TY - JOUR
T1 - Maternal and Neonatal Morbidity and Mortality among Pregnant Women with and without COVID-19 Infection
T2 - The INTERCOVID Multinational Cohort Study
AU - Villar, José
AU - Ariff, Shabina
AU - Gunier, Robert B.
AU - Thiruvengadam, Ramachandran
AU - Rauch, Stephen
AU - Kholin, Alexey
AU - Roggero, Paola
AU - Prefumo, Federico
AU - Do Vale, Marynéa Silva
AU - Cardona-Perez, Jorge Arturo
AU - Maiz, Nerea
AU - Cetin, Irene
AU - Savasi, Valeria
AU - Deruelle, Philippe
AU - Easter, Sarah Rae
AU - Sichitiu, Joanna
AU - Soto Conti, Constanza P.
AU - Ernawati, Ernawati
AU - Mhatre, Mohak
AU - Teji, Jagjit Singh
AU - Liu, Becky
AU - Capelli, Carola
AU - Oberto, Manuela
AU - Salazar, Laura
AU - Gravett, Michael G.
AU - Cavoretto, Paolo Ivo
AU - Nachinab, Vincent Bizor
AU - Galadanci, Hadiza
AU - Oros, Daniel
AU - Ayede, Adejumoke Idowu
AU - Sentilhes, Loïc
AU - Bako, Babagana
AU - Savorani, Mónica
AU - Cena, Hellas
AU - García-May, Perla K.
AU - Etuk, Saturday
AU - Casale, Roberto
AU - Abd-Elsalam, Sherief
AU - Ikenoue, Satoru
AU - Aminu, Muhammad Baffah
AU - Vecciarelli, Carmen
AU - Duro, Eduardo A.
AU - Usman, Mustapha Ado
AU - John-Akinola, Yetunde
AU - Nieto, Ricardo
AU - Ferrazi, Enrico
AU - Bhutta, Zulfiqar A.
AU - Langer, Ana
AU - Kennedy, Stephen H.
AU - Papageorghiou, Aris T.
N1 - Funding Information:
Funding/Support: The study was supported by the COVID-19 Research Response Fund from the University of Oxford (reference 0009083). Dr Papageorghiou is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the National Institute for Health Research Biomedical Research Centre Biomedical Research Centre funding scheme.
Funding Information:
Additional Contributions: We are grateful to the following colleagues for their contributions to the study: Josephine Agyeman-Duah, MSc (Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK), study coordinator, Nkawkaw, Ghana; Eric Baafi, MD (Holy Family Hospital, Nkawkaw, Ghana), data collection, Ghana; Anne Caroline Benski, MD (Hôpitaux Universitaires de Genève, Département de la Femme, de l’Enfant et de l'Adolescent, Geneva, Switzerland), data collection, Geneva, Switzerland; Rachel Craik, BSc (Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK), study coordinator (overall study); Sonia Deantoni, MD (Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK; Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK; Neonatal Care Unit, Department of Public Health and Pediatrics, School of Medicine, University of Turin, Italy), data collection, Oxford, UK, and data input (multiple sites); Ken Takahashi, PhD (Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan), data collection, Jikei, Japan; Gabriela Tavchioska, MSc (Department of Pediatrics, General Hospital Borka Taleski, Prilep, Republic of North Macedonia), data collection, Prilep, Republic of North Macedonia; Jim G. Thornton, MD (Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham, UK), literature reviews and study advisor; Albertina Rego, PhD (Departamento de Pediatria, Faculdade Universidade Federal de Minas Gerais, Belo Horizonte, Brazil), study coordinator, Brazil; and Adele Winsey, PhD (Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK), study coordinator (overall study). Dr Winsey and Ms Craik were supported by the COVID-19 Research Response Fund from the University of Oxford. Other contributors did not receive any compensation (eAppendix 1 in the Supplement). We also thank all the contributing institutions and local researchers involved in the study. eAppendix 2 in the Supplement contains their details as well as details of the study committees.
Funding Information:
reported grants from Oxford University during the conduct of the study. Dr Sentilhes reported personal, lecture, and consulting fees from Ferring Pharmaceutical and personal and lecture fees from Bayer outside the submitted work. Dr Papageorghiou reported grants from National Institute for Health Research Biomedical Research Centre and other support from Intelligent Ultrasound as director outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 Villar J et al. JAMA Pediatrics.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85105199416&partnerID=8YFLogxK
U2 - 10.1001/jamapediatrics.2021.1050
DO - 10.1001/jamapediatrics.2021.1050
M3 - Article
C2 - 33885740
AN - SCOPUS:85105199416
SN - 2168-6203
VL - 175
SP - 817
EP - 826
JO - JAMA Pediatrics
JF - JAMA Pediatrics
IS - 8
ER -
