Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection

José Villar,Adejumoke Idowu Ayede,Laura Salazar,Mustapha Ado Usman,Muhammad Baffah Aminu,Saturday Etuk,Hadiza Galadanci,Shabina Ariff,Stephen Kennedy ,Zulfiqar A Bhutta ,Philippe Deruelle,Alexey Kholin,Robert B Gunier,Ana Langer,Federico Prefumo,Jorge Arturo Cardona–Pérez ,Manuela Oberto,Eduardo Alfredo Duro ,Carmen Vecciarelli,Enrico Ferrazi ,Yetunde O John-Akinola ,Becky Liu,Nerea Maíz ,Ricardo Nieto,Irene Cetin,Mohak Mhatre,Valeria Savasi,Roberto Casale,Perla Karina García-May ,Michael G Gravett,Ramachandran Thiruvengadam,Hellas Cena,Sherief Abd-Elsalam,Paolo Cavoretto ,Vincent Bizor Nachinab,Carola Capelli,Mónica Savorani,Sarah Rae Easter,Loïc Sentilhes,Daniel Orós ,Marynéa Silva Do Vale,Joanna Sichitiu,Constanza P Soto Conti,Babagana Bako,Paola Roggero,Stephen Rauch,Jagjit S Teji ,Ernawati Ernawati,Satoru Ikenoue,Aris T Papageorghiou

doi:10.1001/jamapediatrics.2021.1050

Abstract

Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. 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. COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. 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. 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. 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.

Highlights

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
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, 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)

Summary

Methods

Study Design The Oxford Tropical Research Ethics Committee and all local ethics committees approved the study, which did not interfere with clinical management. The study protocol, including the laboratory tests used, has been previously published.[10]. For 8 months from March 2, 2020, we enrolled women 18 years or older at any stage of pregnancy or delivery with the diagnosis of COVID-19 during the present pregnancy based on laboratory confirmation of COVID-19 and/or radiologic pulmonary findings suggestive of COVID-1911 or 2 or more predefined COVID-19 symptoms. A range of different real-time polymerase chain reaction and antibody tests were used at participating institutions (eBox in the Supplement). Two immediately concomitant pregnant women 18 years or older without any of those diagnostic criteria were enrolled per woman with COVID-19 diagnosis to create an unbiased sample of all pregnant women without COVID-19 diagnosis in these institutions.

Results

Discussion

Conclusion