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

Abstract

Objective: To examine the relationship between SARS-CoV-2 infection during pregnancy and the risk for preeclampsia.

Data sources: MEDLINE, Embase, POPLINE, CINAHL, LILACS, and the World Health Organization COVID-19, Chinese, and preprint databases (all from December 1, 2019, to May 31, 2021). Google Scholar, bibliographies, and conference proceedings were also searched.

Study eligibility criteria: 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 or data to calculate them.

Study appraisal and synthesis methods: The primary outcome was preeclampsia. Secondary outcomes included preeclampsia with severe features, preeclampsia without severe features, eclampsia, and 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 with 95% confidence intervals, and 95% prediction interval were calculated. Heterogeneity was quantified using the І² statistic, for which І²≥30% indicated substantial heterogeneity. Subgroup and sensitivity analyses were performed to test the robustness of the overall findings.

Results: A total of 28 studies comprising 790,954 pregnant women, among which 15,524 were diagnosed with SARS-CoV-2 infection, met the inclusion criteria. The meta-analysis of unadjusted odds ratios 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 odds ratio, 1.62; 95% confidence interval, 1.45-1.82; P<.00001; І²=17%; 26 studies; 95% prediction interval of the odds ratio, 1.28-2.05). The meta-analysis of adjusted odds ratios also showed that SARS-CoV-2 infection during pregnancy was associated with a significant increase in the odds of preeclampsia (pooled odds ratio, 1.58; 95% confidence interval, 1.39-1.80; P<.0001; І²=0%; 11 studies). There was a statistically significant increase in the odds of preeclampsia with severe features (odds ratio, 1.76; 95% confidence interval, 1.18-2.63; І²=58%; 7 studies), eclampsia (odds ratio, 1.97; 95% confidence interval, 1.01-3.84; І²=0%, 3 studies), and HELLP syndrome (odds ratio, 2.10; 95% confidence interval, 1.48-2.97; 1 study) among pregnant women with SARS-CoV-2 infection when 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 prespecified subgroup and sensitivity analyses. Both asymptomatic and symptomatic SARS-CoV-2 infections significantly increased the odds of developing preeclampsial; however, it was higher among patients with symptomatic illness (odds ratio, 2.11; 95% confidence interval, 1.59-2.81) than among those with asymptomatic illness (odds ratio, 1.59; 95% confidence interval, 1.21-2.10).

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

Keywords: COVID-19; HELLP syndrome; coronavirus; eclampsia; hepatic damage; hypertension; hypertensive disorders of pregnancy; liver enzymes; maternal morbidity; preeclampsia with severe features; preeclampsia without severe features; proteinuria; thrombocytopenia; viral infection.

Figure 1

Flow diagram of the study selection process Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Figure 2

Meta-analysis of unadjusted odds ratios for the association between SARS-CoV-2 infection during pregnancy and preeclampsia Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Figure 3

Meta-analysis of adjusted odds ratios for the association between SARS-CoV-2 infection during pregnancy and preeclampsia Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Supplemental Figure 1

Risk of bias for each included study Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Supplemental Figure 2

Funnel plot of the meta-analysis on the association between SARS-CoV-2 infection during pregnancy and preeclampsia Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Supplemental Figure 3

Funnel plot of the meta-analysis on the association between SARS-CoV-2 infection during pregnancy and preeclampsia after applying the “Trim and Fill” method∗ Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.

Supplemental Figure 4

Meta-analysis of unadjusted odds ratios for the risk of preeclampsia during the COVID-19 pandemic in comparison to before the pandemic CI, confidence interval. Conde-Agudelo. Association between SARS-CoV-2 infection during pregnancy and preeclampsia. Am J Obstet Gynecol 2022.