The effects of preconception and early gestation SARS-CoV-2 infection on pregnancy outcomes and placental pathology

Abstract

Objective: To evaluate if peri-pregnancy timing of a PCR+ test for SARS-CoV-2 RNA affects pregnancy outcomes and placental pathology.

Methods: This is a retrospective cohort study conducted in a tertiary center. Pregnancy outcomes and placental pathology were compiled for women who tested positive for SARS-CoV-2 RNA from a nasopharyngeal swab assessed by RT-PCR. The population comprised four groups that were PCR+ preconception (T₀) or in the 1st (T₁), 2nd (T₂), or 3rd (T₃) trimester of pregnancy. A fifth, control group (T_C) tested PCR- for SARS-CoV-2 before delivery.

Results: Seventy-one pregnancies were studied. The T₀ group exhibited lower gestational ages at delivery, had infants with the lowest birth weights, the highest rate of pregnancy loss before 20 weeks. Features of maternal vascular malperfusion and accelerated villous maturation were prominent findings in the histopathology of placentas from women PCR+ for SARS-CoV-2 RNA, especially in the T₀ and the T₁ groups.

Conclusion: Women at highest risk for pregnancy complications are those who test PCR+ for viral RNA preconception or during first trimester of pregnancy.

Keywords: COVID-19; Neonatal outcome; Placental pathology; Pregnancy outcome; SARS-CoV-2; Timing.

Fig. 1

A: Distribution and comparison of gestational ages at delivery among groups – T₀, T₁, T₂, T₃, and T_C (P = 0.01). Significance difference seen due to comparison of T₀ with remaining groups. B: Differences in birth weight among groups, P < 0.01 (T₀ = COVID-19 before pregnancy; T₁ = COVID-19 during 1st of gestation; T₂ = 2nd of gestation; T₃ = 3rd of gestation; T_C = no COVID). Significance difference seen due to comparison of T₀ with remaining groups.

Fig. 2

Typical histopathology of placentas from patients who tested PCR+ for SARS-CoV-2 RNA. A: Villous morphology of a placenta at 32 weeks GA, appearing unusually similar to villi of a term placenta, with numerous small diameter or hyper mature villi. H&E, 40×. B: Avascular villi from a placenta delivered at 39 weeks' GA from a patient PCR+ for SARS-CoV-2 RNA. There are normal villi with fetal villous blood vessels apparent in the upper field, but the central portion shows chorionic villi with loss of fetal villous capillaries and deposits of hyaline fibrosis. H&E, 200×. C: Acute chorioamnionitis with numerous neutrophils distributed from the sub chorionic intervillous space (bottom) to the amniocyte covering the chorionic plate (top). H&E, 100×. D: High grade villitis of unknown etiology, with inflammatory cells colonizing more than ten adjacent villi. H&E, 200×. E: SARS-CoV-2 placentitis showing the triad of histiocytic inter-villositis, intervillous fibrin deposition and trophoblastic necrosis. H&E, 100×. F: Image of SARS-CoV-2 placentitis after specimen immunostaining for CD68 as a histiocyte, macrophage marker. The field shows the triad listed in E, with intervillous space cells immune-stained for CD68. 100×.