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Genetic Research May Help Identify Causes of Stillbirth

HealthDay News
by -- Steven Reinberg
Updated: Aug 12th 2020

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WEDNESDAY, Aug. 12, 2020 (HealthDay News) -- Scientists are well on the way to understanding more about how genes can cause stillbirth, new research suggests.

In the study, researchers used genetic analyses to identify gene mutations that are linked to stillbirth, which is the in utero death of a fetus after 20 weeks' gestation. The findings might help doctors counsel parents who have experienced a stillbirth.

The team, led by David Goldstein and Dr. Ronald Wapner of Columbia University Vagelos College of Physicians and Surgeons in New York City, identified the likely genetic causes in about one of every 10 cases of stillbirth studied.

"This study shows that careful genetic analyses can often identify the precise genetic causes of stillbirth and demonstrates the importance of diagnostic sequencing in all cases of unexplained stillbirth," Goldstein said. "Of equal importance, the work highlights how little we currently understand about the biology of stillbirth and the role that genomic analysis can play in helping us understand it."

Stillbirth occurs in about one in 100 pregnancies and is 10 times more common than sudden infant death syndrome (SIDS).

In most cases, the cause of stillbirth is unknown. Some stillbirths have been linked to infections and preeclampsia. Up to 20% have been tied to easily detectable chromosome abnormalities.

"Unlike postnatal childhood conditions that are presumed to be strongly genetic, stillbirth had yet to be systematically analyzed with modern genome sequencing approaches," Goldstein said in a university news release.

Wapner said doctors too often have no explanation to offer parents who experience a stillbirth. "Not only are they devastated, they're often left to wonder if it's something they did wrong or if it might happen again," he said.

For the study, the researchers sequenced genes from 246 stillborn fetuses and used a new statistical analyses to identify key gene mutations.

The investigators found small changes in 13 genes that caused fetal death, six of which had not previously been tied to stillbirth.

Goldstein said, "Although these are small changes in only a single site in the genome, they are, in effect, genomic sledgehammers that either dramatically change or knock out essential genes and appear responsible on their own for fetal demise."

These small genetic changes explained nearly 9% of the stillbirths. Combined with other mutations, 18% of the stillbirths had a known genetic cause, according to the report.

"Interestingly, some of the changes we found in genes known to cause postnatal diseases and conditions appeared to have more profound effects than the mutations linked to postnatal disease," Goldstein said.

In the future, these findings might help guide clinical care, Wapner suggested.

"To a woman who's just had a stillbirth, specific knowledge about the cause is critical," Wapner said. "They often blame themselves and some decide not to have any more children."

If the stillbirth was caused by a genetic mutation that occurred in the fetus but not in the parents, the problem is not likely to happen in future pregnancies, he explained.

"That knowledge would change the way we would provide care, and facilitate closure and bereavement for families," Wapner said.

The researchers found that at least 5% of stillbirths might be explained by mutations in so-called intolerant genes -- ones not tied to any known disease.

"We're opening up new frontiers in biology and the more we understand about basic human development, the more we can potentially intervene," Goldstein said.

The findings were published online Aug. 12 in the New England Journal of Medicine.

More information

For more on stillbirth, head to the U.S. Centers for Disease Control and Prevention.