In-Hospital Mortality in a Cohort of Hospitalized Pregnant and Nonpregnant Patients With COVID-19
Authors: Beth L. Pineles, Katherine E. Goodman, Lisa Pineles, Lyndsay M. O’Hara, Gita Nadimpalli, Laurence S. Magder, Jonathan D. Baghdadi, Jacqueline G. Parchem, Anthony D. Harris
Journal: Annals of Internal Medicine (2021)

Letters11 May 2021In-Hospital Mortality in a Cohort of Hospitalized Pregnant and Nonpregnant Patients With COVID-19FREEBeth L. Pineles, MD, PhD, Katherine E. Goodman, JD, PhD, Lisa Pineles, MA, Lyndsay M. O’Hara, PhD, MPH, Gita Nadimpalli, MD, MPH, Laurence S. Magder, PhD, Jonathan D. Baghdadi, MD, PhD, Jacqueline G. Parchem, MD, Anthony D. Harris, MD, MPHBeth L. Pineles, MD, PhDMcGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TexasSearch for more papers by this author, Katherine E. Goodman, JD, PhDThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Lisa Pineles, MAThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Lyndsay M. O’Hara, PhD, MPHThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Gita Nadimpalli, MD, MPHThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Laurence S. Magder, PhDThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Jonathan D. Baghdadi, MD, PhDThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this author, Jacqueline G. Parchem, MDMcGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TexasSearch for more papers by this author, Anthony D. Harris, MD, MPHThe University of Maryland School of Medicine, Baltimore, MarylandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0974 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Studies examining pregnant patients with COVID-19 have shown an increased risk for death in pregnant versus nonpregnant patients of reproductive age (1). However, these data are based on registries that are limited by a significant proportion of missing data, including pregnancy status, and likely have biased case ascertainment.Objective: To evaluate the risk for in-hospital death among pregnant and nonpregnant patients of reproductive age hospitalized with COVID-19, because studies with more thorough ascertainment of COVID-19 in pregnancy are needed to provide the foundation for clinical management and health care policy.Methods and Findings: We did a retrospective cohort study of patients in the Premier Healthcare Database, an all-payer data repository that captures 20% of U.S. hospitalizations. We included all female inpatients aged 15 to 45 years hospitalized from April to November 2020 with COVID-19. A patient was defined as pregnant if the encounter included any pregnancy-related diagnosis. This study did not include personally identifiable information and was exempted from review by the institutional review board of the University of Maryland, Baltimore.To exclude asymptomatic patients with COVID-19 diagnoses due to positive results on screening tests, we used only patients with a viral pneumonia diagnosis (Supplement Table). We then did sensitivity analyses using subgroups of patients with an intensive care unit admission or mechanical ventilation.Analyses were done using SAS, version 9.4 (SAS Institute). The Supplement provides detailed methods.The cohort consisted of 1062 pregnant and 9815 nonpregnant patients hospitalized with COVID-19 and viral pneumonia. Pregnant patients were younger and more likely to have public insurance than nonpregnant patients (Table 1) (2) Pregnant patients were also less likely to have most comorbid conditions, including hypertension, chronic pulmonary disease, diabetes, and obesity.Table 1 Characteristics and Outcomes Among Patients With COVID-19 and Viral Pneumonia DiagnosesIn-hospital death occurred in 0.8% (n = 9) of pregnant patients and 3.5% (n = 340) of nonpregnant patients hospitalized with COVID-19 and viral pneumonia (Table 1). Median time from admission to death was 18 days (interquartile range, 6 to 28 days) for pregnant patients and 12 days (interquartile range, 5 to 23 days) for nonpregnant patients. Among the subgroup of patients admitted to an intensive care unit, in-hospital mortality was 3.5% (9 of 255) in pregnant patients and 14.9% (283 of 1898) in nonpregnant patients. Among those who received mechanical ventilation, in-hospital death occurred in 8.6% (9 of 105) of pregnant patients and 31.4% (294 of 937) of nonpregnant patients.Pregnant patients who died are described in Table 2. Their ages ranged from 23 to 44 years. Eight were non-Hispanic Black or Hispanic. All died between April and July. Six were obese, and 7 had at least 1 comorbid condition. Gestational ages ranged from 23 to 39 weeks, and 7 of 9 deliveries were live births.Table 2 Characteristics of Pregnant Patients With In-Hospital MortalityDiscussion: Overall and within multiple subgroups, we found a substantially lower rate of in-hospital mortality in pregnant patients than nonpregnant patients hospitalized with COVID-19 and viral pneumonia. The rates found in this study are consistent with results of multiple other studies (3, 4). A cohort study including all symptomatic patients with COVID-19 aged 20 to 39 years hospitalized throughout the United Kingdom reported mortality of 0.8% in pregnant and 3.1% in nonpregnant persons (3).Our study suggests lower mortality among pregnant patients than was initially reported. Using data collected from a voluntary reporting registry, the U.S. Centers for Disease Control and Prevention observed a mortality rate of 0.15% among pregnant and 0.12% among nonpregnant patients, including both hospitalized and nonhospitalized patients (1). That study was limited in that pregnancy status was available for only 36% of patients, creating potential for case ascertainment bias (1).A strength 7of our study is the use of a large database including patient discharge data from 853 hospitals. It is hospital-based, providing a clearly defined population without the biases of registry-based studies. However, some amount of collider bias is expected because both severity of disease and pregnancy affect the likelihood of hospitalization.Other limitations include the small number of deaths, with resultant lack of adjustment for confounding. Results cannot be extrapolated to patients who are not hospitalized. Laboratory test results were unavailable, but prior research showed a strong correlation between COVID-19 diagnosis and laboratory-confirmed SARS-CoV-2 infection (5).In this large, geographically diverse cohort of reproductive-aged patients hospitalized with COVID-19, we found that in-hospital mortality was low in pregnant patients.References1. 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;69:1641-1647. [PMID: 33151921] doi:10.15585/mmwr.mm6944e3 CrossrefMedlineGoogle Scholar2. Elixhauser A, Steiner C, Harris DR, et al. Comorbidity measures for use with administrative data. Med Care. 1998;36:8-27. [PMID: 9431328] CrossrefMedlineGoogle Scholar3. Knight M, Ramakrishnan R, Bunch K, et al. Females in hospital with SARS-CoV-2 infection, the association with pregnancy and pregnancy outcomes: a UKOSS/ISARIC/CO-CIN investigation. Scientific Advisory Group for Emergencies; 2021. Google Scholar4. Metz TD, Clifton RG, Hughes BL, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Disease severity and perinatal outcomes of pregnant patients with coronavirus disease 2019 (COVID-19). Obstet Gynecol. 2021;137:571-580. [PMID: 33560778] doi:10.1097/AOG.0000000000004339 CrossrefMedlineGoogle Scholar5. Kadri SS, Gundrum J, Warner S, et al. Uptake and accuracy of the diagnosis code for COVID-19 among US hospitalizations. JAMA. 2020;324:2553-2554. [PMID: 33351033] doi:10.1001/jama.2020.20323 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment José H. Pagliery, M.D., FACPCitrus Health Network/Florida International University Herbert Wertheim College of Medicine12 May 2021 Are the two study groups comparable? The authors compared two groups of hospitalized women with viral pneumonia who had Covid19. The title of the article suggests that the comparison was between pregnant and non pregnant women. I would like to point out that the non pregnant women were predominantly older and had more comorbidities. Were these differences in age and comorbidities statistically significant? Beth Pineles, Anthony HarrisUTHealth and University of Maryland School of Medicine14 May 2021 Authors' Response We thank the reader for the attention to our manuscript. The differences in age and comorbidities were statistically significant. Due to the small number of events, we did not adjust for these confounders but plan to provide an adjusted analysis in a future, larger paper. Beth Pineles, Anthony HarrisUTHealth and University of Maryland School of Medicine18 May 2021 Authors' Response We thank the reader for the attention to our paper. The writer is correct that the severity of disease is not accounted for and difficult to measure in an administrative dataset. We welcome theories about the cause of the difference in in-hospital mortality between the groups. It is certainly likely that severity of disease as well as differential treatment of pregnant women contribute to the difference in in-hospital mortality we found. Different SpO2 thresholds are used for pregnant patients, which is why we did not choose supplemental oxygen as a grouping variable. However, among mechanically ventilated patients, non-pregnant women were more likely to die (31.4%) than were pregnant women (8.6%), despite no difference in the proportion of mechanically ventilated patients between groups. Given the invasive nature of mechanical ventilation and frequent need for sedation and paralysis in this young group of patients, our experience is that physicians are reluctant to place pregnant patients on mechanical ventilation, despite the need for higher oxygenation thresholds (95% versus 92% oxygen saturation). Thus, we do not believe that the better outcomes observed in pregnant women in the current study are completely explained by a less severe spectrum of disease, and by prioritization of interventions in pregnant women. Federico PrefumoDepartment of Clinical and Experimental Sciences, University of Brescia, Italy17 May 2021 Better care in pregnant women with COVID-19 pneumonia? This interesting paper contradicts previous reports suggesting a higher risk of adverse outcomes in pregnant women with COVID-19 disease matched to non-pregnant (1) and to pregnant (2) women. However, the study suffers from one fundamental bias: it is based on administrative data of women admitted to hospital for COVID-19 pneumonia, and the analysis does not take into account the clinical severity of the disease. It is likely that lower thresholds for hospital admission, intensive care unit admission and mechanical ventilation were applied to the pregnant population. This is due to concerns for fetal wellbeing, as well as to the social appreciation of pregnant women as a group deserving priority in healthcare resources allocation. Just as an example, most guidelines/expert opinions/protocols recommend higher target SpO2 values in pregnant women than in other adult patients. Therefore, it is highly possible that the better outcomes observed in pregnant women in the current study may be explained by a less severe spectrum of disease, and by prioritization of interventions in pregnant women. Martinez-Portilla RJ, Sotiriadis A, Chatzakis C, Torres-Torres J, Espino Y Sosa S, Sandoval-Mandujano K, Castro-Bernabe DA, Medina-Jimenez V, Monarrez-Martin JC, Figueras F, Poon LC. Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx). Ultrasound Obstet Gynecol 2021;57:224-231. Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, Roggero P, Prefumo F, do Vale MS, Cardona-Perez JA, Maiz N, Cetin I, Savasi V, Deruelle P, Easter SR, Sichitiu J, Soto Conti CP, Ernawati E, Mhatre M, Teji JS, Liu B, Capelli C, Oberto M, Salazar L, Gravett MG, Cavoretto PI, Nachinab VB, Galadanci H, Oros D, Ayede AI, Sentilhes L, Bako B, Savorani M, Cena H, García-May PK, Etuk S, Casale R, Abd-Elsalam S, Ikenoue S, Aminu MB, Vecciarelli C, Duro EA, Usman MA, John-Akinola Y, Nieto R, Ferrazi E, Bhutta ZA, Langer A, Kennedy SH, Papageorghiou AT. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr 2021 Apr 22:e211050. doi: 10.1001/jamapediatrics.2021.1050. SEIKH JAHANGIR ALAMConsultant Physician (Private Practice) Vill-Santipur, Post- Meched, Dist- Purba Medinipur, State- West Bengal, PIN-721137, INDIA23 May 2021 Is it not imbalance comparison? In the pregnancy period, different physiological changes occur. As per my opinion, body response to any kind of infection may differ in pregnancy and non pregnancy state. So, how far will the comparison be justifiable ? Disclosures: I declare that I don't have competing interests. Beth Pineles, Anthony HarrisUTHealth and University of Maryland School of Medicine25 May 2021 Authors' Response We thank the reader for this comment. We felt the need to examine this comparison because other authors had reported increased severity of disease and mortality in pregnant women and wanted to confirm this result. When we found a different result showing that pregnant women with COVID did not have an increased risk to non-pregnant women, we felt it was important to disseminate this information because stress and anxiety are already increased among pregnant women during this pandemic. Despite our publication, the popular narrative continues to be that pregnant women are at greater risk than non-pregnant women. Author, Article, and Disclosure InformationAuthors: Beth L. Pineles, MD, PhD; Katherine E. Goodman, JD, PhD; Lisa Pineles, MA; Lyndsay M. O’Hara, PhD, MPH; Gita Nadimpalli, MD, MPH; Laurence S. Magder, PhD; Jonathan D. Baghdadi, MD, PhD; Jacqueline G. Parchem, MD; Anthony D. Harris, MD, MPHAffiliations: McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TexasThe University of Maryland School of Medicine, Baltimore, MarylandDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-0974.Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Pineles (e-mail, beth.l.pineles@uth.tmc.edu). Data set: Available from Premier (www.premierinc.com).Corresponding Author: Anthony D. Harris, MD, MPH, University of Maryland School of Medicine, 10 South Pine Street, MSTF 330, Baltimore, MD 21201; e-mail, aharris@som.umaryland.edu.This article was published at Annals.org on 11 May 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIn-Hospital Mortality in a Cohort of Hospitalized Pregnant and Nonpregnant Patients With COVID-19 José H. Pagliery In-Hospital Mortality in a Cohort of Hospitalized Pregnant and Nonpregnant Patients With COVID-19 Beth L. Pineles , Anthony D. 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Pagliery, MDSociety for Maternal-Fetal Medicine Special Statement: COVID-19 research in pregnancy: progress and potentialOutcomes and proportions of pregnant women during the first and consecutive waves of coronavirus disease 2019: observational cohort studyMaternal COVID-19 Vaccination and Its Potential Impact on Fetal and Neonatal DevelopmentOutcomes of SARS-CoV-2 infected pregnancies after medically assisted reproduction August 2021Volume 174, Issue 8 Page: 1186-1188 ePublished: 11 May 2021 Issue Published: August 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...