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

Emily R. Smith, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Erin Oakley, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Gargi Wable Grandner, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Gordon Rukundo, PeriCovid (PREPARE) - Uganda Team, Makerere University - Johns Hopkins University Research Collaboration, Uganda.
Fouzia Farooq, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Kacey Ferguson, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Sasha Baumann, Department of Global Health, George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Kristina Adams Waldorf, Department of Obstetrics and Gynecology, School of Medicine, University of Washington, USA; Department of Global Health, University of Washington, Washington, USA.
Yalda Afshar, Division of Maternal Fetal Medicine, University of California Los Angeles, Los Angeles, CA, United States.
Mia Ahlberg, Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Homa Ahmadzia, Division of Maternal-Fetal Medicine, The George Washington University School of Medicine and Health Sciences.
Victor Akelo, US Centers for Disease Control and Prevention, Kisumu, Kenya.
Grace Aldrovandi, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA.
Elisa Bevilacqua, Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
Nabal Bracero, University of Puerto Rico School of Medicine, Department of Obstetrics and Gynecology; Puerto Rico Obstetrics and Gynecology (PROGyn).
Justin S. Brandt, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Natalie Broutet, Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
Jorge Carrillo, Departmento de Obstetricia y Ginecologia, Clinica Alemana de Santiago, Facultad de Medicina Clinica Alemana-Universidad del Desarrollo, Santiago, Chile.
Jeanne Conry, OBGYN, The International Federation of Gynecology and Obstetrics, London, United Kingdom.
Erich Cosmi, Department of Woman's and Child's Health, Obstetrics and Gynecologic Clinic, University of Padua, Padua, Italy.
Fatima Crispi, BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Universitat de Barcelona, and Center for Biomedical Research on Rare Diseases, CIBER-ER, Barcelona, Spain.
Francesca Crovetto, BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Universitat de Barcelona, and Center for Biomedical Research on Rare Diseases, CIBER-ER, Barcelona, Spain.
Maria Del Gil, Department of Obstetrics and Gynecology, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain; School of Medicine, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain.
Camille Delgado-López, Surveillance for Emerging Threats to Mothers and Babies, Puerto Rico Department of Health, San Juan, Puerto Rico.
Hema Divakar, Asian Research and Training Institute for Skill Transfer (ARTIST), Bengaluru, India.
Amanda J. Driscoll, Center for Vaccine Development and Global Health, University of Maryland, School of Medicine, Baltimore, MD, USA.
Guillaume Favre, Materno-fetal and Obstetrics Research Unit, Department "Femme-Mère-Enfant", University Hospital, Lausanne, Switzerland.
Irene Fernandez Buhigas, Department of Obstetrics and Gynecology, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain; School of Medicine, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain.
Valerie Flaherman, Department of Pediatrics, University of California San Francisco, CA, San Francisco, USA.
Christopher Gale, Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, United Kingdom.
Christine L. Godwin, Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
Sami Gottlieb, Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

Document Type

Journal Article

Publication Date

8-23-2022

Journal

American journal of obstetrics and gynecology

DOI

10.1016/j.ajog.2022.08.038

Keywords

Coronavirus Disease 2019; Maternal Mortality; Neonatal Mortality; Pneumonia; Pregnancy; Preterm Birth; SARS-CoV-2; Small-for-gestational Age

Abstract

OBJECTIVE: This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sPMA via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. STUDY APPRAISAL AND SYNTHESIS METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a two-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (pre-existing diabetes, hypertension, cardiovascular disease) versus those without were at higher risk for COVID-19 severity and pregnancy health outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% CI: 1.12, 2.71) more likely to be admitted to the ICU. Pregnant women who were underweight before pregnancy were at higher risk of ICU admission (RR 5.53, 95% CI: 2.27, 13.44), ventilation (RR 9.36, 95% CI: 3.87, 22.63), and pregnancy-related death (RR 14.10, 95% CI: 2.83, 70.36). Pre-pregnancy obesity was also a risk factor for severe COVID-19 outcomes including ICU admission (RR 1.81, 95% CI: 1.26,2.60), ventilation (RR 2.05, 95% CI: 1.20,3.51), any critical care (RR 1.89, 95% CI: 1.28,2.77), and pneumonia (RR 1.66, 95% CI: 1.18,2.33). Anemic pregnant women with COVID-19 also had increased risk of ICU admission (RR 1.63, 95% CI: 1.25, 2.11) and death (RR 2.36, 95% CI: 1.15, 4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly-known risk factors, including HIV infection, pre-pregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Department

Global Health

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