Antepartum SARS-CoV-2 infection and adverse birth outcomes in South African women

Background SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking. Methods We conducted a longitudinal study from April 2020 to March 2021, in South Africa, where symptomatic or asymptomatic pregnant women were investigated for SARS-CoV-2 infection during the antepartum period. We aimed to evaluate if there was an association between antepartum SARS-CoV-2 infection on birth outcomes. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT), histological examination was performed in a sub-set of placentas. Results Overall, 793 women were tested for SARS-CoV-2 antenatally, including 275 (35%) who were symptomatic. SARS-CoV-2 infection was identified in 138 (17%) women, of whom 119 had symptoms (COVID-19 group) and 19 were asymptomatic. The 493 women who were asymptomatic and had a negative SARS-CoV-2 NAAT were used as the referent comparator group for outcomes evaluation. Women with COVID-19 compared with the referent group were 1.66-times (95% confidence interval (CI) = 1.02-2.71) more likely to have a low-birthweight newborn (30% vs 21%) and 3.25-times more likely to deliver a very low-birthweight newborn (5% vs 2%). Similar results for low-birthweight were obtained comparing women with SARS-CoV-2 confirmed infection (30%) with those who had a negative NAAT result (22%) independent of symptoms presentation. The placentas from women with antenatal SARS-CoV-2 infection had higher percentage of chorangiosis (odds ratio (OR) = 3.40, 95% CI = 1.18-.84), while maternal vascular malperfusion was more frequently identified in women who tested negative for SARS-CoV-2 (aOR = 0.28, 95% CI = 0.09-0.89). Conclusions Our study demonstrates that in a setting with high HIV infection prevalence and other comorbidities antenatal SARS-CoV-2 infection was associated with low-birthweight delivery.

and demonstrates nuclear dust with extravasation of red cells into the villous stroma with preservation of the surrounding trophoblast. FVM may be global (partial umbilical cord obstruction) or segmental (complete) and either may be high grade or low grade.
Abruption is a clinical diagnosis, but the corresponding pathological term is retroplacental haemorrhage.
Macroscopic retroplacental haemorrhage was defined as an indentation (with or without adherent clot) of >15% of the maternal surface of the placenta, possibly with bleeding seen tracking into the placental parenchyma after the placenta is sliced and the slices are laid out flat on the surface of the cutting table.
The microscopic criteria for retroplacental haemorrhage were the presence of blood beneath the decidua, dissecting into the decidua and placental parenchyma, with congestion, and/or intravillous haemorrhage (haemorrhage into villous stroma). There may be additional coagulation necrosis of the syncytiotrophoblast nuclei with overlying infarction.

Features of infection included chorioamnionitis (ascending infection), and villitis which was divided into
infectious and non-infectious chronic villitis or villitis of unknown aetiology.
Ascending infection or chorioamnionitis was defined as neutrophils in the placenta -maternal responsewith or without the involvement of the umbilical cord vessels (vein and arteries or funisitis). The location of the inflammation within the membranes of the chorionic plate, and additional features such as subchorionic micro-abscesses were recorded.
Villitis was recorded as acute (extremely uncommon) or chronic.If features such as plasma cells, granulomas, multinucleated giant cells, normoblasts in foetal vessels and hemosiderin within sclerotic villi or an accompanying necrotising funisitis were present, further investigations were undertaken to exclude a specific infective aetiology such as cytomegalovirus, Treponema pallidum or toxoplasmosis (3).
The remainder were designated as chronic non-specific villitis or villitis of unknown aetiology, a maternal T-lymphohistiocytic response to foetal antigens. These were graded as high grade or low grade and the presence of obliterative foetal vasculopathy noted, as it has prognostic significance (4). The cell type was noted as lymphocytic, histiocytic or a combination of both.
The association of chronic lymphohistiocytic villitis with chronic histiocytic villitis and perivillous fibrin was specifically noted in view of the current literature described in patients with COVID-19.
3 Chronic Histiocytic Intervillositis is an infiltrate of the intervillous space or maternal blood by CD68+ histiocytes, with or without accompanying fibrin, and rarely with a minor component of chronic villitis.
Amnion nodosum is deposition of foetal squames and vernix on the membranes, usually associated with severe oligohydramnios. It may be a marker for pulmonary hypoplasia and renal abnormalities in the foetus.
Further pathological lesions indicative of non-specific placental injury/foetal compromise recorded were villous edema (focal or diffuse), increased foetal nucleated red blood cells, and chorangiosis (focal and diffuse). Odds Ratio (aOR) adjusted for HIV status (infected, uninfected), comorbid conditions (yes, no), pregnancy related complications (yes, no), previous premature births (yes, no), and time between diagnosis and delivery (categorical variable); for aOR, records numbers are less due to missing data in variables used for adjustment. Odds Ratio in bold are statistically significant. Odds Ratio (aOR) adjusted for HIV status (negative, positive), comorbid conditions (yes, no) and pregnancy related complications (yes, no); for aOR, records numbers are less due to missing data in variables used for adjustment. Odds Ratio in bold are statistically significant.