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5. Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis

Author

Smith, Emily R., Oakley, Erin, Grandner, Gargi Wable, Rukundo, Gordon, Farooq, Fouzia, Ferguson, Kacey, Baumann, Sasha, Adams Waldorf, Kristina Maria, Afshar, Yalda, Ahlberg, Mia, Ahmadzia, Homa, Akelo, Victor, Aldrovandi, Grace, Bevilacqua, Elisa, Bracero, Nabal, Brandt, Justin S., Broutet, Natalie, Carrillo, Jorge, Conry, Jeanne, Cosmi, Erich, Crispi, Fatima, Crovetto, Francesca, del Mar Gil, Maria, Delgado-López, Camille, Divakar, Hema, Driscoll, Amanda J., Favre, Guillaume, Fernandez Buhigas, Irene, Flaherman, Valerie, Gale, Christopher, Godwin, Christine L., Gottlieb, Sami, Gratacós, Eduard, He, Siran, Hernandez, Olivia, Jones, Stephanie, Joshi, Sheetal, Kalafat, Erkan, Khagayi, Sammy, Knight, Marian, Kotloff, Karen L., Lanzone, Antonio, Laurita Longo, Valentina, Le Doare, Kirsty, Lees, Christoph, Litman, Ethan, Lokken, Erica M., Madhi, Shabir A., Magee, Laura A., Martinez-Portilla, Raigam Jafet, Metz, Torri D., Miller, Emily S., Money, Deborah, Moungmaithong, Sakita, Mullins, Edward, Nachega, Jean B., Nunes, Marta C., Onyango, Dickens, Panchaud, Alice, Poon, Liona C., Raiten, Daniel, Regan, Lesley, Sahota, Daljit, Sakowicz, Allie, Sanin-Blair, Jose, Stephansson, Olof, Temmerman, Marleen, Thorson, Anna, Thwin, Soe Soe, Tippett Barr, Beth A., Tolosa, Jorge E., Tug, Niyazi, Valencia-Prado, Miguel, Visentin, Silvia, von Dadelszen, Peter, Whitehead, Clare, Wood, Mollie, Yang, Huixia, Zavala, Rebecca, and Tielsch, James M.

Published
2023
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7. Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates

Author

Huebner, Emily M., Gudjónsdóttir, Margrét Johansson, Dacanay, Matthew B., Nguyen, Shayla, Brokaw, Alyssa, Sharma, Kavita, Elfvin, Anders, Hentz, Elisabet, Rivera, Ysabella Raceli, Burd, Nicole, Shivakumar, Megana, Coler, Brahm, Li, Miranda, Li, Amanda, Munson, Jeff, Orvis, Austyn, Coleman, Michelle, Jacobsson, Bo, Rajagopal, Lakshmi, and Adams Waldorf, Kristina M.

Published
2022
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8. Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

Author

Dudley, Dawn M, Van Rompay, Koen K, Coffey, Lark L, Ardeshir, Amir, Keesler, Rebekah I, Bliss-Moreau, Eliza, Grigsby, Peta L, Steinbach, Rosemary J, Hirsch, Alec J, MacAllister, Rhonda P, Pecoraro, Heidi L, Colgin, Lois M, Hodge, Travis, Streblow, Daniel N, Tardif, Suzette, Patterson, Jean L, Tamhankar, Manasi, Seferovic, Maxim, Aagaard, Kjersti M, Martín, Claudia Sánchez-San, Chiu, Charles Y, Panganiban, Antonito T, Veazey, Ronald S, Wang, Xiaolei, Maness, Nicholas J, Gilbert, Margaret H, Bohm, Rudolf P, Adams Waldorf, Kristina M, Gale, Michael, Rajagopal, Lakshmi, Hotchkiss, Charlotte E, Mohr, Emma L, Capuano, Saverio V, Simmons, Heather A, Mejia, Andres, Friedrich, Thomas C, Golos, Thaddeus G, and O'Connor, David H

Subjects
Animals, Primates, Abortion, Spontaneous, Pregnancy, Female, Male, Stillbirth, Kaplan-Meier Estimate, Zika Virus, Zika Virus Infection, Abortion, Spontaneous, Immunology, Medical and Health Sciences
Abstract

Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection.

Published
2018

9. Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain

Author

Adams Waldorf, Kristina M, Nelson, Branden R, Stencel-Baerenwald, Jennifer E, Studholme, Colin, Kapur, Raj P, Armistead, Blair, Walker, Christie L, Merillat, Sean, Vornhagen, Jay, Tisoncik-Go, Jennifer, Baldessari, Audrey, Coleman, Michelle, Dighe, Manjiri K, Shaw, Dennis WW, Roby, Justin A, Santana-Ufret, Veronica, Boldenow, Erica, Li, Junwei, Gao, Xiaohu, Davis, Michael A, Swanstrom, Jesica A, Jensen, Kara, Widman, Douglas G, Baric, Ralph S, Medwid, Joseph T, Hanley, Kathryn A, Ogle, Jason, Gough, G Michael, Lee, Wonsok, English, Chris, Durning, W McIntyre, Thiel, Jeff, Gatenby, Chris, Dewey, Elyse C, Fairgrieve, Marian R, Hodge, Rebecca D, Grant, Richard F, Kuller, LaRene, Dobyns, William B, Hevner, Robert F, Gale, Michael, and Rajagopal, Lakshmi

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Infection, Neurological, Good Health and Well Being, Animals, Disease Models, Animal, Female, Fetus, Humans, Macaca nemestrina, Microcephaly, Neurogenesis, Pregnancy, Pregnancy Complications, Infectious, Zika Virus, Zika Virus Infection, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

Published
2018

10. Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model

Author

Manuel, Gygeria, primary, Coleman, Michelle, additional, Orvis, Austyn S., additional, Munson, Jeff, additional, Li, Amanda, additional, Kapur, Raj P., additional, Li, Miranda, additional, Li, Edmunda, additional, Armistead, Blair, additional, Rajagopal, Lakshmi, additional, and Adams Waldorf, Kristina M., additional

Published
2024
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11. Testing pulmonary physiology in ventilated non‐human primates.

Author

Cervantes, Orlando, Berg, Melissa R., Kapnadak, Siddhartha G., Miller, Elizabeth, Fountain, Connie, Curtis, Britni, Thelen, Sandi, Ruff, Shannon, Huang, Hazel, Altemeier, William, and Adams Waldorf, Kristina M.

Subjects
PHYSIOLOGY, WEIGHT loss, VIRUS diseases, PRIMATES, LUNG diseases, RESPIRATORY diseases, POSITIVE end-expiratory pressure, PLANT protection
Abstract

Background: Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow‐volume and pressure‐volume loops. Application of this protocol during mechanical ventilation in non‐human (NHP) models would represent a major advance in respiratory viral disease research. Methods: We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation. Results: The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%–81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2). There was also a 16%–45% decline in lung compliance. Conclusion: We describe a new approach to performing pulmonary physiology testing protocol in non‐human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Cryopreservation of Human Mucosal Leukocytes.

Author

Hughes, Sean M, Shu, Zhiquan, Levy, Claire N, Ferre, April L, Hartig, Heather, Fang, Cifeng, Lentz, Gretchen, Fialkow, Michael, Kirby, Anna C, Adams Waldorf, Kristina M, Veazey, Ronald S, Germann, Anja, von Briesen, Hagen, McElrath, M Juliana, Dezzutti, Charlene S, Sinclair, Elizabeth, Baker, Chris AR, Shacklett, Barbara L, Gao, Dayong, and Hladik, Florian

Subjects
Vagina, Mucous Membrane, Leukocytes, Humans, Cryopreservation, Female, General Science & Technology
Abstract

BackgroundUnderstanding how leukocytes in the cervicovaginal and colorectal mucosae respond to pathogens, and how medical interventions affect these responses, is important for developing better tools to prevent HIV and other sexually transmitted infections. An effective cryopreservation protocol for these cells following their isolation will make studying them more feasible.Methods and findingsTo find an optimal cryopreservation protocol for mucosal mononuclear leukocytes, we compared cryopreservation media and procedures using human vaginal leukocytes and confirmed our results with endocervical and colorectal leukocytes. Specifically, we measured the recovery of viable vaginal T cells and macrophages after cryopreservation with different cryopreservation media and handling procedures. We found several cryopreservation media that led to recoveries above 75%. Limiting the number and volume of washes increased the fraction of cells recovered by 10-15%, possibly due to the small cell numbers in mucosal samples. We confirmed that our cryopreservation protocol also works well for both endocervical and colorectal leukocytes. Cryopreserved leukocytes had slightly increased cytokine responses to antigenic stimulation relative to the same cells tested fresh. Additionally, we tested whether it is better to cryopreserve endocervical cells on the cytobrush or in suspension.ConclusionsLeukocytes from cervicovaginal and colorectal tissues can be cryopreserved with good recovery of functional, viable cells using several different cryopreservation media. The number and volume of washes has an experimentally meaningful effect on the percentage of cells recovered. We provide a detailed, step-by-step protocol with best practices for cryopreservation of mucosal leukocytes.

Published
2016

14. GBS hyaluronidase mediates immune suppression in a TLR2/4- and IL-10-dependent manner during pregnancy-associated infection

Author

Coleman, Michelle, primary, Orvis, Austyn, additional, Brokaw, Alyssa, additional, Furuta, Anna, additional, Sharma, Kavita, additional, Quach, Phoenicia, additional, Bhullar, Avneet, additional, Sanghavi, Rhea, additional, Nguyen, Shayla, additional, Sweeney, Erin, additional, Seepersaud, Ravin, additional, Armistead, Blair, additional, Adams Waldorf, Kristina M., additional, and Rajagopal, Lakshmi, additional

Published
2023
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20. COVID-19 Vaccine Hesitancy among English-Speaking Pregnant Women Living in Rural Western United States

Author

Cox, Elizabeth, primary, Sanchez, Magali, additional, Baxter, Carly, additional, Crary, Isabelle, additional, Every, Emma, additional, Munson, Jeff, additional, Stapley, Simone, additional, Stonehill, Alex, additional, Taylor, Katherine, additional, Widmann, Willamina, additional, Karasz, Hilary, additional, and Adams Waldorf, Kristina, additional

Published
2023
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21. Author Correction: Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Author

Beaudry-Richard, Alexandra, Nadeau-Vallée, Mathieu, Prairie, Élizabeth, Maurice, Noémie, Heckel, Émilie, Nezhady, Mohammad, Pundir, Sheetal, Madaan, Ankush, Boudreault, Amarilys, Hou, Xin, Quiniou, Christiane, Sierra, Estefania Marin, Beaulac, Alexandre, Lodygensky, Gregory, Robertson, Sarah A., Keelan, Jeffrey, Adams Waldorf, Kristina M., Olson, David M., Rivera, Jose-Carlos, Lubell, William D., Joyal, Jean-Sebastien, Bouchard, Jean-François, and Chemtob, Sylvain

Published
2020
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23. Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis

Author

Smith, Emily R, primary, Oakley, Erin, additional, Grandner, Gargi Wable, additional, Ferguson, Kacey, additional, Farooq, Fouzia, additional, Afshar, Yalda, additional, Ahlberg, Mia, additional, Ahmadzia, Homa, additional, Akelo, Victor, additional, Aldrovandi, Grace, additional, Tippett Barr, Beth A, additional, Bevilacqua, Elisa, additional, Brandt, Justin S, additional, Broutet, Nathalie, additional, Fernández Buhigas, Irene, additional, Carrillo, Jorge, additional, Clifton, Rebecca, additional, Conry, Jeanne, additional, Cosmi, Erich, additional, Crispi, Fatima, additional, Crovetto, Francesca, additional, Delgado-López, Camille, additional, Divakar, Hema, additional, Driscoll, Amanda J, additional, Favre, Guillaume, additional, Flaherman, Valerie J, additional, Gale, Chris, additional, Gil, Maria M, additional, Gottlieb, Sami L, additional, Gratacós, Eduard, additional, Hernandez, Olivia, additional, Jones, Stephanie, additional, Kalafat, Erkan, additional, Khagayi, Sammy, additional, Knight, Marian, additional, Kotloff, Karen, additional, Lanzone, Antonio, additional, Le Doare, Kirsty, additional, Lees, Christoph, additional, Litman, Ethan, additional, Lokken, Erica M, additional, Laurita Longo, Valentina, additional, Madhi, Shabir A, additional, Magee, Laura A, additional, Martinez-Portilla, Raigam Jafet, additional, McClure, Elizabeth M, additional, Metz, Tori D, additional, Miller, Emily S, additional, Money, Deborah, additional, Moungmaithong, Sakita, additional, Mullins, Edward, additional, Nachega, Jean B, additional, Nunes, Marta C, additional, Onyango, Dickens, additional, Panchaud, Alice, additional, Poon, Liona C, additional, Raiten, Daniel, additional, Regan, Lesley, additional, Rukundo, Gordon, additional, Sahota, Daljit, additional, Sakowicz, Allie, additional, Sanin-Blair, Jose, additional, Söderling, Jonas, additional, Stephansson, Olof, additional, Temmerman, Marleen, additional, Thorson, Anna, additional, Tolosa, Jorge E, additional, Townson, Julia, additional, Valencia-Prado, Miguel, additional, Visentin, Silvia, additional, von Dadelszen, Peter, additional, Adams Waldorf, Kristina, additional, Whitehead, Clare, additional, Yassa, Murat, additional, and Tielsch, Jim M, additional

Published
2023
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24. Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis

Author

Smith, Emily R, Oakley, Erin, Grandner, Gargi Wable, Ferguson, Kacey, Farooq, Fouzia, Afshar, Yalda, Ahlberg, Mia, Ahmadzia, Homa, Akelo, Victor, Aldrovandi, Grace, Tippett Barr, Beth A, Bevilacqua, Elisa, Brandt, Justin S, Broutet, Nathalie, Fernández Buhigas, Irene, Carrillo, Jorge, Clifton, Rebecca, Conry, Jeanne, Cosmi, Erich, Crispi, Fatima, Crovetto, Francesca, Delgado-López, Camille, Divakar, Hema, Driscoll, Amanda J, Favre, Guillaume, Flaherman, Valerie J, Gale, Chris, Gil, Maria M, Gottlieb, Sami L, Gratacós, Eduard, Hernandez, Olivia, Jones, Stephanie, Kalafat, Erkan, Khagayi, Sammy, Knight, Marian, Kotloff, Karen, Lanzone, Antonio, Le Doare, Kirsty, Lees, Christoph, Litman, Ethan, Lokken, Erica M, Laurita Longo, Valentina, Madhi, Shabir A, Magee, Laura A, Martinez-Portilla, Raigam Jafet, McClure, Elizabeth M, Metz, Tori D, Miller, Emily S, Money, Deborah, Moungmaithong, Sakita, Mullins, Edward, Nachega, Jean B, Nunes, Marta C, Onyango, Dickens, Panchaud, Alice, Poon, Liona C, Raiten, Daniel, Regan, Lesley, Rukundo, Gordon, Sahota, Daljit, Sakowicz, Allie, Sanin-Blair, Jose, Söderling, Jonas, Stephansson, Olof, Temmerman, Marleen, Thorson, Anna, Tolosa, Jorge E, Townson, Julia, Valencia-Prado, Miguel, Visentin, Silvia, von Dadelszen, Peter, Adams Waldorf, Kristina, Whitehead, Clare, Yassa, Murat, Tielsch, Jim M, and Perinatal COVID PMA Study Collaborators

Subjects
Epidemiology, Clinical Trials and Supportive Activities, Reproductive health and childbirth, Low Birth Weight and Health of the Newborn, Vaccine Related, Pregnancy, Preterm, Clinical Research, Biodefense, Infant Mortality, Humans, Prospective Studies, Lung, Pediatric, SARS-CoV-2, Prevention, Infant, COVID-19, Pneumonia, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, Pneumonia & Influenza, Female, Pregnant Women, Maternal health, Infection, Perinatal COVID PMA Study Collaborators
Abstract

IntroductionDespite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Published
2023

26. Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate

Author

Adams Waldorf, Kristina M, Stencel-Baerenwald, Jennifer E, Kapur, Raj P, Studholme, Colin, Boldenow, Erica, Vornhagen, Jay, Baldessari, Audrey, Dighe, Manjiri K, Thiel, Jeff, Merillat, Sean, Armistead, Blair, Tisoncik-Go, Jennifer, Green, Richard R, Davis, Michael A, Dewey, Elyse C, Fairgrieve, Marian R, Gatenby, J Christopher, Richards, Todd, Garden, Gwenn A, Diamond, Michael S, Juul, Sandra E, Grant, Richard F, Kuller, LaRene, Shaw, Dennis W W, Ogle, Jason, Gough, G Michael, Lee, Wonsok, English, Chris, Hevner, Robert F, Dobyns, William B, Gale, Michael, Jr, and Rajagopal, Lakshmi

Subjects
Zika virus infection -- Complications and side effects, Brain diseases -- Development and progression, Biological sciences, Health
Abstract

Author(s): Kristina M Adams Waldorf (corresponding author) [1]; Jennifer E Stencel-Baerenwald [2, 3]; Raj P Kapur [4, 5]; Colin Studholme [6, 7, 8]; Erica Boldenow [6, 9]; Jay Vornhagen [9, [...]

Published
2016
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30. Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Author

Beaudry-Richard, Alexandra, Nadeau-Vallée, Mathieu, Prairie, Élizabeth, Maurice, Noémie, Heckel, Émilie, Nezhady, Mohammad, Pundir, Sheetal, Madaan, Ankush, Boudreault, Amarilys, Hou, Xin, Quiniou, Christiane, Sierra, Estefania Marin, Beaulac, Alexandre, Lodygensky, Gregory, Robertson, Sarah A., Keelan, Jeffrey, Adams Waldorf, Kristina M., Olson, David M., Rivera, Jose-Carlos, Lubell, William D., Joyal, Jean-Sebastien, Bouchard, Jean-François, and Chemtob, Sylvain

Published
2018
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31. Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods

Author

Smith, Emily R., primary, Oakley, Erin, additional, He, Siran, additional, Zavala, Rebecca, additional, Ferguson, Kacey, additional, Miller, Lior, additional, Grandner, Gargi Wable, additional, Abejirinde, Ibukun-Oluwa Omolade, additional, Afshar, Yalda, additional, Ahmadzia, Homa, additional, Aldrovandi, Grace, additional, Akelo, Victor, additional, Tippett Barr, Beth A., additional, Bevilacqua, Elisa, additional, Brandt, Justin S., additional, Broutet, Natalie, additional, Fernández Buhigas, Irene, additional, Carrillo, Jorge, additional, Clifton, Rebecca, additional, Conry, Jeanne, additional, Cosmi, Erich, additional, Delgado-López, Camille, additional, Divakar, Hema, additional, Driscoll, Amanda J., additional, Favre, Guillaume, additional, Flaherman, Valerie, additional, Gale, Christopher, additional, Gil, Maria M., additional, Godwin, Christine, additional, Gottlieb, Sami, additional, Hernandez Bellolio, Olivia, additional, Kara, Edna, additional, Khagayi, Sammy, additional, Kim, Caron Rahn, additional, Knight, Marian, additional, Kotloff, Karen, additional, Lanzone, Antonio, additional, Le Doare, Kirsty, additional, Lees, Christoph, additional, Litman, Ethan, additional, Lokken, Erica M., additional, Laurita Longo, Valentina, additional, Magee, Laura A., additional, Martinez-Portilla, Raigam Jafet, additional, McClure, Elizabeth, additional, Metz, Torri D., additional, Money, Deborah, additional, Mullins, Edward, additional, Nachega, Jean B., additional, Panchaud, Alice, additional, Playle, Rebecca, additional, Poon, Liona C., additional, Raiten, Daniel, additional, Regan, Lesley, additional, Rukundo, Gordon, additional, Sanin-Blair, Jose, additional, Temmerman, Marleen, additional, Thorson, Anna, additional, Thwin, Soe, additional, Tolosa, Jorge E., additional, Townson, Julia, additional, Valencia-Prado, Miguel, additional, Visentin, Silvia, additional, von Dadelszen, Peter, additional, Adams Waldorf, Kristina, additional, Whitehead, Clare, additional, Yang, Huixia, additional, Thorlund, Kristian, additional, and Tielsch, James M., additional

Published
2022
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35. Impact of progesterone on innate immunity and cell death after influenza A virus H1N1 2009 infection of lung and placental cells in vitro

Author

Li, Miranda, Li, Amanda, Huang, Hazel, Munson, Jeff, Obadan, Adebimpe, Fuller, Deborah H., and Adams Waldorf, Kristina M.

Subjects
General Medicine, Article
Abstract

The influenza A virus (IAV) 2009 H1N1 pandemic was associated with an increased risk of maternal mortality, preterm birth, and stillbirth. The underlying mechanism for severe maternal lung disease and stillbirth is incompletely understood, but IAV infection is known to activate innate immunity triggering the release of cytokines. Elucidating the impact of progesterone (P4), a key hormone elevated in pregnancy, on the innate immune and inflammatory response to IAV infection is a critical step in understanding the pathogenesis of adverse maternal-fetal outcomes. IAV H1N1 pdm/09 was used to infect cell lines Calu-3 (lung adenoma) and ACH-3P (extravillous trophoblast) with or without P4 (100 nM) at multiplicity of infections (MOI) 0, 0.5, and 3. Cells were harvested at 24 and 48 hours post infection (hpi) and analyzed for cytopathic effects (CPE), replicating virus (TCID50), cytotoxicity (Lactate Dehydrogenase (LDH) assay), and NLRP3 inflammasome activation (caspase-1 activity, fluorometric assay). Activation of antiviral innate immunity was quantified (RT-qPCR, Luminex) by measuring biomarker gene and protein expression of innate immune activation (IFIT1, IFNB), inflammation (IL6), interferon signaling (MXA), chemokines (IL-8, IL-10). Both Calu-3 and ACH-3P were highly permissible to IAV infection at each timepoint as demonstrated by CPE and recovery of replicating virus. In Calu-3, progesterone treatment was associated with a significant increase in cytotoxicity, increased gene expression of IL6, and increased protein expression of IFN-β, IL-6, and IL-18. Conversely, in ACH-3P, progesterone treatment was associated with significantly suppressed cytotoxicity, decreased gene expression of IFNB, IL6 and IL1B, and increased protein expression of IFN-β and IL-6. In both cell lines, caspase-1 activity was significantly decreased after progesterone treatment, indicating NLRP3 inflammasome activation was not underlying the higher cell death in Calu-3. In summary, these data provide evidence that progesterone plays a dual role by ameliorating viral infection in the placenta but exacerbating influenza A virus-associated injury in the lung through nongenomic modulation of the innate immune response.

Published
2022

36. Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates

Author

Adams Waldorf, Kristina M., Singh, Natasha, Mohan, Aarthi R., Young, Roger C., Ngo, Lisa, Das, Ananya, Tsai, Jesse, Bansal, Aasthaa, Paolella, Louis, Herbert, Bronwen R., Sooranna, Suren R., Gough, Michael G., Astley, Cliff, Vogel, Keith, Baldessari, Audrey E., Bammler, Theodor K., MacDonald, James, Gravett, Michael G., Rajagopal, Lakshmi, and Johnson, Mark R.

Published
2015
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42. Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth

Author

Li, Miranda, primary, Brokaw, Alyssa, additional, Furuta, Anna M., additional, Coler, Brahm, additional, Obregon-Perko, Veronica, additional, Chahroudi, Ann, additional, Wang, Hsuan-Yuan, additional, Permar, Sallie R., additional, Hotchkiss, Charlotte E., additional, Golos, Thaddeus G., additional, Rajagopal, Lakshmi, additional, and Adams Waldorf, Kristina M., additional

Published
2021
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43. Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients

Author

Lokken, Erica M., primary, Taylor, G. Gray, additional, Huebner, Emily M., additional, Vanderhoeven, Jeroen, additional, Hendrickson, Sarah, additional, Coler, Brahm, additional, Sheng, Jessica S., additional, Walker, Christie L., additional, McCartney, Stephen A., additional, Kretzer, Nicole M., additional, Resnick, Rebecca, additional, Kachikis, Alisa, additional, Barnhart, Nena, additional, Schulte, Vera, additional, Bergam, Brittany, additional, Ma, Kimberly K., additional, Albright, Catherine, additional, Larios, Valerie, additional, Kelley, Lori, additional, Larios, Victoria, additional, Emhoff, Sharilyn, additional, Rah, Jasmine, additional, Retzlaff, Kristin, additional, Thomas, Chad, additional, Paek, Bettina W., additional, Hsu, Rita J., additional, Erickson, Anne, additional, Chang, Andrew, additional, Mitchell, Timothy, additional, Hwang, Joseph K., additional, Gourley, Rebecca, additional, Erickson, Stephen, additional, Delaney, Shani, additional, Kline, Carolyn R., additional, Archabald, Karen, additional, Blain, Michela, additional, LaCourse, Sylvia M., additional, and Adams Waldorf, Kristina M., additional

Published
2021
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44. Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State

Author

Lokken, Erica M., primary, Huebner, Emily M., additional, Taylor, G. Gray, additional, Hendrickson, Sarah, additional, Vanderhoeven, Jeroen, additional, Kachikis, Alisa, additional, Coler, Brahm, additional, Walker, Christie L., additional, Sheng, Jessica S., additional, al-Haddad, Benjamin J.S., additional, McCartney, Stephen A., additional, Kretzer, Nicole M., additional, Resnick, Rebecca, additional, Barnhart, Nena, additional, Schulte, Vera, additional, Bergam, Brittany, additional, Ma, Kimberly K., additional, Albright, Catherine, additional, Larios, Valerie, additional, Kelley, Lori, additional, Larios, Victoria, additional, Emhoff, Sharilyn, additional, Rah, Jasmine, additional, Retzlaff, Kristin, additional, Thomas, Chad, additional, Paek, Bettina W., additional, Hsu, Rita J., additional, Erickson, Anne, additional, Chang, Andrew, additional, Mitchell, Timothy, additional, Hwang, Joseph K., additional, Erickson, Stephen, additional, Delaney, Shani, additional, Archabald, Karen, additional, Kline, Carolyn R., additional, LaCourse, Sylvia M., additional, and Adams Waldorf, Kristina M., additional

Published
2021
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45. Amniotic fluid interleukin 6 and interleukin 8 are superior predictors of fetal lung injury compared with maternal or fetal plasma cytokines or placental histopathology in a nonhuman primate model

Author

McCartney, Stephen A., primary, Kapur, Raj, additional, Liggitt, H. Denny, additional, Baldessari, Audrey, additional, Coleman, Michelle, additional, Orvis, Austyn, additional, Ogle, Jason, additional, Katz, Ronit, additional, Rajagopal, Lakshmi, additional, and Adams Waldorf, Kristina M., additional

Published
2021
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47. Higher SARS-CoV-2 Infection Rate in Pregnant Patients

Author

LOKKEN, Erica M., TAYLOR, G. Gray, HUEBNER, Emily M., VANDERHOEVEN, Jeroen, HENDRICKSON, Sarah, COLER, Brahm, SHENG, Jessica S., WALKER, Christie L., MCCARTNEY, Stephen A., KRETZER, Nicole M., RESNICK, Rebecca, KACHIKIS, Alisa, BARNHART, Nena, SCHULTE, Vera, BERGAM, Brittany, K, Kimberly, ALBRIGHT, Catherine, LARIOS, Valerie, KELLEY, Lori, LARIOS, Victoria, EMHOFF, Sharilyn, RAH, Jasmine, RETZLAFF, Kristin, THOMAS, Chad, PAEK, Bettina W., HSU, Rita J., ERICKSON, Anne, CHANG, Andrew, MITCHELL, Timothy, HWANG, Joseph K., GOURLEY, Rebecca, ERICKSON, Stephen, DELANEY, Shani, KLINE, Carolyn R., ARCHABALD, Karen, BLAIN, Michela, LACOURSE, Sylvia M., and ADAMS WALDORF, Kristina M.

Subjects
Alaskan Native, Adult, Washington, Washington State, SARS-CoV-2, Original Research: Obstetrics, Racial Groups, coronavirus, Hispanic, COVID-19, Severity of Illness Index, Cohort Studies, fetus, Pacific Islander, Young Adult, ethnic disparity, Black, Pregnancy, American Indian, Humans, Female, Pregnancy Complications, Infectious, Retrospective Studies
Abstract

During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood.This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State.Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State.A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%).The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Published
2021

48. Landscape of Preterm Birth Therapeutics and a Path Forward

Author

Coler, Brahm Seymour, primary, Shynlova, Oksana, additional, Boros-Rausch, Adam, additional, Lye, Stephen, additional, McCartney, Stephen, additional, Leimert, Kelycia B., additional, Xu, Wendy, additional, Chemtob, Sylvain, additional, Olson, David, additional, Li, Miranda, additional, Huebner, Emily, additional, Curtin, Anna, additional, Kachikis, Alisa, additional, Savitsky, Leah, additional, Paul, Jonathan W., additional, Smith, Roger, additional, and Adams Waldorf, Kristina M., additional

Published
2021
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49. Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates

Author

Coleman, Michelle, primary, Armistead, Blair, additional, Orvis, Austyn, additional, Quach, Phoenicia, additional, Brokaw, Alyssa, additional, Gendrin, Claire, additional, Sharma, Kavita, additional, Ogle, Jason, additional, Merillat, Sean, additional, Dacanay, Matthew, additional, Wu, Tsung-Yen, additional, Munson, Jeff, additional, Baldessari, Audrey, additional, Vornhagen, Jay, additional, Furuta, Anna, additional, Nguyen, Shayla, additional, Adams Waldorf, Kristina M., additional, and Rajagopal, Lakshmi, additional

Published
2021
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50. Clinical Characteristics of 46 Pregnant Women with a SARS-CoV-2 Infection in Washington State

Author

Lokken, Erica M., Walker, Christie L., Delaney, Shani, Kachikis, Alisa, Kretzer, Nicole M., Erickson, Anne, Resnick, Rebecca, Vanderhoeven, Jeroen, Hwang, Joseph K., Barnhart, Nena, Rah, Jasmine, Mccartney, Stephen A., Ma, Kimberly K., Huebner, Emily M., Thomas, Chad, Sheng, Jessica S., Paek, Bettina W., Retzlaff, Kristin, Kline, Carolyn R., Munson, Jeff, Blain, Michela, Lacourse, Sylvia M., Deutsch, Gail, and Adams Waldorf, Kristina

Subjects
obesity, SARS-CoV-2, coronavirus, preterm birth, asthma, Article, infection, maternal morbidity, respiratory insufficiency, overweight, stillbirth, pregnancy, fetal death, Covid-19
Abstract

Background The impact of the coronavirus disease 2019 (Covid-19) on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease. Objective To describe maternal disease and obstetrical outcomes associated with Covid-19 disease in pregnancy to rapidly inform clinical care. Study Design Retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection from six hospital systems in Washington State between January 21, 2020 and April 17, 2020. Demographics, medical and obstetric history, and Covid-19 encounter data were abstracted from medical records. Results A total of 46 pregnant patients with a SARS-CoV-2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a SARS-CoV-2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5%, n=20 and 50.0%, n=23, respectively). Symptoms resolved in a median of 24 days (interquartile range 13-37). Seven women were hospitalized (16%) including one admitted to the intensive care unit. Six cases (15%) were categorized as severe Covid-19 disease with nearly all patients being either overweight or obese prior to pregnancy, asthma or other co-morbidities. Eight deliveries occurred during the study period, including a preterm birth at 33 weeks to improve pulmonary status in a woman with Class III obesity. One stillbirth occurred of unknown etiology. Conclusions Nearly 15% of pregnant patients developed severe Covid-19, which occurred primarily in overweight or obese women with underlying conditions. Obesity and Covid-19 may synergistically increase risk for a medically-indicated preterm birth to improve maternal pulmonary status in late pregnancy. Collectively, these findings support categorizing pregnant patients as a higher risk group, particularly for those with chronic co-morbidities.

Published
2020

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