Adverse outcomes among pregnant women with COVID-19 according to hospitalization status: A prospective individual participant data meta-analysis in Europe and North America

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, I2 = 0%). First-trimester hospitalizations due to COVID-19 did not show heightened risks of GDM (aRR 2.08, 95% CI: 0.93-4.64, I2 = 65%), pre-eclampsia (aRR 1.79, 95% CI: 0.48-6.66, I2 = 71%), or major congenital anomalies (aRR 1.30, 95% CI: 0.55-3.06, I2 = 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.