Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.
Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.
Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.
The research was published in the.
Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”
To learn more, Dr. Goldstein, lead author, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.
A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.
The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).
Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.
In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.
Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”
There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.
The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.
Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”
One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,”, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.
“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”
Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.
SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. .