COVID-19 and Hypertensive Disorders of Pregnancy (HDP): A Portuguese Multicentric Retrospective Cohort Study of HDP in SARS-CoV-2 Infected Patients

Background: An increased incidence of hypertensive disorders of pregnancy (HDP) has been reported among pregnant women infected by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen behind coronavirus disease-19 (COVID-19). Although it is primarily a respiratory infection, the extra-pulmonary manifestations of COVID-19 mimic those found in preeclampsia (PE). Moreover, the two conditions share common risk factors and pathological mechanisms, hindering the ability to understand the interaction between them. Current literature on this topic is controversial and as there is an overlap of clinical and laboratory findings, HDP can be an overreported outcome in pregnant women with COVID-19. The aim of our study is to assess whether there is an association between maternal SARS-CoV-2 infection and HDP. Methods: We designed a multicenter retrospective cohort study with data collected from five maternity hospitals in Almada, Porto, Lisboa, Penafiel and Coimbra, Portugal, between March 2020 and March 2021. We obtained a sample of 789 pregnant women who were followed up or delivered their babies in one of the participating centers. Each pregnant woman who tested positive for SARS-CoV-2 on a real-time polymerase chain reaction test -- exposure group (n= 263), was paired with two negative pregnant women (1:2), who received the same antenatal care and had similar gestational age and parity -- control group (n=526). Data were collected on maternal characteristics, medical history, obstetric outcomes, and delivery. Outcomes: The primary outcome of our study is to assess the incidence of HDP in pregnant women infected and not infected by SARS-CoV-2. The secondary outcomes of our study are to assess the incidence of HDP across all COVID-19 severity subgroups and to assess whether SARS-CoV-2 infection in pregnancy modified the odds of a set of risk factors developing HDP. Results: There was a slightly increased, but not statistically significant, incidence of PE (relative risk, RR, 1.33; 95% confidence interval, CI 0.68-2.57) in the SARS-CoV-2 positive group. There was no statistically significant association between having COVID-19 in pregnancy and developing PE/eclampsia/ hemolysis, elevated liver enzymes, and low platelets, HELLP syndrome [X2(1) = 0.732; p = 0.392] as well as developing gestational hypertension (GH) [X2(1) = 0.039; p = 1]. There was no statistically significant association [X(2)(2) = 0.402; p = 0.875), [X(2)(2) = 1.529; p = 0.435] between COVID-19 severity and incidence of HDP. The SARS-CoV-2 infection did not modify the odds of each maternal risk factor causing HDP. Conclusion: Our study did not demonstrate an association between maternal COVID-19 and HDP. We did not observe a significantly increased incidence of HDP in pregnant women infected by SARS-CoV-2. As current literature is controversial on this topic, clinicians should be aware that HDP is a possible complication of maternal SARS-CoV-2 infection and further research studies urge to better assess the association between COVID-19 in pregnancy and HDP.