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Comparison of Severe Maternal Morbidities Associated With Delivery During Periods of Circulation of Specific SARS-CoV-2 Variants

Educational Objective
To identify the key insights or developments described in this article
Key Points

Question  Does the association between SARS-CoV-2 infection and severe maternal morbidity (SMM), including nonrespiratory complications, vary by viral strain?

Findings  In this retrospective cohort study of 3129 patients with SARS-CoV-2 infection and 12 504 patients without infection giving birth in a large US health system between March 2020 and January 2022, the risk of SMM associated with SARS-CoV-2 infection was significantly higher during the phase of the pandemic when the Delta variant was predominant (July 2021-November 2021). This association was also noted specifically for both respiratory and nonrespiratory SMM.

Meaning  These findings highlight the importance of the prevention of SARS-CoV-2 infection in pregnant individuals and the consideration of infection as a risk factor for adverse peripartum maternal outcomes.


Importance  Infection with SARS-CoV-2, which causes COVID-19, is associated with adverse maternal outcomes. While it is known that severity of COVID-19 varies by viral strain, the extent to which this variation is reflected in adverse maternal outcomes, including nonpulmonary maternal outcomes, is not well characterized.

Objective  To evaluate the associations of SARS-CoV-2 infection with severe maternal morbidities (SMM) in pregnant patients delivering during 4 pandemic periods characterized by predominant viral strains.

Design, Setting, and Participants  This retrospective cohort study included patients delivering in a multicenter, geographically diverse US health system between March 2020 and January 2022. Individuals with SARS-CoV-2 infection were propensity-matched with as many as 4 individuals without evidence of infection based on demographic and clinical variables during 4 time periods based on the dominant strain of SARS-CoV-2: March to December 2020 (wild type); January to June 2021 (Alpha [B.1.1.7]); July to November 2021 (Delta [B.1.617.2]); and December 2021 to January 2022 (Omicron [B.1.1.529]). Data were analyzed from October 2021 to June 2022.

Exposures  Positive SARS-CoV-2 nucleic acid amplification test result during the delivery encounter.

Main Outcomes and Measures  The primary outcome was any SMM event, as defined by the US Centers for Disease Control and Prevention, during hospitalization for delivery. Secondary outcomes were number of SMM, respiratory SMM, nonrespiratory SMM, and nontransfusion SMM events.

Results  Over all time periods, there were 3129 patients with SARS-CoV-2, with a median (IQR) age of 29.1 (24.6-33.2) years. They were propensity matched with a total of 12 504 patients without SARS-CoV-2, with a median (IQR) age of 29.2 (24.7-33.2) years. Patients with SARS-CoV-2 infection had significantly higher rates of SMM events than those without in all time periods, except during Omicron. While the risk of any SMM associated with SARS-CoV-2 infection was increased for the wild-type strain (odds ratio [OR], 2.74 [95% CI, 1.85-4.03]) and Alpha variant (OR, 2.57 [95% CI, 1.69-4.01]), the risk during the Delta period was higher (OR, 7.69 [95% CI, 5.19-11.54]; P for trend < .001). The findings were similar for respiratory complications, nonrespiratory complications, and nontransfusion outcomes. For example, the risk of nonrespiratory SMM events for patients with vs without SARS-CoV-2 infection were similar for the wild-type strain (OR, 2.16 [95% CI, 1.40-3.27]) and Alpha variant (OR, 1.96 [95% CI, 1.20-3.12]), highest for the Delta variant (OR, 4.65 [95% CI, 2.97-7.29]), and not significantly higher in the Omicron period (OR, 1.21 [95% CI, 0.67-2.08]; P for trend < .001).

Conclusions and Relevance  This cohort study found that the SARS-CoV-2 Delta variant was associated with higher rates of SMM events compared with other strains. Given the potential of new strains, these findings underscore the importance of preventive measures.

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Article Information

Accepted for Publication: June 3, 2022.

Published: August 12, 2022. doi:10.1001/jamanetworkopen.2022.26436

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Mupanomunda M et al. JAMA Network Open.

Corresponding Author: Frederick A. Masoudi, MD, MSPH, Ascension Health, 3600 Edmundson Rd, St Louis MO 63134 (frederick.masoudi@ascension.org).

Author Contributions: Mr Miller and Dr Ottenbacher had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Mupanomunda, Fakih, Miller, Gianopoulos, Cacchione, Fogel, Aloia, Masoudi.

Acquisition, analysis, or interpretation of data: Mupanomunda, Fakih, Miller, Ottenbacher, Winegar, Roberts, Kimathi, Gianopoulos, Cahill, Aloia, Masoudi.

Drafting of the manuscript: Mupanomunda, Fakih, Miller, Kimathi, Masoudi.

Critical revision of the manuscript for important intellectual content: Mupanomunda, Fakih, Miller, Ottenbacher, Winegar, Roberts, Gianopoulos, Cahill, Cacchione, Fogel, Aloia.

Statistical analysis: Miller, Winegar, Roberts, Gianopoulos.

Administrative, technical, or material support: Mupanomunda, Ottenbacher, Winegar, Roberts, Kimathi, Gianopoulos, Cacchione, Aloia.

Supervision: Mupanomunda, Fakih, Winegar, Gianopoulos, Fogel, Aloia, Masoudi.

Conflict of Interest Disclosures: None reported.

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