. 2023 Sep;229(3):288.e1-288.e13.

doi: 10.1016/j.ajog.2023.02.022. Epub 2023 Feb 28.

Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age

Collaborators, Affiliations

Collaborators

of the National COVID Cohort Collaborative Consortium:
Adam B Wilcox, Adam M Lee, Alexis Graves, Alfred Jerrod Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E Williams, Andrew Southerland, Andrew T Girvin, Anita Walden, Anjali A Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J W Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L Rutter, Julie A McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M Walters, Ken Wilkins, Kenneth R Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B Palchuk, Melissa A Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A Francis, Penny Wung Burgoon, Peter Robinson, Philip R O Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A Moffitt, Richard L Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T Miller, Saiju Pyarajan, Sam G Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T O'Neil, Soko Setoguchi, Stephanie S Hong, Steve Johnson, Tellen D Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang

Affiliations

¹ Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC.
² Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC. Electronic address: cliang@mailbox.sc.edu.
³ Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC.
⁴ Department of Obstetrics and Gynecology, School of Medicine Columbia, University of South Carolina, Columbia, SC.
⁵ Department of Integrated Information Technology, College of Engineering and Computing, University of South Carolina, Columbia, SC.
⁶ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁷ Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC.

PMID: 36858096
PMCID: PMC9970919
DOI: 10.1016/j.ajog.2023.02.022

Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age

Tianchu Lyu et al. Am J Obstet Gynecol. 2023 Sep.

. 2023 Sep;229(3):288.e1-288.e13.

doi: 10.1016/j.ajog.2023.02.022. Epub 2023 Feb 28.

Collaborators

of the National COVID Cohort Collaborative Consortium:
Adam B Wilcox, Adam M Lee, Alexis Graves, Alfred Jerrod Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E Williams, Andrew Southerland, Andrew T Girvin, Anita Walden, Anjali A Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J W Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L Rutter, Julie A McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M Walters, Ken Wilkins, Kenneth R Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B Palchuk, Melissa A Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A Francis, Penny Wung Burgoon, Peter Robinson, Philip R O Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A Moffitt, Richard L Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T Miller, Saiju Pyarajan, Sam G Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T O'Neil, Soko Setoguchi, Stephanie S Hong, Steve Johnson, Tellen D Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang

Affiliations

¹ Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC.
² Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC. Electronic address: cliang@mailbox.sc.edu.
³ Department of Epidemiology & Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC.
⁴ Department of Obstetrics and Gynecology, School of Medicine Columbia, University of South Carolina, Columbia, SC.
⁵ Department of Integrated Information Technology, College of Engineering and Computing, University of South Carolina, Columbia, SC.
⁶ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁷ Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC.

PMID: 36858096
PMCID: PMC9970919
DOI: 10.1016/j.ajog.2023.02.022

Abstract

Background: Despite previous research findings on higher risks of stillbirth among pregnant individuals with SARS-CoV-2 infection, it is unclear whether the gestational timing of viral infection modulates this risk.

Objective: This study aimed to examine the association between timing of SARS-CoV-2 infection during pregnancy and risk of stillbirth.

Study design: This retrospective cohort study used multilevel logistic regression analyses of nationwide electronic health records in the United States. Data were from 75 healthcare systems and institutes across 50 states. A total of 191,403 pregnancies of 190,738 individuals of reproductive age (15-49 years) who had childbirth between March 1, 2020 and May 31, 2021 were identified and included. The main outcome was stillbirth at ≥20 weeks of gestation. Exposures were the timing of SARS-CoV-2 infection: early pregnancy (<20 weeks), midpregnancy (21-27 weeks), the third trimester (28-43 weeks), any time before delivery, and never infected (reference).

Results: We identified 2342 (1.3%) pregnancies with COVID-19 in early pregnancy, 2075 (1.2%) in midpregnancy, and 12,697 (6.9%) in the third trimester. After adjusting for maternal and clinical characteristics, increased odds of stillbirth were observed among pregnant individuals with SARS-CoV-2 infection only in early pregnancy (odds ratio, 1.75, 95% confidence interval, 1.25-2.46) and midpregnancy (odds ratio, 2.09; 95% confidence interval, 1.49-2.93), as opposed to pregnant individuals who were never infected. Older age, Black race, hypertension, acute respiratory distress syndrome or acute respiratory failure, and placental abruption were found to be consistently associated with stillbirth across different trimesters.

Conclusion: Increased risk of stillbirth was associated with COVID-19 only when pregnant individuals were infected during early and midpregnancy, and not at any time before the delivery or during the third trimester, suggesting the potential vulnerability of the fetus to SARS-CoV-2 infection in early pregnancy. Our findings underscore the importance of proactive COVID-19 prevention and timely medical intervention for individuals infected with SARS-CoV-2 during early and midpregnancy.

Keywords: COVID-19; electronic health records; gynecology; obstetrics; pregnancy; stillbirth.

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Figures

**Figure 1**
Flowchart of cohort development *EHR*, electronic health record; *N3C*, National COVID Cohort Collaborative. *Lyu. Stillbirth and different maternal SARS-CoV-2 infection time. Am J Obstet Gynecol 2023.*

**Figure 2**
The ORs for stillbirth among pregnant women with COVID-19 in early and midpregnancy *ARDS*, acute respiratory distress syndrome; *COPD*, chronic obstructive pulmonary disease; *NHOPI*, Native Hawaiian and Other Pacific Islander; OR, odds ratio. *Lyu. Stillbirth and different maternal SARS-CoV-2 infection time. Am J Obstet Gynecol 2023.*

**Figure 3**
ORs for stillbirth among pregnant women with COVID-19 (crude model) *ARDS*, acute respiratory distress syndrome; *COPD*, chronic obstructive pulmonary disease; *DOD*, date of delivery; *NHOPI*, Native Hawaiian and Other Pacific Islander; OR, odds ratio. *Lyu. Stillbirth and different maternal SARS-CoV-2 infection time. Am J Obstet Gynecol 2023.*

See this image and copyright information in PMC

References

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Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age

Collaborators

Affiliations

Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age

Authors

Collaborators

Affiliations

Abstract

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical