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Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom. Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom. Department of Paediatrics and Child Health, The Aga Khan University Hospital, Karachi, Pakistan. School of Public Health, University of California, Berkeley, Berkeley. Translational Health Science and Technology Institute, Faridabad, India. National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Department of Woman, Child and Neonate, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Universidade Federal do Maranhão, São Luís, Brazil. Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico. Obstetrics Department, Hospital Universitari Vall d'Hebron, Barcelona Hospital Campus, Barcelona, Spain. Ospedale Vittore Buzzi Children's Hospital, Department of BioMedical and Clinical Sciences, University of Milan, Milan, Italy. Ospedale Luigi Sacco University Hospital, Department of BioMedical and Clinical Sciences, University of Milan, Milan, Italy. Department of Obstetrics and Gynecology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Division of Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Hôpital Universitaire Necker-Enfants Malades, AP-HP, Université de Paris, Paris, France. Division Neonatología, Hospital Materno Infantil Ramón Sarda, Buenos Aires Argentina. Department of Obstetrics and Gynecology, Medical Faculty, Universitas Airlangga, Surabaya, Indonesia. Soetomo General Academic Hospital, Surabaya, Indonesia. Tufts Medical Center, Boston, Massachusetts. Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, Illinois. St George's University Hospitals NHS Foundation Trust, London, United Kingdom. Servicio de Neonatologia del Departamento Materno Infantil del Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina. S.C. Obstetrics 2U, Sant'Anna Hospital, AOU Città della Salute e della scienza di Torino, Turin, Italy. Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, United Kingdom. Department of Obstetrics and Gynecology, University of Washington, Seattle. Department of Global Health, University of Washington, Seattle. Obstetrics and Gynaecology Department, IRCCS San Raffaele Hospital and University, Milan, Italy. Fr. Thomas Alan Rooney Memorial Hospital, Asankragwa, Ghana. Africa Center of Excellence for Population Health and Policy, Bayero University Kano, Kano, Nigeria. Aminu Kano Teaching Hospital, Kano, Nigeria. Aragon Institute of Health Research, Obstetrics Department, Hospital Clínico Universitario Lozano Blesa Zaragoza, Zaragoza, Spain. College of Medicine, University of Ibadan, Ibadan, Nigeria. University College Hospital, Ibadan, Nigeria. Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France. Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medical Sciences, Gombe State University, Gombe, Nigeria. Hospital de Moron, Moron, Provincia de Buenos Aires, Argentina. Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy. Clinical Nutrition and Dietetics Service, Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, University of Pavia, Pavia, Italy. Hospital Regional Lic. Adolfo López Mateos ISSSTE, Mexico City, Mexico. University of Calabar Teaching Hospital, Calabar, Nigeria. Maternal and Child Department, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina. Tropical Medicine and Infectious Diseases Department, Tanta University, Tanta, Egypt. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. Department of Obstetrics and Gynaecology, Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Sanatorio Otamendi, Ciudad de Buenos Aires, Argentina. Universidad de Buenos Aires, Buenos Aires, Argentina. Universidad de Moron, Moron, Argentina. Department of Obstetrics and Gynaecology, Muhammad Abdullahi Wase Teaching Hospital, Kano State, Nigeria. Center for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada. Women and Health Initiative, Global Health and Population Department, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

JAMA pediatrics. 2021;(8):817-826
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Abstract

IMPORTANCE Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. OBJECTIVE To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. DESIGN, SETTING, AND PARTICIPANTS In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. EXPOSURES COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. MAIN OUTCOMES AND MEASURES The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. RESULTS A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. CONCLUSIONS AND RELEVANCE In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Methodological quality

Publication Type : Comparative Study ; Multicenter Study

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