Introduction
Newly diagnosed hypertension during pregnancy after 20 gestational weeks includes gestational hypertension and pre-eclampsia, affects about 6-8% of the pregnant population worldwide, and is a leading cause of maternal and perinatal morbidity and mortality.1 2 Current knowledge suggests that pregnancy does not increase susceptibility to the SARS-CoV-2 virus, but might worsen the manifestations of covid-19 compared with non-pregnant individuals of the same age.3
Severe covid-19 disease has been shown to have multiorgan effects and symptomatology, similar to those seen in individuals with hypertension during pregnancy. These effects include newly diagnosed hypertension, kidney injury, liver involvement, haematological complications, pathological placentas, and endothelial dysfunction, and therefore a biological link between infection by the SARS-CoV-2 virus and hypertension during pregnancy, specifically pre-eclampsia, has been suggested.4–6 A recent systematic review and meta-analysis showed that SARS-CoV-2 infection during pregnancy was associated with a significant increase in the odds of developing pre-eclampsia (pooled adjusted odds ratio 1.58, 95% confidence interval 1.39 to 1.80; P<0.001).6 The renin-angiotensin system is an important regulator of placental function because it modulates proliferation of trophoblasts, angiogenesis, and blood flow. It has been shown that the SARS-CoV-2 virus binds to the angiotensin converting enzyme 2 receptor expressing maternal and fetal cells in the placenta, leading to changes in the renin-angiotensin system, which might have a role in the suggested association between SARS-CoV-2 infection and pre-eclampsia.6
Severe covid-19 disease and pre-eclampsia share the same risk factors: pre-existing hypertension, obesity, advanced maternal age, diabetes,7 8 chronic kidney disease,9 and systemic lupus erythematosus.10 These factors could contribute to unmeasured confounding and thus cause spurious associations. Another potential bias is that pregnancies with early symptoms of hypertension are monitored more closely and have a higher probability of being tested for SARS-CoV-2 than pregnancies without adverse symptoms. This surveillance bias could introduce non-random misclassification of the risk factor and reversed causation. Only one11 of the included studies in the meta-analysis6 considered the time between infection and pre-eclampsia (ie, temporality).
Population based healthcare and quality registers from Sweden and Norway have detailed information on dates of positive test results for SARS-CoV-2 infection and confirmed diagnoses of hypertension during pregnancy. In this study, we looked at the association between SARS-CoV-2 infection and subsequent hypertension during pregnancy and pre-eclampsia, taking into account temporality and confounding.