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Infectious Diseases

Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications

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

1 Credit CME

JAMA

Published Online: February 7, 2022

Original Investigation

Article Information and Disclosures

Torri D. Metz, MD, MS¹;

Rebecca G. Clifton, PhD²;

Brenna L. Hughes, MD, MS³;

Grecio J. Sandoval, PhD²;

William A. Grobman, MD, MBA⁴;

George R. Saade, MD⁵;

Tracy A. Manuck, MD, MS³;

Monica Longo, MD, PhD⁶;

Amber Sowles, BSN, RN¹;

Kelly Clark, BSN, RN³;

Hyagriv N. Simhan, MD⁷;

Dwight J. Rouse, MD⁸;

Hector Mendez-Figueroa, MD⁹;

Cynthia Gyamfi-Bannerman, MD, MS¹⁰;

Jennifer L. Bailit, MD, MPH¹¹;

Maged M. Costantine, MD¹²;

Harish M. Sehdev, MD¹³;

Alan T. N. Tita, MD, PhD¹⁴;

George A. Macones, MD¹⁵;

for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network

Author Affiliations

¹Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City
²George Washington University Biostatistics Center, Washington, DC
³Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill
⁴Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois
⁵Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston
⁶Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
⁷Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania
⁸Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island
⁹Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston, Children’s Memorial Hermann, Hospital, Houston
¹⁰Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University, New York, New York
¹¹MetroHealth Medical Center, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Case Western Reserve University, Cleveland, Ohio
¹²Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Ohio State University, Columbus
¹³Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia
¹⁴Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham
¹⁵Department of Women’s Health, University of Texas at Austin

National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Networkfor the

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Key Points

Question Among pregnant and postpartum individuals, is SARS-CoV-2 infection associated with increased risk of maternal mortality or serious morbidity from obstetric complications?

Findings In this retrospective cohort study that included 14 104 patients, a composite outcome of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2 occurred significantly more frequently in individuals with SARS-CoV-2 infection compared with individuals without SARS-CoV-2 infection (13.4% vs 9.2%, respectively).

Meaning Among pregnant and postpartum individuals, SARS-CoV-2 infection was associated with increased risk of a composite outcome of maternal mortality or serious morbidity from obstetric complications.

Abstract

Importance It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity.

Objective To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications.

Design, Setting, and Participants Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period.

Exposures SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity.

Main Outcomes and Measures The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth.

Results Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, −1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, −1.4% [95% CI, −3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]).

Conclusions and Relevance Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.

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Article Information

Corresponding Author: Torri D. Metz, MD, MS, University of Utah Health, 30 N 1900 E, SOM 2B200, Salt Lake City, UT 84132 (torri.metz@hsc.utah.edu).

Accepted for Publication: January 21, 2022.

Published Online: February 7, 2022. doi:10.1001/jama.2022.1190

Author Contributions: Drs Metz and Clifton 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: Metz, Clifton, Hughes, Grobman, Manuck, Longo, Sowles, Clark, Mendez-Figueroa, Gyamfi-Bannerman, Costantine, Tita, Macones.

Acquisition, analysis, or interpretation of data: Metz, Clifton, Hughes, Sandoval, Grobman, Saade, Manuck, Sowles, Clark, Simhan, Rouse, Mendez-Figueroa, Gyamfi-Bannerman, Bailit, Costantine, Sehdev, Tita, Macones.

Drafting of the manuscript: Metz, Clifton, Sandoval.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Clifton, Sandoval.

Obtained funding: Metz, Clifton, Grobman, Saade, Clark, Simhan, Rouse, Tita.

Administrative, technical, or material support: Metz, Clifton, Manuck, Longo, Sowles, Clark, Simhan, Rouse, Mendez-Figueroa, Bailit, Costantine, Tita, Macones.

Supervision: Metz, Clifton, Manuck, Clark, Rouse, Bailit, Sehdev, Tita, Macones.

Conflict of Interest Disclosures: Dr Metz reported receiving personal fees from Pfizer for her role as a medical consultant for a study of SARS-CoV-2 vaccination in pregnancy and grants from Pfizer for her roles as a site principal investigator [PI] for a study of SARS-CoV-2 vaccination in pregnancy and as a site PI for a study of respiratory syncytial virus vaccination in pregnancy, and from Gestvision for her role as a site PI for a preeclampsia study outside the submitted work. Dr Hughes reported receiving personal fees from Merck outside the submitted work. Dr Simhan reported being the co-founder of Naima Health LLC and receiving personal fees from UpToDate outside the submitted work. Dr Costantine reported relationships with Baxter International, Momenta Pharmaceuticals, Progenity, AMAG Pharmaceuticals, and ObsEva. Dr Tita reported receiving grants from Pfizer for a COVID-19 in pregnancy trial outside the submitted work. No other disclosures were reported.

Funding Support: This work is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (grants UG1 HD087230, UG1 HD027869,UG1 HD027915, UG1 HD034208, UG1 HD040500, UG1 HD040485, UG1 HD053097, UG1HD040544, UG1 HD040545, UG1 HD040560, UG1 HD040512, UG1 HD087192, and U10 HD036801) and the National Center for Advancing Translational Sciences (grant UL1TR001873).

Role of the Funder/Sponsor: The NICHD’s Maternal-Fetal Medicine Units (MFMU) Network is funded by a cooperative agreement between NICHD and the MFMU centers. The NICHD was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review and approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The members of the NICHD’s MFMU Network are listed in Supplement 4.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.