Pregnancy Outcomes During the Pandemic: Using Placental Pathology and Gene Expression to Understand Fetal Risk

The current outbreak of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares similarities to the severe acute respiratory syndrome (SARS) disease outbreak (2002 - 2003) and the ongoing Middle East respiratory syndrome (MERS) outbreak which originated in 2012. All three infections present with a cough, fever, and the potential for lower respiratory tract disease. While SARS and MERS maintain a higher case fatality rate (CFR), the higher transmissibility for COVID-19 results in larger number of cases and deaths. Severe respiratory infections which commonly result in pneumonia, such as SARS and influenza A H1N1, are associated with an increased risk for maternal mortality and stillbirth. Although current evidence does not suggest a higher maternal risk of infection than the general population, little is known on the impact of the infection on pregnancy and adverse neonatal outcomes. A systematic review of Coronavirus spectrum infections reported an 11% increase rate of perinatal death. The exact mechanisms of perinatal deaths are not well characterized.

While there is little evidence to date that suggests SARS-CoV-2 infection is vertically transmissible to the fetus, angiotensin-converting enzyme 2 (ACE2), the confirmed receptor for SARS-CoV-2, has been detected at high levels in the early human placenta and presents with tissue specific activity patterns. Villous cytotrophoblast and syncytiotrophoblast cells exhibit high levels of ACE2 expression during the first trimester while expression in the extravillous trophoblast layer starts low during early pregnancy and then peaks around 24 weeks gestation. Disruption in the vascularization and/or metabolic capacity of the placenta could result in placental insufficiency and suboptimal fetoplacental growth and development. A prior study on placental findings from patients with COVID-19 demonstrated an increase in decidual arteriopathy and patterns of maternal vascular malperfusion (MVM), many of whom were asymptomatic from COVID-19. Additionally, a portion of patients with COVID-19 during pregnancy will experience pneumonia and subsequent hypoxia. We hypothesize that exposure to hypoxemia and maternal respiratory failure may further threaten metabolic demands of the fetoplacental unit during gestation.

Our primary research hypothesis is that COVID-19 disease impacts placental development and function and is mediated by severity and duration of illness. We hypothesize that the impact on placental development will subsequently increase adverse fetal outcomes.

This is a case control research project that will utilize patient data (including chart history) and placental specimens collected from Greenville Memorial Hospital between June 2020 and June 2021 during the COVID-19 outbreak. Controls will be matched using banked placental and cord blood specimens collected at Greenville Memorial Hospital or Northshore University Health system prior to emergence of the COVID-19 outbreak, between March 2017 and December 2019. We plan to use banked samples given the potentially high rate of asymptomatic cases. At the conclusion of the study, samples and data collected at Greenville Memorial Hospital will be deidentified and combined with samples collected at NorthShore University Health Center for subsequent analysis and publication.

Potentially eligible patients will be identified during their routine prenatal care at the Prisma Health OB/GYN Center, through the Prisma Health COVID-19 Registry, or when they are admitted to Greenville Memorial Hospital for delivery. Patients will be evaluated for eligibility based on a review of the medical record. Patients identified prior to hospital admission may be consented at their next prenatal care visit at the OB/GYN Center, Maternal-Fetal Medicine Unit, or when they arrive at Greenville Memorial for delivery. Patients identified as eligible prior to hospital admission for delivery will be marked as eligible under the research tab in their chart. Patients identified prior to hospital admission may be consented and enrolled at their next prenatal care visit at the OB/GYN Center, Maternal-Fetal Medicine Unit, or when they arrive at Greenville Memorial for delivery.