Date of Award

2023

Document Type

Dissertation

Degree Name

Master of Medicine (MMed)

First Supervisor/Advisor

Dr Ingrid Gichere

Second Supervisor/Advisor

Dr Patricia Okiro

Third Supervisor/Advisor

Prof. Marleen Temmerman

Department

AKU-East Africa

Abstract

Introduction: Coronavirus disease (COVID-19) is a significant cause of morbidity and mortality among pregnant women. Pregnant women infected with SARS-CoV-2 are at a greater risk of pre-eclampsia/eclampsia, non-iatrogenic preterm birth, stillbirth, and small for gestational age infants/fetal growth restriction (SGA/FGR), which share a common placental etiology. Placental histopathological changes attributed to COVID-19 have been demonstrated but there is a knowledge gap in how these changes impact pregnancy outcomes particularly those of placental origin.

Objectives: To investigate if there is an association between placental histopathology (maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute and chronic inflammatory pathology, and other findings according to the Amsterdam Placental Workshop Consensus Statement) in pregnant women with confirmed COVID-19 and adverse obstetric outcomes (non-iatrogenic preterm birth, pre-eclampsia, stillbirth and small for date/fetal growth restriction.

Methods: The study was nested in the global WHO-supported multicounty prospective study ‘A prospective cohort study investigating maternal, pregnancy and neonatal outcomes for women and neonates infected with SARS-CoV-2’. The histopathological analysis included gross examination and light microscopy on hematoxylin and eosin (H&E) according to the Amsterdam Placental Consensus Statement. Frequencies, proportions, risk ratios, and their 95% confidence intervals were calculated to compare pregnancy outcomes and placental histopathology.

Results: A total of 193 patients agreed to participate in the study and their placenta was collected. One hundred and twenty-four placentas were excluded as lacking a definitive RT-PCR/antigen SARS COV-2 test in pregnancy. Sixty-nine placentas were included for analysis. The composite pregnancy outcome occurred in 14 pregnancies. Maternal vascular malperfusion was detected in 20% and FVM in 16% of placentas with COVID-19. Thirteen percent of placentas showed acute inflammatory pathology and 23% of chronic inflammatory pathology. Increased perivillous deposition, trophoblastic necrosis, or chronic histiocytic intervillositis were detected in 7.2% of placentas. Placental histopathology did not vary by the composite pregnancy outcome, vaccination status, or the severity of COVID-19. Fetal vascular malperfusion was significantly higher in patients with the composite adverse outcome OR 4.69 (95%CI 1.04-22.10 p 0.04) while there was no association between other placental pathology and the composite adverse outcome.

Conclusion: In placentas women with confirmed SARS-CoV-2 during pregnancy, a significant proportion showed histopathological abnormalities suggesting placental malperfusion and inflammation. There is an increased risk of FVM in patients with the composite adverse pregnancy outcome which should be confirmed in future large prospective, blinded studies.

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