Investigating Placental Pathologies in COVID-19 Positive Pregnancies Among the Pre-COVID and COVID Era

Abstract

Purpose: The overall objective of this study was to better understand the impact of COVID-19 infection during pregnancy, especially effects on placental pathologies; our central hypothesis is that COVID-19 positive placentas will demonstrate more placental vasculopathies than the pre-pandemic placentas and post-vaccine placentas. Methods: Under IRB-approved protocols (MU IRB #2022984, #2044102, #2057162), participants were recruited for this study, consented via phone, and consented for research studies using RedCAP. All research participants consented to having their placentas examined after delivery. Of note, multiple research participants were found to have prior deliveries at the University of Missouri Women and Children’s Hospital, and placentas from those previous deliveries were available for comparison purposes. Placentas were broken up into four groups, depending on if they belonged to women: (a) positive COVID-19 testing during pregnancy (b) never having a positive COVID-19 test during pregnancy, (c) pre-pandemic placenta for a woman with positive COVID-19 testing, or (d) pre-pandemic placenta for a woman who never had a positive COVID-19 test during pregnancy. These placentas were compared and contrasted for gross and microscopic pathologic findings associated with COVID-19 infection. Specifically, vasculopathies such as villous thrombi, perivillous fibrin deposition, and placental infarcts or necrosis. Signs of infection were also assessed, including acute chorioamnionitis or funicitis and acute chorionic plate vasculitis. More than twenty unique pathologic diagnoses were found among all placentas examined, and these findings were confirmed by a board-certified Anatomic Pathologist (EJ). Histologic examination consisted of hemoxylin and eosin staining after formalin fixation and paraffin-embedding of the histologic sections. Micropictography was utilized to obtain images of significant pathologic findings. Infection was confirmed using reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. Additionally, a thorough chart review was performed on the pregnancy course of each research participant associated with each placenta. Specifically, APGAR scores, liveborn status, newborn neonatal intensive care unit (NICU) stays, maternal vaccination status, and maternal comorbidities were identified. Results: 59 participants consented to having their placentas examined after delivery in 2020-2021. Of these 59 participants, 31 delivered at the University of Missouri Women and Children’s Hospital (WCH). Of these 31 participants, 12 women had their placentas sent for pathologic examination. Of these 12 women, 10 had a prior delivery at WCH pre-Covid, 1 had 2 previous deliveries at WCH pre-Covid, and one did not have a past delivery at WCH pre-Covid. 3 of these 12 women tested positive for COVID-19 infection while pregnant. Overall, 24 placentas were examined from 2020-2021, with the following major findings: 1.)Nine (9) placentas from research participants negative for COVID19, as compared to pre-pandemic placentas from the same mothers, had similar outcomes including the incidence of acute and chronic decidual inflammation. Interestingly, these pre-pandemic placentas had higher rates of chorioamnionitis and funicitis. 2.)Three (3) placentas from research participants with positive COVID-19 tests, compared to pre-pandemic placentas from the same mothers, had no major differences. Among this group, one patient had more severe pathologic vascular disease while COVID positive, compared to her earlier, pre-pandemic placenta in which that earlier pregnancy course involved pre-eclampsia. Additionally, positive COVID19 results earlier in pregnancy exhibited more severe pathologic findings than those testing positive during later stages of pregnancy. 3.)COVID-19 positive placentas delivered had more severe and diffuse infarcts than the COVID-19 negative placentas. Overall, in this limited case series, COVID-19 infection did not impact the clinical outcomes of either mother or newborn. No differences were seen in APGAR scores, live birth outcomes, percentile size (for gestational age), or days of NICU stay. Additionally, no women in this case series were found to be vaccinated for COVID-19 before the date of delivery. Conclusion: Microscopically, placentas from women with mild COVID-19 disease may be associated with a slightly higher risk of placental infarctions, and more severe placental findings with COVID-19 infections that occur earlier in pregnancy. The clinical significance of mild COVID-19 infections during pregnancy remains to be fully characterized and may warrant further investigation. Despite the end of the COVID-19 public health emergency, there also remain concerns about neurodevelopmental outcomes in the offspring of mothers who test positive for SARS-CoV-2 during pregnancy (Edlow, et al). More comparative studies with larger sample sizes, would help elucidate the potential effects of COVID19 infection on placental pathologies, as well as maternal and newborn outcomes.