Coronavirus disease 2019 infection and placental histopathology in women delivering at term

Abstract

Background: There is a paucity of data describing the effects of coronavirus disease 2019 on placental pathology, especially in asymptomatic patients. Although the pathophysiology of coronavirus disease 2019 is not completely understood, there is emerging evidence that it causes a severe systemic inflammatory response and results in a hypercoagulable state with widespread microthrombi. We hypothesized that it is plausible that a similar disease process may occur in the fetal-maternal unit.

Objective: This study aimed to determine whether coronavirus disease 2019 in term patients admitted to labor and delivery, including women without coronavirus disease 2019 symptomatology, is associated with increased placental injury compared with a cohort of coronavirus disease 2019-negative controls.

Study design: This was a retrospective cohort study performed at NYU Winthrop Hospital between March 31, 2020, and June 17, 2020. During the study period, all women admitted to labor and delivery were routinely tested for severe acute respiratory syndrome coronavirus 2 regardless of symptomatology. The placental histopathologic findings of patients with coronavirus disease 2019 (n=77) who delivered a singleton gestation at term were compared with a control group of term patients without coronavirus disease 2019 (n=56). Controls were excluded if they had obstetrical or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy, or thrombophilia. Multivariable logistic regression models were performed for variables that were significant (P<.05) in univariable analyses. A subgroup analysis was also performed comparing asymptomatic coronavirus disease 2019 cases with negative controls.

Results: In univariable analyses, coronavirus disease 2019 cases were more likely to have evidence of fetal vascular malperfusion, that is, presence of avascular villi and mural fibrin deposition (32.5% [25/77] vs 3.6% [2/56], P<.0001) and villitis of unknown etiology (20.8% [16/77] vs 7.1% [4/56], P=.030). These findings persisted in a subgroup analysis of asymptomatic coronavirus disease 2019 cases compared with coronavirus disease 2019-negative controls. In a multivariable model adjusting for maternal age, race and ethnicity, mode of delivery, preeclampsia, fetal growth restriction, and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the coronavirus disease 2019 group (odds ratio, 12.63; 95% confidence interval, 2.40-66.40). Although the frequency of villitis of unknown etiology was more than double in coronavirus disease 2019 cases compared with controls, this did not reach statistical significance in a similar multivariable model (odds ratio, 2.11; 95% confidence interval, 0.50-8.97). All neonates of mothers with coronavirus disease 2019 tested negative for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction.

Conclusion: Despite the fact that all neonates born to mothers with coronavirus disease 2019 were negative for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction, we found that coronavirus disease 2019 in term patients admitted to labor and delivery is associated with increased rates of placental histopathologic abnormalities, particularly fetal vascular malperfusion and villitis of unknown etiology. These findings seem to occur even among asymptomatic term patients.

Keywords: chronic intervillositis; fetal vascular malperfusion; malperfusion; maternal vascular; pregnancy; severe acute respiratory syndrome 2; villitis of unknown etiology.