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. 2022 Feb 22;327(8):748-759.
doi: 10.1001/jama.2022.1190.

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

Torri D Metz  1 , Rebecca G Clifton  2 , Brenna L Hughes  3 , Grecio J Sandoval  2 , William A Grobman  4 , George R Saade  5 , Tracy A Manuck  3 , Monica Longo  6 , Amber Sowles  1 , Kelly Clark  3 , Hyagriv N Simhan  7 , Dwight J Rouse  8 , Hector Mendez-Figueroa  9 , Cynthia Gyamfi-Bannerman  10 , Jennifer L Bailit  11 , Maged M Costantine  12 , Harish M Sehdev  13 , Alan T N Tita  14 , George A Macones  15 ; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network
Collaborators, Affiliations

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

Torri D Metz et al. JAMA. .

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Cohort Development in a Study of SARS-CoV-2 Infection Among Pregnant and Postpartum Individuals
Bpm indicates beats per minute; Fio2, fraction of inspired oxygen; and Spo2, oxygen saturation as measured by pulse oximetry. aFirst positive SARS-CoV-2 test result (molecular or antigen). bIncludes patients with no positive SARS-CoV-2 result any time during pregnancy through 42 days postpartum in the inpatient or outpatient setting. cCOVID-19 severity classification based on data during pregnancy through 42 days postpartum defined by National Institutes of Health guidelines for disease severity. Multiple signs and symptoms may be listed for each patient. dRespiratory failure is use of any of the following: extracorporeal membrane oxygenation, continuous positive airway pressure, bilevel positive airway pressure, or ventilation. eMultiple organ dysfunction or failure is 2 or more of the following: cardiac arrest, impaired liver function, kidney insufficiency (serum creatinine >1.2 mg/dL), kidney failure requiring dialysis, encephalopathy, any need for pressor support, or thrombocytopenia (platelets <100 000/μL). fOther symptoms include fever, fatigue, chills, back pain, nausea, vomiting, joint pain, conjunctivitis, confusion, diarrhea, or other. Symptoms are not mutually exclusive.
Figure 2.
Figure 2.. Maternal Outcomes Stratified by COVID-19 Severity
NA indicates not applicable. aIncludes eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; pulmonary edema; severe hypertension (blood pressure at least 160/110 mm Hg) with acute administration of antihypertensive medication; hepatic rupture; impaired liver function (blood concentrations of liver enzymes 2 times the upper limit of normal); kidney insufficiency (serum creatinine at least 1.2 mg/dL); thrombocytopenia (platelets <100 000/μL); or placental abruption. bIncludes transfusion of 4 or more units of packed red blood cells and surgical or radiologic interventions to control bleeding and related complications (eg, uterine packing, intrauterine balloon tamponade, uterine artery ligation, uterine compression sutures, hysterectomy, laparotomy, evacuation of hematoma, arterial embolization, and uterine evacuation). cIncludes sepsis (infection with organ dysfunction), bacteremia, endometritis requiring intravenous antibiotic therapy for more than 24 hours, deep incisional surgical site infection, or pelvic abscess. dAmerican College of Obstetricians and Gynecologists (ACOG) and Society for Maternal-Fetal Medicine (SMFM)–defined severe morbidity and mortality includes death from any cause, intensive care unit (ICU) admission, or transfusion of 4 or more units of blood.
Figure 3.
Figure 3.. Neonatal Outcomes Stratified by COVID-19 Severity
aStatistical comparisons were not made for subcategories of prespecified outcomes. Data for subcategories are presented for descriptive purposes.
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