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Comparative Study
. 2021 Aug 1;175(8):817-826.
doi: 10.1001/jamapediatrics.2021.1050.

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

José Villar  1   2 , Shabina Ariff  3 , Robert B Gunier  4 , Ramachandran Thiruvengadam  5 , Stephen Rauch  4 , Alexey Kholin  6 , Paola Roggero  7   8 , Federico Prefumo  9   10 , Marynéa Silva do Vale  11 , Jorge Arturo Cardona-Perez  12 , Nerea Maiz  13 , Irene Cetin  14 , Valeria Savasi  15 , Philippe Deruelle  16 , Sarah Rae Easter  17   18 , Joanna Sichitiu  19 , Constanza P Soto Conti  20 , Ernawati Ernawati  21   22 , Mohak Mhatre  23 , Jagjit Singh Teji  24 , Becky Liu  25 , Carola Capelli  26 , Manuela Oberto  27 , Laura Salazar  28 , Michael G Gravett  29   30 , Paolo Ivo Cavoretto  31 , Vincent Bizor Nachinab  32 , Hadiza Galadanci  33   34 , Daniel Oros  35 , Adejumoke Idowu Ayede  36   37 , Loïc Sentilhes  38 , Babagana Bako  39 , Mónica Savorani  40 , Hellas Cena  41   42 , Perla K García-May  43 , Saturday Etuk  44 , Roberto Casale  45 , Sherief Abd-Elsalam  46 , Satoru Ikenoue  47 , Muhammad Baffah Aminu  48 , Carmen Vecciarelli  49 , Eduardo A Duro  50   51 , Mustapha Ado Usman  52 , Yetunde John-Akinola  36   37 , Ricardo Nieto  20 , Enrico Ferrazi  8 , Zulfiqar A Bhutta  53 , Ana Langer  54 , Stephen H Kennedy  1   2 , Aris T Papageorghiou  1   2   25
Affiliations
Comparative Study

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

José Villar et al. JAMA Pediatr. .

Erratum in

  • Misspelled Author Name in the Byline.
    [No authors listed] [No authors listed] JAMA Pediatr. 2022 Jan 1;176(1):104. doi: 10.1001/jamapediatrics.2021.4953. JAMA Pediatr. 2022. PMID: 34779828 Free PMC article. No abstract available.

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gunier 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.

Figures

Figure.
Figure.. Gestational Age at Delivery Among Women With COVID-19 Diagnosis, With and Without Symptoms, and Women Without COVID-19 Diagnosis
There were 1420 women without COVID-19 diagnosis (dark blue). In the group of women with COVID-19 diagnosis, 417 women were symptomatic (light blue) and 288 women were asymptomatic (orange). There was a significant trend (P < .001) in shorter gestational age at delivery going from women without COVID-19 diagnosis, to asymptomatic women with COVID-19 diagnosis, to symptomatic women with COVID-19 diagnosis (log-rank test for trend of survivor curves). Five women with missing data were excluded from the figure.
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