Abstract
This cohort study compares the clinical characteristics and outcomes of hospitalized women who gave birth with and without coronavirus disease 2019.
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.
Methods
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
Results
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).
Table 1. Baseline Characteristics of Pregnant Women Giving Birth by Coronavirus Disease 2019 (COVID-19) Status.
| Characteristic | No. (%) | P value | |
|---|---|---|---|
| Without COVID-19 (n = 400 066) | With COVID-19 (n = 6380) | ||
| Age, mean, y | 29.1 (5.8) | 28.3 (6.2) | <.001 |
| Age, category, y | <.001 | ||
| ≤24 | 92 181 (23.0) | 1897 (29.7) | |
| 25-34 | 233 663 (58.4) | 3368 (52.8) | |
| 35-44 | 73 314 (18.3) | 1097 (17.2) | |
| ≥45 | 908 (0.2) | 18 (0.3) | |
| Race/ethnicity | <.001 | ||
| Black, non-Hispanic | 57 584 (15.0) | 1091 (17.6) | |
| Hispanic | 67 654 (17.7) | 2634 (42.6) | |
| Other/unknown | 38 761 (10.1) | 739 (11.9) | |
| White, non-Hispanic | 218 735 (57.2) | 1723 (27.8) | |
| Black and/or Hispanic | 125 238 (31.3) | 3725 (58.4) | |
| Discharge month | <.001 | ||
| April | 66 056 (16.5) | 778 (12.2) | |
| May | 67 330 (16.8) | 1017 (15.9) | |
| June | 63 684 (15.9) | 948 (14.9) | |
| July | 66 610 (16.6) | 1454 (22.8) | |
| August | 65 442 (16.4) | 1228 (19.2) | |
| September | 53 485 (13.4) | 697 (10.9) | |
| October | 17 307 (4.3) | 252 (3.9) | |
| November | 152 (0.0) | 6 (0.1) | |
| Region | <.001 | ||
| Midwest | 90 994 (22.9) | 982 (15.4) | |
| Northeast | 58 990 (14.8) | 1581 (24.9) | |
| South | 182 971 (46.0) | 3055 (48.0) | |
| West | 65 015 (16.3) | 740 (11.6) | |
| Setting | <.001 | ||
| Urban hospital | 345 776 (86.9) | 5696 (89.6) | |
| Teaching hospital | 191 810 (48.2) | 3706 (58.3) | |
| Trimester | <.001 | ||
| Second | 3420 (0.9) | 88 (1.4) | |
| Third | 393 246 (98.3) | 6243 (97.8) | |
| Missing data | 3400 (0.9) | 49 (0.8) | |
| Comorbidity | |||
| Obesity | 60 428 (15.1) | 1094 (17.1) | <.001 |
| Morbid obesity | 15 925 (4.0) | 289 (4.5) | .03 |
| Hypertension | 19 117 (4.8) | 288 (4.5) | .33 |
| Gestational hypertension | 29 584 (7.4) | 381 (6.0) | <.001 |
| Diabetes | 5716 (1.4) | 132 (2.1) | <.001 |
| Gestational diabetes | 38 066 (9.5) | 667 (10.5) | .01 |
| Pulmonary disease | 24 687 (6.2) | 329 (5.2) | <.001 |
| Smoking | 18 606 (4.7) | 92 (1.4) | <.001 |
| Renal disease | 1073 (0.3) | 27 (0.4) | .02 |
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).
Table 2. In-Hospital Outcomes of Pregnant Women Giving Birth According to Coronavirus Disease 2019 (COVID-19) Status.
| Outcome | No. (%) | P value | Unadjusted OR (95% CI) | Adjusted OR (95% CI)a | |
|---|---|---|---|---|---|
| Without COVID-19 (n = 400 066) | With COVID-19 (n = 6380) | ||||
| Cesarean delivery | 109 865 (27.5) | 1847 (28.9) | .01 | 1.08 (1.02-1.14) | 1.07 (1.02-1.13) |
| Preterm labor | 16 137 (4.0) | 332 (5.2) | <.001 | 1.31 (1.17-1.46) | 1.19 (1.06-1.33) |
| Preterm birthb | 23 234 (5.8) | 459 (7.2) | <.001 | 1.26 (1.14-1.38) | 1.17 (1.06-1.29) |
| Stillbirth | 1289 (0.3) | 34 (0.5) | .003 | 1.66 (1.18-2.33) | 1.23 (0.87-1.75) |
| Preeclampsia | 27 078 (6.8) | 564 (8.8) | <.001 | 1.36 (1.22-1.46) | 1.21 (1.11-1.33) |
| Eclampsia | 288 (0.1) | 8 (0.1) | .12 | 1.74 (0.86-3.52) | 1.56 (0.77-3.16) |
| HELLP syndrome | 989 (0.2) | 33 (0.5) | <.001 | 2.10 (1.48-2.97) | 1.96 (1.36-2.81) |
| Myocardial infarction | 18 (0.0) | 8 (0.1) | <.001 | 27.90 (12.13-64.20) | 30.89 (12.56-75.99) |
| Stroke | 14 (0.0) | 0 | .64 | NA | NA |
| VTE | 268 (0.1) | 15 (0.2) | <.001 | 3.52 (2.09-5.92) | 3.43 (2.01-5.82) |
| Thrombotic eventc | 300 (0.1) | 22 (0.3) | <.001 | 4.61 (2.99-7.11) | 4.47 (2.87-6.96) |
| Intensive care | 1747 (0.4) | 212 (3.3) | <.001 | 7.84 (6.78-9.06) | 6.47 (5.55-7.55) |
| Mechanical ventilation | 212 (0.1) | 86 (1.3) | <.001 | 25.77 (20.03-33.15) | 23.70 (17.95-31.29) |
| Renal replacement therapy | 238 (0.1) | 12 (0.2) | <.001 | NA | NA |
| Chest imagingd | 4122 (1.0) | 748 (11.7) | <.001 | NA | NA |
| Discharge disposition | <.001 | ||||
| Home | 398 388 (99.6) | 6309 (98.9) | NA | NA | |
| Postacute care | 197 (0.0) | 13 (0.2) | NA | NA | |
| Death | 20 (0.0) | 9 (0.1) | 28.26 (12.86-62.08) | 26.07 (11.26-60.38) | |
| Hospice | 74 (0.0) | 1 (0.0) | NA | NA | |
| Other | 1387 (0.3) | 48 (0.8) | NA | NA | |
| Length of stay, mean, d | 2.4 (2.5) | 2.8 (3.4) | <.001 | NA | NA |
| Length of stay, category, d | <.001 | NA | NA | ||
| ≤2 | 267 177 (66.8) | 4099 (64.3) | NA | NA | |
| 3 | 91 690 (22.9) | 1387 (21.7) | NA | NA | |
| >3 | 41 199 (10.3) | 894 (14.0) | NA | NA | |
Abbreviations: HELLP, preeclampsia with hemolysis, elevated liver enzymes, low platelet count; NA, not applicable; OR, odds ratio; VTE, venous thromboembolism.
Adjusted for propensity score, which estimates the probability of COVID-19 as a function of 15 baseline covariates: age, race/ethnicity, geographic region, urban population, teaching hospital, discharge month, trimester, hypertension, gestational hypertension, diabetes, gestational diabetes, kidney disease, pulmonary disease, tobacco use, and obesity. The propensity score was defined as the logit of the predicted probability of COVID-19 status.
Preterm birth was defined as preterm labor with childbirth, premature rupture of membranes with subsequent childbirth, preterm newborn, or a newborn with a very low birth weight.
Thrombotic event was defined as the composite of myocardial infarction, ischemic stroke, venous thromboembolism, or arterial thrombosis.
Chest imaging included radiography, computed tomography, and computed tomography angiography of the chest.
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.
Discussion
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.
eMethods
eTable 1. ICD-10 Diagnosis Codes for Comorbidities
eTable 2. ICD-10 Diagnosis and Procedure Codes and Billing Codes for In-Hospital Outcomes.
References
- 1.Chen Y-H, Keller J, Wang I-T, Lin C-C, Lin H-C. Pneumonia and pregnancy outcomes: a nationwide population-based study. Am J Obstet Gynecol. 2012;207(4):288.e1-288.e7. doi: 10.1016/j.ajog.2012.08.023 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Adhikari EH, Moreno W, Zofkie AC, et al. Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection. JAMA Netw Open. 2020;3(11):e2029256. doi: 10.1001/jamanetworkopen.2020.29256 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Rosenthal N, Cao Z, Gundrum J, Sianis J, Safo S. Risk factors associated with in-hospital mortality in a US national sample of patients with COVID-19. JAMA Netw Open. 2020;3(12):e2029058. doi: 10.1001/jamanetworkopen.2020.29058 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Vandenbroucke JP, von Elm E, Altman DG, et al. ; STROBE initiative . Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Ann Intern Med. 2007;147(8):W163-94. doi: 10.7326/0003-4819-147-8-200710160-00010-w1 [DOI] [PubMed] [Google Scholar]
- 5.Zambrano LD, Ellington S, Strid P, et al. ; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team . Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647. doi: 10.15585/mmwr.mm6944e3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Knight M, Bunch K, Vousden N, et al. ; UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group . Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ. 2020;369:m2107. doi: 10.1136/bmj.m2107 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods
eTable 1. ICD-10 Diagnosis Codes for Comorbidities
eTable 2. ICD-10 Diagnosis and Procedure Codes and Billing Codes for In-Hospital Outcomes.