Feb. 11, 2022 – Women who become infected with COVID-19 during pregnancy face higher risks of still birth and death of a child within 28 days of birth, research has shown. And now, a new study shows how.

Unlike many disease-causing pathogens that kill the fetus by infecting it directly, the coronavirus causes "widespread and severe" destruction of the placenta that deprives the fetus of oxygen, a team of 44 researchers in 12 countries concluded after examining 64 stillbirths and four neonatal deaths in which the placenta was infected with the virus. They found that such damage occurs in a small percentage of pregnant women with COVID-19, and that all the women affected had not been vaccinated against the disease.

The findings were published online Thursday in the Archives of Pathology & Laboratory Medicine.

Nearly all placentas each had three features that pathologists call SARS-CoV-2 placentitis: large deposits of fibrin, a clotting protein that obstructs the flow of blood; death of cells in the trophoblast, which supplies the embryo with nourishment and later becomes part of the placenta; and an unusual form of inflammation called chronic histiocytic intervillositis.

The researchers called the extent of damage "striking," affecting 77.7% of the placenta on average. The virus did not appear to harm fetal tissue, but placental damage "was extensive and highly destructive," they write. Notably, none of the women in the analysis was known to have severe COVID-19.

Virus Seen "Chewing Up the Placenta"

David Schwartz, MD, a pathologist in Atlanta, and the lead author of the study, said COVID appears to be unique in destroying the placenta.

"I don't know of any infection that does that to this degree or with this uniformity," Schwartz says. "The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus."

The CDC reported in November that COVID-19 increases the risk of losing a pregnancy. From March 2020 to September 2021, 8,154 stillbirths were reported, affecting 0.65% of births by women without COVID and 1.26% of births by women with COVID-19.

Delta, the variant that dominated in mid-2021, appears to have been particularly harmful. The CDC reported that the relative risk for stillbirth for mothers with COVID-19 during that period increased to 4.04. Many cases in the new analysis coincided with Delta.

Schwartz and his colleagues say vaccines, along with antiviral therapy, might reduce the chance of the virus infecting the placenta. None of the mothers in the analysis was vaccinated, and Schwartz said he is not aware of a single case in a vaccinated woman.

The analysis comes after of a study from the National Institutes of Health that linked severe- to moderate-COVID-19 infection to greater risk of other pregnancy complications: Cesarean and premature delivery, death during childbirth, postpartum bleeding, and non-COVID infections.

Diana Bianchi, MD, director of NIH's National Institute of Child Health and Human Development, said those findings underscore the need for pregnant women to be vaccinated. (The shots have been shown to be safe for pregnant women.)

Denise Jamieson, MD, MPH, chair of the Department of Gynecology and Obstetrics at Emory University in Atlanta, who was not involved in the new analysis, says the findings may have important clinical implications.

Besides ensuring that pregnant patients are fully vaccinated, she said, doctors and health care providers could more closely monitor the placenta during pregnancy using tools like ultrasound.

Christopher Zahn, MD, vice president of practice activities with the American College of Obstetricians and Gynecologists, cautions that data on COVID-19 and pregnancy problems is limited.

The findings in this analysis "do not prove the association between COVID-19 infection and neonatal outcomes," Zahn said. "While stillbirth could potentially be another adverse outcome for pregnant people who contract COVID-19, currently we don't have enough data to confirm that a COVID-19 infection at any point in pregnancy indicates increased risk of stillbirth."