Newly published research is the first to show that stillbirth can be inherited and tends to be passed down through male members of the family. That risk preferentially comes from the mother鈥檚 or father鈥檚 male relatives鈥攖heir brothers, fathers, grandfathers, uncles, or male cousins. But the odds of a couple losing a baby to stillbirth are even greater when the condition comes from the father鈥檚 side of the family.
鈥淪tillbirth is one of those problems that is so tragic and life-changing,鈥 says Jessica Page, MD, an assistant professor in the Department of Obstetrics & Gynecology at 香蕉视频 of Utah Health and Intermountain Healthcare. 鈥淚t is especially frustrating when you don鈥檛 have a good answer for why it happens. This knowledge may give us the opportunity to change how we risk stratify people and reduce their risk through prevention.鈥
The results, published in , come from the largest study of its kind to examine the health histories of families over multiple generations. Page is co-author on the study led by , and senior author Robert Silver, MD, both of whom are faculty in the Department of Obstetrics & Gynecology at U of U Health.
鈥漇tudying pregnancy provides the opportunity to improve the health of future generations.鈥
鈥淪tudying pregnancy provides the opportunity to improve the health of future generations,鈥 Workalemahu explains. He says that understanding patterns of stillbirth in families may help genetic counselors advise their patients about their risk. It is also an important step toward identifying specific genes that increase the risk of stillbirth, which could one day lead to better diagnosis and prevention.
Searching for risks of stillbirth
In the U.S., stillbirth is more common than many people realize, occurring in 1 in 165 births among babies that are 20 weeks or older. The risk goes up when the mother has certain health conditions such as gestational hypertension, preeclampsia, or diabetes, but the causes of as many as 1 in 3 cases still go unexplained.
To understand other risk factors contributing to stillbirth, the scientists examined 9,404 stillbirth cases and 18,808 live birth controls between 1978 and 2019 that were represented in the Utah Population Database, a genealogical resource linked to health, birth, and death records. They found that 390 families had an excess number of stillbirths over multiple generations, suggesting there are genetic causes of stillbirth.
By comparing incidence of stillbirth among first-, second-, and third-degree relatives of babies from affected families with the equivalent relatives from unaffected families, the scientists identified familial risk in related individuals. Their analysis revealed that an increased risk for stillbirth was passed down through male family members, a trend that had not been seen before.
鈥淲e were able to evaluate multigenerational trends in fetal death as well as maternal and paternal lineages to increase our ability to detect a familial aggregation of stillbirth,鈥 Workalemahu says. 鈥淣ot many studies have examined inherited genetic risk for stillbirth because of a lack of data. The Utah Population Database (UPDB) allows for a more rigorous evaluation than has been possible in the past.鈥
The population in the UPDB has similar genetic diversity to the U.S. population of northern European descent and may not be generalizable to the general U.S. population. Future studies will need to determine whether the trends hold true among people of different races and ethnicities.
鈥淪tillbirth rate reduction has been slow in the U.S. and we think many stillbirths may be potentially preventable,鈥 Page says. 鈥淭his is motivating us to look for those genetic factors so we can achieve more dramatic rate reduction.鈥
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The research published as, 鈥溾 and is supported by grants from the National Institutes of Health.
In addition to U of U Health, collaborating institutions are Intermountain Healthcare, 香蕉视频 of Washington, Rutgers, and the National Institutes of Health.