Abstract
BACKGROUND: Understanding the varied impact of COVID-19 severity on pregnancy outcomes is crucial for informed clinical management and targeted interventions.
OBJECTIVE: To evaluate the impact of COVID-19 on pregnancy outcomes, distinguishing between pregnant women managed in primary care and those requiring hospitalization.
SEARCH STRATEGY: Regulatory authorities actively promoted global cooperation on COVID-19's impact during pregnancy. Data were obtained through these regulatory bodies and direct researcher communication rather than through systematic searches.
SELECTION CRITERIA: Data sources required secondary population-based data to identify pregnancies with COVID-19, along with hospitalization, diagnostic and medication codes. Eligibility for the meta-analysis was determined through protocol evaluation and researcher consultations.
DATA COLLECTION AND ANALYSIS: PRISMA-IPD and Cochrane guidelines for prospective meta-analysis were followed. Protocols and definitions were standardized across sources, and a common R script was developed. Initially, crude and adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated to assess adverse outcomes in pregnant women with and without COVID-19 in each data source. Estimates were stratified by trimester at infection and hospitalization status. Subsequently, data were pooled using a random-effects meta-analysis.
MAIN RESULTS: Data from 10 sources across seven countries contributed to the meta-analysis, including 86 210 pregnant women diagnosed with COVID-19, of whom 4.4% were hospitalized. Non-hospitalized pregnant women with COVID-19 had no increased risks of adverse outcomes compared to pregnant women without COVID-19. However, hospitalized women with COVID-19 in each trimester had higher risks of cesarean section, preterm birth, and LBW compared to pregnant women without COVID-19. Hospitalization due to COVID-19 in the third trimester was associated with increased risk of stillbirth (aRR 5.90, 95% CI: 2.22-15.71, I 2 = 0%). First-trimester hospitalizations due to COVID-19 did not show heightened risks of GDM (aRR 2.08, 95% CI: 0.93-4.64, I 2 = 65%), pre-eclampsia (aRR 1.79, 95% CI: 0.48-6.66, I 2 = 71%), or major congenital anomalies (aRR 1.30, 95% CI: 0.55-3.06, I 2 = 0%).
CONCLUSIONS AND RELEVANCE: COVID-19 requiring hospitalization is associated with adverse pregnancy outcomes, emphasizing the need to prevent severe illness during pregnancy. This study also highlights the importance of international collaboration for gathering pregnancy data and shows that building global research networks is essential for responding to future health crises.
| Original language | English |
|---|---|
| Journal | International Journal of Gynecology and Obstetrics |
| Early online date | 15 Dec 2025 |
| DOIs | |
| Publication status | E-pub ahead of print - 15 Dec 2025 |
Bibliographical note
Publisher Copyright:© 2025 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Funding
The research leading to the results for CONSIGN was conducted as part of the activities of the EU PE&PV Research Network, which is a public academic partnership coordinated by the Utrecht University (UU), The Netherlands. The project has received support from the EMA under the Framework service contract nr EMA/2018/28/PE and was scientifically coordinated by the University Medical Center Utrecht (UMCU). The content of this document expresses the opinion of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties. Electronic healthcare data sources participating in the CONSIGN EHR study were partly funded by the EMA under the above-mentioned Framework service contract. Each of the other participating sites in this meta-analysis has its own funding to collect the data and generate the evidence. The Canadian Mother-Child (CAMCCO) Active Surveillance Initiative is a pan-Canadian program on drug safety and efficacy in pregnancy funded by the Canadian Institutes of Health Research (CIHR), and the Canada Foundation for Innovation (CFI), that is scientifically coordinated by CHU Sainte-Justine in Montreal, Quebec, Canada. The Sentinel System is a U.S. government initiative managed and funded by the U.S. Food and Drug Administration (FDA) and was scientifically coordinated by Harvard Pilgrim Health Care Institute. This project was supported by Task Order 75F40122F19005 and 75F40119F19001 under Master Agreements HHSF223201400030I and 75F40119D10037, from FDA. The FDA approved the study protocol including statistical analysis plan and reviewed and approved this manuscript. Coauthors from the FDA (JH, LS, WH) participated in the results interpretation and in the preparation and decision to submit the manuscript for publication. The FDA had no role in data collection, management, or analysis.
| Funders |
|---|
| Canada Foundation for Innovation |
| European Medicines Agency |
| Canadian Institutes of Health Research |
| Food and Drug Administration |
Keywords
- adverse outcomes
- COVID-19
- hospitalization
- international collaboration
- meta-analysis
- pregnancy
Fingerprint
Dive into the research topics of 'Adverse outcomes among pregnant women with COVID-19 according to hospitalization status: A prospective individual participant data meta-analysis in Europe and North America'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver