Faculty Bibliography

BACKGROUND:- There is a paucity of data describing the effects of COVID-19, especially in asymptomatic patients, on placental pathology. Although the pathophysiology of COVID-19 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:- The aim of this study was to determine whether COVID-19 in term patients admitted to Labor and Delivery, including women without COVID-19 symptomatology, is associated with increased placental injury compared to a cohort of COVID-19 negative controls. STUDY DESIGN/METHODS:- This was a retrospective cohort study performed at NYU Winthrop Hospital between 3/31/2020 and 6/17/2020. During the study period all women admitted to Labor and Delivery were routinely tested for SARS-CoV-2 regardless of symptomatology. The placental histopathological findings of COVID-19 patients (n=77) who delivered a singleton gestation at term were compared to a control group of term patients without COVID-19 (n=56). Controls were excluded if they had obstetric or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy or thrombophilia. Multivariable logistic regression models were performed for variables that were significant in univariable analyses. A subgroup analysis was also performed comparing asymptomatic COVID-19 cases to negative controls. RESULTS:- In univariable analyses, COVID-19 cases were more likely to have evidence of fetal vascular malperfusion, i.e. presence of avascular villi and/or mural fibrin deposition (32.5% (25/77) vs. 3.6% (2/56), p<0.0001) and villitis of unknown etiology (20.8% (16/77) vs. 7.1% (4/56), p=0.030). These findings persisted in a subgroup analysis of asymptomatic COVID-19 cases compared to COVID-19 negative controls. In a multivariable model adjusting for maternal age, race/ethnicity, mode of delivery, preeclampsia, fetal growth restriction and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the COVID-19 group (OR= 12.63, 95% CI [2.40, 66.40]). While the frequency of villitis of unknown etiology was more than double in COVID-19 cases compared to controls, this did not reach statistical significance in a similar multivariable model (OR=2.11, 95% CI [0.50, 8.97]). All neonates of mothers with COVID-19 tested negative for SARS-CoV-2 by PCR. CONCLUSIONS:- Despite the fact that all neonates born to mothers with COVID-19 were negative for SARS-CoV-2 by PCR, we found that COVID-19 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 appear to occur even among asymptomatic term patients.

BACKGROUND:While elevated second trimester maternal serum alpha fetoprotein (msAFP) has been associated with adverse pregnancy outcomes, the utility of first trimester msAFP in predicting these outcomes is limited. Some laboratories have been including msAFP as part of the first trimester analyte screening for aneuploidy and preeclampsia, offering its potential utility in predicting pregnancy outcomes. OBJECTIVE:Our primary objective was to determine the association between elevated first trimester msAFP and preeclampsia, as well as ischemic placental disease (a composite of preeclampsia, fetal growth restriction and/or placental abruption). Secondary outcomes included early onset preeclampsia requiring delivery at <34 weeks gestation, fetal growth restriction, placental abruption, preterm delivery, fetal demise, and spontaneous abortion. STUDY DESIGN/METHODS:An IRB-approved multi-site retrospective cohort study was performed including all patients with first trimester msAFP as part of routine first trimester aneuploidy screening from April 2015-January 2017. Pregnancies with multiple gestations, known structural or chromosomal abnormalities, known malignancy, and incomplete delivery records were excluded. Delivery records were reviewed for baseline characteristics and adverse pregnancy outcomes. The optimal cut-off point for first trimester msAFP to predict these outcomes was assessed and an elevated msAFP was considered > 2.0 MoM. Fisher exact test and odds ratios were used to determine the association between elevated first trimester msAFP and adverse pregnancy outcomes. Spearman correlation coefficient assessed the relationship between first and second trimester msAFP. RESULTS:Of 1478 patients with first trimester msAFP, 1280 had complete records available for review (86.6%). There was no association demonstrated between elevated first trimester msAFP (> 2.0 MoM) and the primary outcome, overall preeclampsia (5.8% vs. 4.6%, OR 1.29, 95% CI 0.58, 2.91). However, there was an increased incidence of ischemic placental disease, 15.8% vs 7.7% (OR 2.26, 95% CI 1.33-3.87) in those with an elevated AFP. Also, elevated first trimester msAFP was associated with a higher incidence of fetal growth restriction (7.5% vs 2.3%, OR 3.40, 95% CI 1.56-7.42) and preterm birth (18.3% vs 10.3%, OR 1.95, 95% CI 1.18-3.21). Also, a positive correlation between first and second trimester msAFP was demonstrated (rho = 0.46, P< 0.0001). CONCLUSIONS:Elevated first trimester msAFP is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated msAFP may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine if addition of first trimester msAFP to existing algorithms can improve the early detection of ischemic placental disease.