Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis

Abstract

Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes.

Data sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020.

Study eligibility criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area.

Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis.

Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81).

Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Keywords: COVID-2019; SARS-CoV-2; maternal mortality; neonatal mortality; pneumonia; pregnancy; preterm birth; small-for-gestational-age.

Figure 1

PRISMA diagram for risk factor analysis study The PRISMA flow diagram outlines the identification and recruitment of studies and final inclusion of individual patient data for this study. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Smith. Individual patient data meta-analysis: risk factors among COVID-19 pregnancies. Am J Obstet Gynecol 2023.

Figure 2

Incidence of outcomes by study The incidence and 95% confidence intervals of selected adverse outcomes across the 21 participating studies, including: A, intensive care unit admission, B, ventilation, C, pregnancy-related death, D, preeclampsia, E, cesarean delivery, F, stillbirth, G, neonatal death, H, low birthweight, and I, preterm birth. Studies are grouped by World Bank income group levels: lower-middle–income countries are shown in red; upper-middle–income countries are shown in green; high-income countries are shown in blue. Two studies (shown in purple) are multicountry studies that contain countries from multiple income groups. The complete list of countries for each of these multicountry studies is presented in Table 1. Smith. Individual patient data meta-analysis: risk factors among COVID-19 pregnancies. Am J Obstet Gynecol 2023.