Association of SARS-CoV-2 Infection With Serious Obstetric Complications
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
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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Additional Info
Disclosure statements are available on the authors' profiles:
Association of SARS-CoV-2 Infection With Serious Maternal Morbidity and Mortality From Obstetric Complications
JAMA 2022 Feb 07;[EPub Ahead of Print], TD Metz, RG Clifton, BL Hughes, GJ Sandoval, WA Grobman, GR Saade, TA Manuck, M Longo, A Sowles, K Clark, HN Simhan, DJ Rouse, H Mendez-Figueroa, C Gyamfi-Bannerman, JL Bailit, MM Costantine, HM Sehdev, ATN Tita, GA MaconesFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The study by Metz et al adds to the body of evidence that demonstrates the risk of SARS-CoV-2 infection in pregnancy. While data previously demonstrated that SARS-CoV-2 infection increases mortality and morbidity attributed to infection with the virus,1-3 this study demonstrates that SARS-CoV-2 contributes to increased mortality and morbidity from conditions other than infection with the virus itself.
Maternal mortality and morbidity is at an unacceptably high level in the United States, and addressing this crisis is a national priority. Importantly, maternal mortality has increased since the beginning of the pandemic. Although the causes are not delineated, the number of maternal deaths rose from 658 in 2018 to 861 in 2020.4 In Metz’s study, all five maternal deaths were in the SARS-CoV-2 group. The largest contributors of maternal mortality in the United States are hypertensive disorders of pregnancy, postpartum hemorrhage, and sepsis.5 Thus, it is particularly relevant that the primary outcome in this study included serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. Although the Metz study found no significant interaction between race or ethnicity and SARS-CoV-2 infection for any of the outcomes, racial disparities of maternal mortality and morbidity should not be underestimated; the CDC data demonstrates that the maternal death rate for Blacks is nearly triple that of Whites.4
Much has changed since the first and second waves of the COVID-19 pandemic—the time analyzed during this study. Most notably is the development and availability of COVID-19 vaccines which protect against contracting the virus and against serious adverse outcomes among those that do become infected.6 This is germane to the Mertz et al study, which demonstrated that patients with moderate or higher disease severity had worse outcomes, and outcomes for those with mild or no symptoms were not significantly different from those without SARS-CoV-2 infection. Similar findings were observed for neonatal outcomes. Despite advocacy by many professional organizations7, none of the COVID vaccines have been tested in pregnant patients. Nonetheless, as of January 2022, no safety concerns have been observed in pregnant women enrolled in the CDC’s v-safe post-vaccination health checker,8 and compared with unvaccinated patients, COVID-19 vaccination during pregnancy was not associated with pregnancy complications.9 Additionally, vaccinated patients have been shown to produce higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy, and vaccine-generated antibodies were present in umbilical cord blood and breast milk following maternal vaccination, suggesting fetal and infant benefits.10,11 Although vaccination rates are increasing, vaccine hesitancy remains high with only 67% of all pregnant patients and 53% of Black pregnant patients being vaccinated in the United States as of February 2022.12 Obstetric care clinicians must continue to encourage patients to receive COVID-19 vaccination and work to improve access for underserved population.
In addition to vaccination, treatment options have improved since 2020. Although obstetric care clinicians may consider the use of the oral SARS-CoV-2 protease inhibitor for the treatment of non-hospitalized SARS-CoV-2 positive pregnant patients with mild to moderate symptoms, particularly those at high risk, availability of this treatment is limited. Furthermore, monoclonal antibodies, once thought to be promising, are generally ineffective against the Omicron variant, which is currently the most prevalent SARS-CoV-2 variant.13
References