Physiologic adaptations and changes in immune regulation may increase the risk of morbidity and mortality in pregnant women with respiratory infections.1,2 The effects of coronavirus disease 2019 (COVID-19) in pregnancy have not been fully delineated. We compared the clinical characteristics and outcomes of hospitalized women who gave birth with and without COVID-19.
Women giving birth and discharged between April 1 and November 23, 2020, were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes within the Premier Healthcare Database, an all-payer database encompassing approximately 20% of US hospitalizations.3 Race and ethnicity were self-reported, and COVID-19 status (ICD-10 code U07.1), comorbidities, and in-hospital outcomes were identified using ICD-10 and billing codes (eTables 1 and 2 in the Supplement). Discharge disposition and in-hospital death were reported in all patients.
Data were collected and deidentified by Premier Inc, which curates the Premier Healthcare Database, then analyzed at Brigham and Women’s Hospital in Boston, Massachusetts. The Mass General Brigham Institutional Review Board approved the study protocol and waived the requirement for patient informed consent. Multivariable logistic regression was used to derive a propensity model estimating the probability of COVID-19 (eMethods in the Supplement). Associations between COVID-19 and in-hospital outcomes were examined using propensity score-adjusted regression. Factors associated with in-hospital death or mechanical ventilation use among pregnant women with COVID-19 were identified using forward stepwise logistic regression (eMethods in the Supplement). Analyses were conducted using Stata, version 15.0 (Stata Corp) with a 2-tailed P value less than .05 considered significant. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.4
Among the 406 446 women hospitalized for childbirth over the 8 months of the study, 6380 (1.6%) had COVID-19. Compared with pregnant women without COVID-19 (n = 400 066), the women with COVID-19 were younger and more often Black and/or Hispanic and with diabetes and obesity (Table 1).
Of the 6380 women with COVID-19 who gave birth, 6309 (98.9%) were discharged to home, 212 (3.3%) needed intensive care, 86 (1.3%) needed mechanical ventilation, and 9 (0.1%) died in the hospital (Table 2). Although in-hospital mortality was low, it was significantly higher in the women with COVID-19 than in those without COVID-19 (141 [95% CI, 65-268] vs 5.0 [95% CI, 3.1-7.7] deaths per 100 000 women). Rates of myocardial infarction and venous thromboembolism (VTE) were higher in the women with COVID-19 who gave birth than in those without COVID-19 (myocardial infarction: 0.1% vs 0.004%; VTE: 0.2% vs 0.1%; P < .001). COVID-19 was associated with higher odds of preeclampsia (adjusted odds ratio [aOR], 1.21 [95% CI, 1.11-1.33]) and preterm birth (aOR, 1.17 [95% CI, 1.06-1.29]) but not with significantly higher odds of stillbirth (aOR, 1.23 [95% CI, 0.87-1.75]). Use of chest imaging, intensive care treatment, and mechanical ventilation was higher among the women who gave birth with COVID-19 compared with those without COVID-19 (Table 2).
Among women with COVID-19 who gave birth, age (OR, 1.91 [95% CI, 1.31-2.77] per 10 years), morbid obesity (OR, 3.85 [95% CI, 2.05-7.21]), diabetes (OR, 4.51 [95% CI, 2.10-9.70]), kidney disease (OR, 21.57 [95% CI, 7.73-60.10]), eclampsia (OR, 116.1 [95% CI, 22.91-588.50]), thrombotic events (OR, 45.10 [95% CI, 17.13-118.8]), and stillbirth (OR, 7.88 [95% CI, 2.39-25.98]) were associated with higher odds of mechanical ventilation use or in-hospital death.
In a large national cohort of US women hospitalized for childbirth, we found that absolute rates of death and adverse events in those diagnosed with COVID-19 were low, as might be expected in a young population in whom the disease may have been detected incidentally. Although the absolute risk differences were small, in-hospital death, VTE, and preeclampsia were considerably higher among women who gave birth with COVID-19 than in those without COVID-19. The present findings confirm previously reported mortality rates and indicate a higher risk of VTE in women diagnosed with COVID-19 in the setting of childbirth.5,6 Limitations include potential misclassification by ICD-10 codes, lack of confirmatory testing and imaging findings, information on disease severity, the inability to distinguish asymptomatic from symptomatic COVID-19 cases, low event rates, and residual confounding.
The higher rates of preterm birth, preeclampsia, thrombotic events, and death in women giving birth with COVID-19 highlight the need for strategies to minimize risk. As studies investigating therapies for COVID-19 have largely excluded pregnant women, the data also underscore the importance of including this population in clinical trials of treatments and vaccines.
Accepted for Publication: December 29, 2020.
Published Online: January 15, 2021. doi:10.1001/jamainternmed.2020.9241
Corresponding Author: Scott D. Solomon, MD, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (firstname.lastname@example.org).
Author Contributions: Drs Jering and Solomon 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: Jering, Cunningham, Claggett.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Jering, Solomon.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Jering, Claggett, Cunningham, Greene.
Obtained funding: Solomon.
Administrative, technical, or material support: Jering.
Conflict of Interest Disclosures: Dr Jering reports being supported by a postdoctoral training grant from the National Heart, Lung, and Blood Institute (NHLBI) (T32HL007604). Dr Claggett reports receiving personal fees from Amgen, Boehringer Ingelheim, Corvia Medical, MyoKardia, and Novartis outside the submitted work. Dr Cunningham reports being supported by a postdoctoral training grant from NHLBI (T32HL094301). Dr Rosenthal reports being an employee of Premier Inc, which curates the Premier Healthcare Database used in this study. Dr Vardeny reports receiving research support from NHLBI, grant support from AstraZeneca and Bayer, and personal fees from the American Heart Association, Novartis, and Sanofi Pasteur outside the submitted work. Dr Solomon reports receiving grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead Sciences, GlaxoSmithKline, Ionis Pharmaceuticals, LoneStar Heart, Mesoblast, MyoKardia, NeuroTronik, NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos, as well as personal fees from Abbott, Actelion, Akros, Alnylam Pharmaceuticals, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior Pharmaceuticals, Cardurion Pharmaceuticals, Corvia Medical, Cytokinetics, Daiichi Sankyo, Gilead Sciences, GlaxoSmithKline, Ironwood Pharmaceuticals, Eli Lilly, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion Pharmaceuticals, AOBiome, Janssen, Cardiac Dimensions, Sanofi Pasteur, Tenaya, DiNAQOR, Tremeau Pharmaceuticals, CellProthera, and Moderna outside the submitted work. No other disclosures were reported.
Additional Contributions: We thank Muthiah Vaduganathan, MD, MPH, and Ankeet Bhatt, MD, of Brigham and Women’s Hospital for their thoughtful contributions to the study design and revisions of this article. They were not compensated for their contributions.
Additional Information: Qualified researchers can apply for data access directly to Premier Inc.
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