Placental damage comparison between preeclampsia with COVID-19, COVID-19, and preeclampsia: analysis of caspase-3, caspase-1, and tumor necrosis factor-alpha expression

BACKGROUND: Some studies have reported that preeclampsia with COVID-19 significantly increases the risk of adverse perinatal outcomes to nearly 3-fold in normal pregnancy. In theory, the pathophysiology of preeclampsia increases perinatal mortality and morbidity starting from placental injury, which is also believed to share a common pathway with COVID-19. Moreover, major placental injuries could be apoptotic, necrotic, or pyroptotic. OBJECTIVE: This study aimed to compare the placental damage between Preeclampsia with COVID-19, COVID-19, and preeclampsia in apoptotic, necrotic, or pyroptotic injuries. STUDY DESIGN: This was an observational analytical study with a cross-sectional setting. A total of 72 pregnant women were admitted to the hospital with diagnoses of preeclampsia with COVID-19, preeclampsia, and COVID-19. The diagnosis for preeclampsia was following the International Federation of Gynecology and Obstetrics criteria with at least 1 of the severe features. Patients with COVID-19 were eligible if they had a confirmatory polymerase chain reaction test with moderate to severe clinical degree. The placentas were taken after delivery, and the parameters were quantified with immunohistochemistry tests for caspase-3, caspase-1, and tumor necrosis factor-alpha representing apoptotic, pyroptotic, and necrotic pathways, respectively. RESULTS: Pregnancies complicated by both COVID-19 and preeclampsia, preeclampsia, and COVID-19 significantly had the highest placental damage on apoptotic, pyroptotic, and necrotic pathways shown from caspase-3, caspase-1, and tumor necrosis factor-alpha expressions in the placenta (P<.05). Moderate to severe degree of COVID-19 resulted in higher placental damage than preeclampsia in all 3 forms (P<.05). The apoptotic process was the most prominent among the pathways. CONCLUSION: Preeclampsia with COVID-19 showed significant placental damage, with major changes related to apoptosis, inflammation, and necrosis. Our data support poor perinatal outcomes of pregnancies complicated by both preeclampsia and COVID-19.