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

https://doi.org/10.1016/j.ajog.2021.07.009Get rights and content

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.

Key words

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

Cited by (0)

The authors report no conflict of interest.

This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, by federal funds from the NICHD/NIH/DHHS under contract number HHSN275201300006C.

R.R. has contributed to this work as part of his official duties as an employee of the United States Federal Government.

The funder had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.

Reprints will not be available.

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