Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic | Pediatrics | JAMA Network Open | JAMA Network
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Table 1.  Demographic and Clinical Characteristics of Hospitalized Women Undergoing Childbirth With and Without COVID-19
Demographic and Clinical Characteristics of Hospitalized Women Undergoing Childbirth With and Without COVID-19
Table 2.  Clinical Outcomes of Hospitalized Women Undergoing Childbirth With and Without COVID-19
Clinical Outcomes of Hospitalized Women Undergoing Childbirth With and Without COVID-19
Table 3.  Gestational Age and Associated Mortality of Hospitalized Women Undergoing Childbirth With and Without COVID-19
Gestational Age and Associated Mortality of Hospitalized Women Undergoing Childbirth With and Without COVID-19
1.
Mullins  E, Evans  D, Viner  RM, O’Brien  P, Morris  E.  Coronavirus in pregnancy and delivery: rapid review.   Ultrasound Obstet Gynecol. 2020;55(5):586-592. doi:10.1002/uog.22014PubMedGoogle ScholarCrossref
2.
Jering  KS, Claggett  BL, Cunningham  JW,  et al.  Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.   JAMA Intern Med. 2021;181(5):714-717. doi:10.1001/jamainternmed.2020.9241PubMedGoogle ScholarCrossref
3.
Elshafeey  F, Magdi  R, Hindi  N,  et al.  A systematic scoping review of COVID-19 during pregnancy and childbirth.   Int J Gynaecol Obstet. 2020;150(1):47-52. doi:10.1002/ijgo.13182PubMedGoogle ScholarCrossref
4.
Di Mascio  D, Khalil  A, Saccone  G,  et al.  Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.   Am J Obstet Gynecol MFM. 2020;2(2):100107. doi:10.1016/j.ajogmf.2020.100107PubMedGoogle Scholar
5.
Villar  J, Ariff  S, Gunier  RB,  et al.  Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID multinational cohort study.   JAMA Pediatr. 2021. doi:10.1001/jamapediatrics.2021.1050PubMedGoogle Scholar
6.
Allotey  J, Stallings  E, Bonet  M,  et al; for PregCOV-19 Living Systematic Review Consortium.  Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.   BMJ. 2020;370:m3320. doi:10.1136/bmj.m3320PubMedGoogle Scholar
7.
World Health Organization.  International Statistical Classification of Diseases, Tenth Revision (ICD-10). World Health Organization; 1992.
8.
Nguyen  NT, Chinn  J, Nahmias  J,  et al.  Outcomes and mortality among adults hospitalized with COVID-19 at US Medical Centers.   JAMA Netw Open. 2021;4(3):e210417. doi:10.1001/jamanetworkopen.2021.0417PubMedGoogle Scholar
9.
Janevic  T, Glazer  KB, Vieira  L,  et al.  Racial/ethnic disparities in very preterm birth and preterm birth before and during the COVID-19 pandemic.   JAMA Netw Open. 2021;4(3):e211816. doi:10.1001/jamanetworkopen.2021.1816PubMedGoogle Scholar
10.
Kuehn  B.  Disparities in maternal mortality.   JAMA. 2019;322(16):1545. doi:10.1001/jama.2019.16156PubMedGoogle Scholar
11.
Webb Hooper  M, Nápoles  AM, Pérez-Stable  EJ.  COVID-19 and racial/ethnic disparities.   JAMA. 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598PubMedGoogle ScholarCrossref
12.
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.2020.29256PubMedGoogle Scholar
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    2 Comments for this article
    EXPAND ALL
    COVID-19 Vaccination in Pregnancy: Evidence-based and Much Needed
    Raffaela Schiavon, MD, Ob/Gyn | Ipas México, México
    It is essential to use good evidence to promote vaccination among pregnant women: evidence that shows the effect of COVID-19 on pregnant persons and their developing child, as well as evidence about the safety of vaccines among them.

    But it is also essential to include pregnant women in all next clinical trials for new drugs and new vaccines, as long as sufficient animal data on embryotoxicology are provided. Pregnant women should be able to decide whether to voluntarily participate in such clinical protocols. They should be given moral and ethical authority to do so, as well as the option
    to terminate a pregnancy in case new evidence arises about potential risk to the embryo/fetus. Probably, reluctance to include pregnant women in research stems more from liability fears and moral hesitancy toward abortion than from true concerns about women´s health.

    Excluding them from trials is not a way to protect them from harm; it's a way to exclude them from the benefits of scientific progress.

    CONFLICT OF INTEREST: I belong to the Mexican Expert Group (GTAV) analyzing evidence to establish national vaccination priorization strategy in the context of vaccine scarcity.
    READ MORE
    Pregnancy Outcomes Associated With COVID-19: At Odds with Odds Ratios and Confounding
    Dr Annette Regan, PhD | University of San Francisco
    In this article, the authors used an impressively large database to evaluate the association between COVID-19 diagnosis at delivery hospitalization and the risk of a range of adverse pregnancy outcomes. While valuable to have data from such a large population, several aspects of the study raise concern regarding the validity of the results.

    First, the authors report stark differences in COVID-19 diagnoses by age, race/ethnicity, and chronic health conditions. These factors are also known risk factors for severe maternal morbidity and mortality and other adverse pregnancy outcomes. Despite this, the authors describe no efforts to adjust for potential
    confounding bias by these factors. The reported odds ratio is likely to be a biased over-estimate of the true effect of COVID-19 on mortality. Furthermore, adjustment for the joint effect of multiple confounders is likely to attenuate this association.

    Second, the authors chose to model odds ratios rather than risk ratios, which are a more appropriate measure of association for use in cohort studies. Although odds ratios will approximate risk ratios in scenarios with low incidence outcomes (<10%), known as the “rare disease assumption,” odds ratios over-estimate risk ratios when this criterion is not met. While in-hospital mortality and ICU admission likely meet requirements for the rare disease assumption in this study (≤5%), their outcome ‘discharge status’ does not. For example, the odds of discharge to home was reported as 0.47 times lower among COVID-infected compared to uninfected pregnant persons; however, estimation of a relative risk indicates that the unadjusted risk of discharge to home is 0.99.

    Finally, this study exclusively relied on diagnostic coding from the hospital record at the time of birth, which will exclude asymptomatic women with COVID-19 and women infected earlier in pregnancy. From my own work, I have found that reliance on administrative codes exclusively will miss approximately 19% of all COVID-19 cases during pregnancy (asymptomatic and symptomatic). In this study, this could have resulted in 3,555 additional COVID-19 cases misclassified as unexposed. Since detection is more likely for those with severe symptoms (in the absence of screening), it is likely that observed cases represent those with more severe symptoms. It is worth underscoring that the presented results reflect the association between mortality and symptomatic COVID-19 near delivery – not SARS-CoV-2 infection during pregnancy.

    I agree with the authors that a link between SARS-CoV-2 infection and maternal mortality is highly plausible. However, given the large size of this study, the influence of these biases can have wide-scale implications if not appropriately considered in systematic reviews and meta-analyses. I'd like to thank the authors for taking on such an important area of research, but would also like to caution readers from over-interpreting biased odds ratios.

    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    Obstetrics and Gynecology
    August 11, 2021

    Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic

    Author Affiliations
    • 1University of California, Irvine Medical Center, Orange
    • 2Vizient, Centers for Advanced Analytics, Chicago, Illinois
    JAMA Netw Open. 2021;4(8):e2120456. doi:10.1001/jamanetworkopen.2021.20456
    Key Points

    Question  What are the characteristics and outcomes associated with giving birth with COVID-19 over the first year of the pandemic in the US?

    Findings  This cohort study examines 869 079 adult women, including 18 715 women with COVID-19, who underwent childbirth at 499 US medical centers between March 1, 2020, and February 28, 2021. Women with COVID-19 had increased mortality, need for intubation and ventilation, and intensive care unit admission.

    Meaning  These findings suggest that COVID-19 was associated with increased risk of morbidity and mortality for women giving birth.

    Abstract

    Importance  Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed.

    Objective  To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19.

    Design, Setting, and Participants  This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021.

    Exposures  The presence of a COVID-19 diagnosis using ICD-10.

    Main Outcomes and Measures  Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2.

    Results  Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non–COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25]; P < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P < .001), and in-hospital mortality (24 women [0.1%] vs 71 [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001).

    Conclusions and Relevance  This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.

    Introduction

    Although there has been extensive research on COVID-19 since its initial emergence, the broad range of perinatal COVID-19 outcomes continues to emerge.1 A study by Jering and colleagues2 reported the largest US cohort, to date, including 6380 women with COVID-19 giving birth, and found that the absolute death rates in women with COVID-19 were considerably higher than in women without COVID-19. They also found higher rates of preterm birth, preeclampsia, and thrombotic events.2 Prior studies on the effects of COVID-19 on pregnancy have reported higher rates of cesarean delivery, preterm birth, and maternal morbidity and mortality index scores.3-5 As the COVID-19 pandemic has progressed, mortality and outcomes in the general population have improved.6 The aim of this study was to examine the characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19 during the first year of the pandemic, examining a larger single data set cohort of women with COVID-19 over a longer period than prior studies, to our knowledge.

    Methods

    This cohort study was determined exempt from review and informed consent by the Institutional Review Board of the University of California, Irvine, owing to lack of patient-identifying information. Approval for the use of the data was obtained from Vizient. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

    Using the Vizient Clinical Data Base/Resource Manager (CDB/RM), we compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021. The CDB/RM is an administrative, clinical, and financial database of more than 650 academic centers and their community affiliates. Data represent clinical information submitted by 97% of academic medical centers across the US, representing a broad range of patients across geographic zones. Childbirth was identified based on clinical classification software procedural codes of 134 for cesarean delivery; 135 for forceps, vacuum, or breech delivery; 136 for artificial rupture of membrane to assist delivery; and 137 for other procedures to assist delivery. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)7 diagnosis of U07.1. Women who received a diagnosis of COVID-19 during the same admission in which they underwent childbirth were included. Demographic characteristics, gestational age, and comorbidities were compared between groups. Race and ethnicity were self-reported; these data were examined because research has found that individuals from racial and ethnic minority groups are disproportionally affected by COVID-19 compared with White individuals. The primary outcome was in-hospital mortality. Discharge disposition and in-hospital death were reported in all patients. Secondary outcomes included hospital length of stay (LOS), rates of intensive care unit (ICU) admission and mechanical ventilation, and discharge status.

    Statistical Analysis

    Comparisons were performed using t test for continuous variables and χ2 analysis for categorical variables. Odds ratios (ORs) were calculated to determine the odds of mortality associated with COVID-19 for each gestational age group. Analyses were performed using Stata statistical software version 16 (StataCorp). P values were 2-tailed, and significance was set at P < .05. Data were analyzed from April 1 to April 30, 2021.

    Results

    Among 869 079 women who gave birth at 499 US medical centers, 18 715 women (2.2%) had COVID-19 and 850 364 women (97.8%) did not. Most women in both cohorts were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]), and 8060 women (43.1%) were White in the COVID-19 cohort, compared with 499 501 women (58.7%) who were White in the non–COVID-19 cohort (Table 1). Women with COVID-19, compared with women giving birth without COVID-19, were more likely to be Hispanic (8132 women [43.5%] vs 189 725 women [22.3%]) and/or Black (3792 women [20.3%] vs 153 783 women [18.1%]). The most common comorbidities for women giving birth with COVID-19 included obesity (3956 women [21.1%]), anemia (2310 women [12.3%]), and chronic pulmonary disease (1437 women [7.7%]). There was no significant difference in the number of cesarean deliveries performed (6088 women with COVID-19 [32.5%] vs 273 810 women without COVID-19 [32.2%]; P = .57). The median (range) LOS was 2 (1-211) days for women with COVID-19 and 2 (1-370) days for women without COVID-19 (P < .001).

    Women giving birth with COVID-19, compared with those without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; OR, 5.84 [95% CI, 5.46-6.25]; P  < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P  < .001), and in-hospital mortality (24 women [0.1%] vs 71 women [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001) (Table 2).

    Additionally, women with COVID-19, compared with women without COVID-19, were more likely to have a preterm delivery of less than 37 weeks (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). A total of 779 women with COVID-19 (4.2%) delivered at less than 32 weeks, compared with 22 355 women without COVID-19 (2.6%) (Table 3).

    Discussion

    To our knowledge, this cohort study is the largest single-database study of women giving birth with COVID-19, and we found that women with COVID had an overall peripartum death rate of 0.1%. The death rates and need for ICU admission and respiratory failure requiring intubation were significantly higher among COVID-19 women. Our findings are similar to those by Jering et al,2 who reported a 0.14% (9 of 6380 women) death rate for women giving birth with COVID-19 vs 0.005% (20 of 400 066 women) among women without COVID-19.2 These data also align with the international living meta-analysis by Allotey et al,6 which found increased admission to ICU and increased need for invasive ventilation for pregnant and recently pregnant women with COVID-19 compared with a cohort of nonpregnant women of reproductive age.

    Our study also found that women who had COVID-19 were more likely to be Black or Hispanic compared with women without COVID-19. This information is critically important given the ongoing issues surrounding health care disparities and race. When considering mortality during childbirth, it is important to understand that racial disparities have been well established preceding the COVID-19 pandemic; however, they have likely been augmented by the pandemic.8-10 In fact, previous data from the Centers for Disease Control and Prevention have demonstrated that Black and American Indian or Alaskan Native mothers in the US are 2- to 3-fold more likely to die from pregnancy-related causes. Of note, pregnancy-related mortality rate in the US has been increasing over the last 10 years and is now approximately 0.017%. The mortality rate is approximately 0.044% for Black mothers.9 While the reasons behind this difference are complex, much research has supported the role of health disparities, social and structural determinants of health, discrimination, health care access and quality, and disproportionate burden of underlying comorbidities.11 Each of these factors has been heightened during the COVID-19 pandemic, and therefore further study on the association of COVID-19 with outcomes among mothers from these communities is necessary.

    Our subset analysis based on gestational age found that women with COVID-19 were more likely to deliver at less than 37 weeks than women who did not have COVID-19. Our findings were consistent with a study by Villar et al5 that found higher rates of preterm birth in a multinational cohort study, as well as with Jering and colleagues,2 who reported that COVID-19 was associated with higher odds of preterm birth. This is in contrast to a study by Adhikari and colleagues12 that reported no difference in preterm birth between women with COVID-19 vs those without. Our findings suggest that additional research is warranted to understand the physiological mechanism of COVID-19 in preterm birth.

    Limitations

    There are several limitations to this study, including those inherent to retrospective administrative database studies, including missing data, misclassification, and potential coding inaccuracy. The CDB/RM database is limited to in-hospital mortality and does not contain follow-up data; thus, reported mortality likely underestimates the true mortality. Other limitations include the inability to distinguish patients with COVID-19 who were symptomatic and who were admitted for management of their symptoms versus patients who were asymptomatic and had test results positive for SARS-CoV-2 infection when they were admitted for their birth.

    Conclusions

    This cohort study found that women with COVID-19 who were giving birth had a statistically significantly higher mortality rate of 0.13% compared with women without COVID-19. The need for ICU admission and respiratory failure requiring intubation were statistically significantly higher among women with COVID-19. Future research is needed to further understand the pathophysiology of COVID-19 during pregnancy and to better characterize the long-term sequelae.

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    Article Information

    Accepted for Publication: June 2, 2021.

    Published: August 11, 2021. doi:10.1001/jamanetworkopen.2021.20456

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Chinn J et al. JAMA Network Open.

    Corresponding Author: Ninh T. Nguyen, MD, University of California, Irvine Medical Center, 333 City Bldg W, Ste 1600, Orange, CA 92868 (ninhn@hs.uci.edu).

    Author Contributions: Dr Nguyen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Chinn, Sedighim, Nguyen.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Chinn, Sedighim, Nguyen.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Sedighim, Kirby.

    Administrative, technical, or material support: Chinn, Nguyen.

    Supervision: Sedighim, Hameed, Jolley, Nguyen.

    Conflict of Interest Disclosures: Dr Nguyen reported receiving personal fees from Olympus and Endogastric Solutions outside the submitted work. No other disclosures were reported.

    References
    1.
    Mullins  E, Evans  D, Viner  RM, O’Brien  P, Morris  E.  Coronavirus in pregnancy and delivery: rapid review.   Ultrasound Obstet Gynecol. 2020;55(5):586-592. doi:10.1002/uog.22014PubMedGoogle ScholarCrossref
    2.
    Jering  KS, Claggett  BL, Cunningham  JW,  et al.  Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19.   JAMA Intern Med. 2021;181(5):714-717. doi:10.1001/jamainternmed.2020.9241PubMedGoogle ScholarCrossref
    3.
    Elshafeey  F, Magdi  R, Hindi  N,  et al.  A systematic scoping review of COVID-19 during pregnancy and childbirth.   Int J Gynaecol Obstet. 2020;150(1):47-52. doi:10.1002/ijgo.13182PubMedGoogle ScholarCrossref
    4.
    Di Mascio  D, Khalil  A, Saccone  G,  et al.  Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.   Am J Obstet Gynecol MFM. 2020;2(2):100107. doi:10.1016/j.ajogmf.2020.100107PubMedGoogle Scholar
    5.
    Villar  J, Ariff  S, Gunier  RB,  et al.  Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID multinational cohort study.   JAMA Pediatr. 2021. doi:10.1001/jamapediatrics.2021.1050PubMedGoogle Scholar
    6.
    Allotey  J, Stallings  E, Bonet  M,  et al; for PregCOV-19 Living Systematic Review Consortium.  Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.   BMJ. 2020;370:m3320. doi:10.1136/bmj.m3320PubMedGoogle Scholar
    7.
    World Health Organization.  International Statistical Classification of Diseases, Tenth Revision (ICD-10). World Health Organization; 1992.
    8.
    Nguyen  NT, Chinn  J, Nahmias  J,  et al.  Outcomes and mortality among adults hospitalized with COVID-19 at US Medical Centers.   JAMA Netw Open. 2021;4(3):e210417. doi:10.1001/jamanetworkopen.2021.0417PubMedGoogle Scholar
    9.
    Janevic  T, Glazer  KB, Vieira  L,  et al.  Racial/ethnic disparities in very preterm birth and preterm birth before and during the COVID-19 pandemic.   JAMA Netw Open. 2021;4(3):e211816. doi:10.1001/jamanetworkopen.2021.1816PubMedGoogle Scholar
    10.
    Kuehn  B.  Disparities in maternal mortality.   JAMA. 2019;322(16):1545. doi:10.1001/jama.2019.16156PubMedGoogle Scholar
    11.
    Webb Hooper  M, Nápoles  AM, Pérez-Stable  EJ.  COVID-19 and racial/ethnic disparities.   JAMA. 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598PubMedGoogle ScholarCrossref
    12.
    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.2020.29256PubMedGoogle Scholar
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