Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.
Villar, Jose MD 1,2; Ariff, Shabina MD 3; Gunier, Robert B. PhD 4; Thiruvengadam, Ramachandran MD 5; Rauch, Stephen MPH 4; Kholin, Alexey MD 6; Roggero, Paola PhD 7,8; Prefumo, Federico PhD 9,10; do Vale, Marynea Silva MD 11; Cardona-Perez, Jorge Arturo MD 12; Maiz, Nerea PhD 13; Cetin, Irene MD 14; Savasi, Valeria PhD 15; Deruelle, Philippe PhD 16; Easter, Sarah Rae MD 17,18; Sichitiu, Joanna MD 19; Soto Conti, Constanza P. MD 20; Ernawati, Ernawati PhD 21,22; Mhatre, Mohak MD 23; Teji, Jagjit Singh MD 24; Liu, Becky MBBS 25; Capelli, Carola MD 26; Oberto, Manuela MD 27; Salazar, Laura MD 28; Gravett, Michael G. MD 29,30; Cavoretto, Paolo Ivo PhD 31; Nachinab, Vincent Bizor MD 32; Galadanci, Hadiza MSc 33,34; Oros, Daniel PhD 35; Ayede, Adejumoke Idowu MD 36,37; Sentilhes, Loic PhD 38; Bako, Babagana MD 39; Savorani, Monica MD 40; Cena, Hellas PhD 41,42; Garcia-May, Perla K. MD 43; Etuk, Saturday MD 44; Casale, Roberto MD 45; Abd-Elsalam, Sherief PhD 46; Ikenoue, Satoru PhD 47; Aminu, Muhammad Baffah MD 48; Vecciarelli, Carmen MD 49; Duro, Eduardo A. MD 50,51; Usman, Mustapha Ado MBBS 52; John-Akinola, Yetunde PhD 36,37; Nieto, Ricardo MD 20; Ferrazi, Enrico MD 8; Bhutta, Zulfiqar A. PhD 53; Langer, Ana MD 54; Kennedy, Stephen H. MD 1,2; Papageorghiou, Aris T. MD 1,2,25
[Article]
JAMA Pediatrics.
175(8):817-826, August 2021.
(Format: HTML, PDF)
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.
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