placenta. Fetuses who are severely large for gestational age generally so because of the mom having diabetes or obesity.

The authors conclude that since more than 95 per cent of women in the industrialized world receive a Level 2 anatomical ultrasound before 22 weeks gestation, fetal weight should be estimated and reported at this time of the ultrasound, as a standard practice. In doing so, the early presence of a small or large fetus may help guide ongoing ultrasound surveillance for growth and well-being.

Story Source:

The above story is reprinted from materials provided by St. Michael's Hospital. The original article was written by Leslie Shepherd.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:
1.  J G Ray, M L Urquia. Risk of stillbirth at extremes of birth weight between 20 to 41 weeks gestation. Journal of Perinatology, 2012; DOI: 10.1038/jp.2012.60

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.