New research by University of Utah Health is the first to show that stillbirth risk is passed down genetically through male members of the family.

Published last week in BJOG, an international journal of obstetrics and gynecology, the research shows the risk of stillbirth preferentially comes from the mother’s or father’s male relatives, including their brothers, fathers, grandfathers, uncles or male cousins. However, the odds of stillbirth are even higher if the condition comes from the father’s side of the family.

“Stillbirth is one of those problems that is so tragic and life-changing,” said Dr. Jessica Page, in a press release. Page is assistant professor in the Department of Obstetrics & Gynecology at University of Utah Health and Intermountain Healthcare and co-author of the study. “It is especially frustrating when you don’t 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.”

The study was led by Tsegaselassie Workalemahu and Dr. Robert Silver, the senior author. Both are faculty members in the Department of Obstetrics & Gynecology at U of U Health.

According to the study, stillbirth in the United States occurs in 1 in 165 births among babies 20 weeks or older. The risk increases when the mother has certain health conditions such as gestational hypertension, preeclampsia, or diabetes. The causes of as many as 1 in 3 cases still go unexplained.

“Studying pregnancy provides the opportunity to improve the health of future generations,” Workalemahu said. “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.”

During the study, researchers examined 9,404 stillbirths and 18,808 live births represented in the Utah Population Database between 1978 and 2019. The database is a genealogical resource linked to health, birth and death records. Researchers found 390 families reporting an excess number of stillbirths over multiple generations, suggesting a genetic cause — a trend that has not been identified before.

“We 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,” said Workalemahu. “Not many studies have examined inherited genetic risk for stillbirth because of a lack of data. The Utah Population Database allows for a more rigorous evaluation than has been possible in the past.”

The database has similar genetic diversity to the U.S. population of northern European descent, but may not be generalizable to the general U.S. population, according to the study. Future studies will be needed to determine whether the trends hold true among people of different races and ethnicities.

“Stillbirth rate reduction has been slow in the U.S. and we think many stillbirths may be potentially preventable,” Page said. “This is motivating us to look for those genetic factors so we can achieve more dramatic rate reduction.”

The research was supported by grants from the National Institutes of Health and U of U Health. Collaborating institutions are NIH, Intermountain Healthcare, University of Washington and Rutgers.

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