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Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study
Open accessAbstract
BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.
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“In terms of maternal CMDs, it was found that COVID-19 and pre-eclampsia impact perinatal outcomes (such as preterm birth, severe perinatal morbidity and mortality) in an additive fashion264.”
From A global view of hypertensive disorders and diabetes mellitus during pregnancy (2022) · cites this paper as [264]
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Metadata
- Authors
- Papageorghiou, A. T., Deruelle, P., Gunier, R. B., Rauch, S., García-May, P. K., Mhatre, M., Usman, M. A., Abd-Elsalam, S., Etuk, S., Simmons, L. E., Napolitano, R., Deantoni, S., Liu, B., Prefumo, F., Savasi, V., do Vale, M. S., Baafi, E., Zainab, G., Nieto, R., Maiz, N., Aminu, M. B., Cardona-Perez, J. A., Craik, R., Winsey, A., Tavchioska, G., Bako, B., Oros, D., Rego, A., Benski, A. C., Hassan-Hanga, F., Savorani, M., Giuliani, F., Sentilhes, L., Risso, M., Takahashi, K., Vecchiarelli, C., Ikenoue, S., Thiruvengadam, R., Soto Conti, C. P., Ferrazzi, E., Cetin, I., Nachinab, V. B., Ernawati, E., Duro, E. A., Kholin, A., Firlit, M. L., Easter, S. R., Sichitiu, J., Bowale, A., Casale, R., Cerbo, R. M., Cavoretto, P. I., Eskenazi, B., Thornton, J. G., Bhutta, Z. A., Kennedy, S. H., & Villar, J.
- Affiliations
- St George's Hospital (GB)
- Hôpitaux Universitaires de Strasbourg (FR)
- University of California, Berkeley (US)
- Institute for Social Security and Services for State Workers (MX)
- Tufts Medical Center (US)
- Muhammad Abdullahi Wase Teaching Hospital (NG)
- Tanta University (EG)
- University Of Calabar Teaching Hospital (NG)
- University of Washington (US)
- University College London Hospitals NHS Foundation Trust (GB)
- John Radcliffe Hospital (GB)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- University of Milan (IT)
- Aga Khan University (PK)
- Abubakar Tafawa Balewa University (NG)
- Gombe State University (NG)
- Hospital Clínico Universitario Lozano Blesa (ES)
- Universidade Federal de Minas Gerais (BR)
- University Hospital of Geneva (CH)
- Aminu Kano Teaching Hospital (NG)
- Universidad de Morón (AR)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Hospital Universitario Austral (AR)
- Jikei University School of Medicine (JP)
- Sanatorio Otamendi y Miroli (AR)
- Keio University (JP)
- Translational Health Science and Technology Institute (IN)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Universitas Airlangga (ID)
- Universidad de Buenos Aires (AR)
- University of Illinois Hospital & Health Sciences System (US)
- Harvard University (US)
- Hôpital Necker-Enfants Malades (FR)
- Hospital Posadas (AR)
- Policlinico San Matteo Fondazione (IT)
- IRCCS Ospedale San Raffaele (IT)
- University of Nottingham (GB)
- Corresponding author
- Papageorghiou, Aris T.
- ORCID
- Papageorghiou, Aris T.
- Deruelle, Philippe
- Gunier, Robert B.
- Rauch, Stephen
- García-May, Perla K.
- Usman, Mustapha Ado
- Abd-Elsalam, Sherief
- Napolitano, Raffaele
- Deantoni, Sonia
- Liu, Becky
- Prefumo, Federico
- Savasi, Valeria
- Aminu, Muhammad Baffah
- Craik, Rachel
- Winsey, Adele
- Bako, Babagana
- Oros, Daniel
- Benski, Anne Caroline
- Hassan-Hanga, Fatimah
- Giuliani, Francesca
- Takahashi, Ken
- Vecchiarelli, Carmen
- Ikenoue, Satoru
- Thiruvengadam, Ramachandran
- Ferrazzi, Enrico
- Cetin, Irene
- Ernawati, Ernawati
- Duro, Eduardo A.
- Firlit, Michelle L.
- Easter, Sarah Rae
- Sichitiu, Joanna
- Cerbo, Rosa Maria
- Cavoretto, Paolo Ivo
- Eskenazi, Brenda
- Thornton, Jim G.
- Bhutta, Zulfiqar A.
- Kennedy, Stephen H.
- Villar, José
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 225
- Issue
- 3
- Pages
- 289.e1-289.e17
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC8233533
- OpenAlex
- W3174033175
- Cited by
- 311
- References
- 34
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 45 · 2023: 78 · 2022: 108 · 2021: 34
- FWCI
- 60.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universitas Airlangga Repository (Universitas Airlangga) (acceptedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Zaguan (University of Zaragoza Repository) (submittedVersion, cc-by)
- Greater South Information System
- Funders
- University of Oxford (0009083)
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Obstetrics and Gynecology › COVID-19 Impact on Reproduction
- Health Sciences › Medicine › Clinical Neurology › Neurological Complications and Syndromes
- Keywords
- preeclampsia, COVID-19 in pregnancy, SARS-CoV-2, maternal morbidity, neonatal morbidity, preterm birth, nulliparous women, risk factors, pregnancy outcomes, maternal mortality, neonatal mortality, SARS-CoV-2 seroprevalence, SARS-CoV-2 viral load, SARS-CoV-2 variants
- MeSH terms
- COVID-19, SARS-CoV-2, Adult, Female, Humans, Longitudinal Studies, Pre-Eclampsia, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Prospective Studies, Risk Factors, Hypertension, Pregnancy-Induced, Premature Birth
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