May 25, 2020

Findings show abnormal blood flow between COVID-19-positive mothers, babies in utero

A study examining placental pathology in COVID-19-positive pregnant women has found that relative to controls, COVID-19 placentas had a higher prevalence of decidual arteriopathy and other features of maternal vascular malperfusion (MVM), a pattern of injury the authors say reflects abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. The research was published in the American Journal of Clinical Pathology.

Investigators analysed the placentas of pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, and compared them to historical controls and women with placental evaluation for a history of melanoma. From March 18, 2020, until April 7, 2020, only women with moderate-to-severe symptoms of COVID-19 underwent testing, but after that, all women presenting to labor and delivery were universally tested.

Historical controls underwent singleton third-trimester delivery with clinically indicated placental pathology examination between January 1, 2011, and June 30, 2018. A nested cohort of patients with a history of melanoma was created from the historical controls based on the presence of the word "melanoma" in the clinical history section of their pathology report. The authors noted that no patient in the study period had placental metastases, so they may be considered a random sample of the delivering population. 

Sixteen placentas from patients with SARS-CoV-2 were examined, with 14 patients having delivered at term (37-40 weeks), 1 delivered at 34 weeks, and 1 represented a 16-week intrauterine fetal demise (IUFD), which was excluded from the statistical analysis. Four patients had COVID-19 infection diagnosed between 25-34 days prior to delivery, 2 were diagnosed 6 and 7 days prior to delivery, and the remaining 10 were diagnosed on presentation to labor and delivery. Ten of 16 patients were symptomatic, with 2 requiring oxygen, however no patients were intubated and there were no maternal deaths.

Features of MVM were observed in 12/15 cases, significantly higher than the melanoma control population (59/215, P = 0.001), as well as all controls (7,754/17,479, P = 0.046). Features included central (1/15) and peripheral (3/15) villous infarctions, villous agglutination (3/15), and accelerated villous maturation (2/15). Decidual arteriopathy was seen in 7/15 cases, including atherosis and fibrinoid necrosis of maternal vessels (3/15) and mural hypertrophy of membrane arterioles (5/15). The authors noted that only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia.

One COVID-19 case showed acute inflammatory pathology (AIP) including histologic chorioamnionitis and umbilical arteritis, corresponding to maternal and fetal inflammatory response stages of 2 and 2, respectively. The rate of AIP was significantly lower than both melanoma (114/215, P = 0.001) and all historical (9,879/17,479, P = 0.0003) controls. Two COVID-19 cases exhibited chronic inflammatory pathology (CIP), both with low-grade chronic lymphocytic villitis and chronic deciduitis with plasma cells, although these rates were not significantly different from melanoma (62/215, P = 0.246) or all historical (6,739/17,479, P = 0.082) controls.

Four of 15 placentas showed chorangiosis, which was increased relative to all historical controls (889/17,479, P = 0.001), as well as melanoma controls (11/215, P = 0.011). Two of the cases with chorangiosis were in asymptomatic women, while 1 was from a woman with 1 week of symptomatic COVID-19, and the fourth was from a woman who recovered from symptomatic COVID-19 diagnosed initially 34 days prior to delivery. The latter woman also had gestational diabetes, which the authors said complicated the interpretation of the findings.

Meanwhile, the 16-week IUFD case occurred in an asymptomatic woman who tested positive for SARS-CoV-2 at the time of admission to labor and delivery. Placental pathology in this case demonstrated retroplacental hematoma and villous edema. There was no acute or chronic inflammation noted.

"No pathognomonic features are identified" in the study, wrote Elisheva D Shanes, Feinberg School of Medicine, Northwestern University, Chicago, IL, and colleagues, but "there are increased rates of [MVM] features and intervillous thrombi, suggesting a common theme of abnormal maternal circulation, as well as an increased incidence of chorangiosis. These findings provide mechanistic insight into the observed epidemiologic associations between COVID-19 in pregnancy and adverse perinatal outcomes."

Further, as per hospital protocol, all live infants born to SARS-CoV-2 mothers were tested by a nasopharyngeal and throat swab at greater than 24 hours of life, a minimum of once and up to twice, for SARS-CoV-2, and none were positive. "This corroborates existing evidence that vertical transmission of the virus is uncommon and suggests that placental changes, if caused by COVID-19, are related to maternal infection and inflammation rather than fetal infection," the authors said.

They noted that the relatively low number of patients in the study limits the assessment of low frequency or variable outcomes. Moreover, the study does not formally test causality or the direct relationship between SARS-CoV-2 infection and development of placental pathology. "It is possible that viral infection directly leads to placental pathology or that there is a common underlying cause for both placental lesions and susceptibility to SARS-CoV-2," they added. 

SOURCE: American Journal of Clinical Pathology