Recent evidence has shown women who contract COVID-19 during pregnancy are at increased risk for pregnancy loss and neonatal death. Now, an analysis of pathology data from dozens of perinatal deaths shows how.
Unlike numerous pathogens that kill the fetus by infecting it directly, SARS-CoV-2 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 placentas were infected with the virus. They noted that such damage occurs in a small percentage of pregnant women with COVID, and that all the women in the study had not been vaccinated against the disease.
The findings were published online today in the Archives of Pathology & Laboratory Medicine.
Nearly all placentas had each of three features that pathologists have dubbed SARS-CoV-2 placentitis: large deposits of fibrin, a clotting protein that obstructs the flow of blood; death of cells in the trophoblast; and an unusual form of inflammation called chronic histiocytic intervillositis. Some had other abnormalities that could have exacerbated the condition.
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.
Virus Seen “Chewing Up the Placenta”
David Schwartz, MD, a pathologist in Atlanta, Georgia, 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 told Medscape Medical News. “The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus.”
The Centers for Disease Control and Prevention reported in November that maternal COVID increases the risk of losing a pregnancy. From March 2020 to September 2021, 8154 stillbirths were reported, affecting 0.65% of births by women without COVID and 1.26% of births by women with COVID, for a relative risk of 1.90 (95% CI, 1.69 – 2.15).
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 (95% CI, 3.28 – 4.97). Many cases in the new analysis coincided with Delta.
Schwartz and his colleagues said immunization, along with antiviral therapy, might reduce the chance of SARS-CoV-2 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 on the heels of a study from the National Institutes of Health linking severe to moderate COVID infection to greater risk of other pregnancy complications: cesarean and preterm delivery, death during childbirth, postpartum hemorrhaging, and non-COVID infections.
Diana Bianchi, MD, director of NIH’s Eunice Kennedy Shriver 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, Atlanta, who was not involved in the new analysis, said the findings may have important clinical implications. In addition to ensuring that pregnant patients are fully vaccinated, she said, “There may be opportunities to more closely monitor the placenta during pregnancy using imaging modalities such as ultrasound.”
Even in the presence of severe abnormalities, a fetus that has reached a viable gestational age could potentially be delivered prior to stillbirth, Jamieson said. The 64 stillbirths in the analysis ranged from 15 to 39.2 weeks of gestation, with an average of 30 weeks. Eight were delivered at full term.
However, additional studies are needed to support monitoring of placental changes, she said: “It is not ready for prime time now.”
Christopher Zahn, MD, vice president of practice activities the American College of Obstetricians and Gynecologists, cautioned that data on COVID and pregnancy complications remain 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.”
He added that ACOG continues to strongly recommend vaccination against COVID for women who are pregnant, recently pregnant, or planning to be pregnant.
Schwartz and Jamieson have disclosed no relevant financial relationships. One author reported receiving financial support from the Slovak Research and Development Agency. Another reported funding from the Belgian Fund for Scientific Research and the Fetus for Life charity.
Arch Pathol Lab Med. Published online February 10, 2022. Abstract
Mary Chris Jaklevic is a healthcare journalist based in the Midwest.