AJOG: SARS-COV-2 infection during pregnancy and risk of preeclampsia: a systematic review and meta-analysis



To examine the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and the risk of preeclampsia.


MEDLINE, EMBASE, POPLINE, CINAHL, LILACS, and WHO COVID-19, Chinese, and preprint databases (all from December 1, 2019 to May 31, 2021). Google Scholar, bibliographies, and conference proceedings were also searched.


Observational studies that assessed the association between SARS-CoV-2 infection during pregnancy and preeclampsia and that reported unadjusted and/or adjusted risk estimates and 95% confidence intervals (CIs) or data to calculate them.


The primary outcome was preeclampsia. Secondary outcomes included preeclampsia with severe features, preeclampsia without severe features, eclampsia, and the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Two reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled unadjusted and adjusted odds ratios (ORs) with 95% CIs, and 95% prediction interval were calculated. Heterogeneity was quantified with the І2 statistic, where І2 ≥30% indicated substantial heterogeneity. Subgroup and sensitivity analyses were performed for testing the robustness of the overall findings.


Twenty-eight studies that included 790,954 pregnant women, among which 15,524 were diagnosed with SARS-CoV-2 infection, met the inclusion criteria. The meta-analysis of unadjusted ORs showed that the odds of developing preeclampsia were significantly higher among pregnant women with SARS-CoV-2 infection than among those without SARS-CoV-2 infection (7.0% vs 4.8%; pooled OR 1.62, 95% CI 1.45-1.82; P <0.00001; І2=17%; 26 studies; 95% prediction interval of the OR, 1.28-2.05). The meta-analysis of adjusted ORs also showed that SARS-CoV-2 infection during pregnancy was associated with a significant increase in the odds of preeclampsia (pooled OR 1.58, 95% CI 1.39-1.80; P <0.0001; І2=0%; 11 studies). There was a statistically significant increase in the odds of preeclampsia with severe features (OR 1.76, 95% CI 1.18-2.63; І2=58%; 7 studies), eclampsia (OR 1.97, 95% CI 1.01-3.84; І2=0%, 3 studies), and HELLP syndrome (OR 2.10, 95% CI 1.48-2.97; 1 study) among pregnant women with SARS-CoV-2 infection, as compared to those without the infection. Overall, the direction and magnitude of the effect of SARS-CoV-2 infection during pregnancy on preeclampsia was consistent across most pre-specified subgroup and sensitivity analyses. Both asymptomatic and symptomatic SARS-CoV-2 infections significantly increased the odds of preeclampsia although it was higher among patients with symptomatic illness (OR 2.11, 95% CI 1.59-2.81) than among those with asymptomatic illness (OR 1.59, 95% CI 1.21-2.10).


SARS-CoV-2 during pregnancy is associated with higher odds of preeclampsia.