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

Our take —

This cohort study, which enrolled 2,130 pregnant people across 18 countries from March to October 2020, found an increased risk of maternal and infant morbidity and mortality among 706 participants diagnosed with COVID-19 compared with similar uninfected controls. Despite the potential for residual confounding and lack of generalizability to pregnant people prior to their third trimester, this study supports the inference that COVID-19 may increase the risk of adverse pregnancy outcomes.

Study design

Prospective Cohort

Study population and setting

This cohort study enrolled 2,130 pregnant people (1 case of laboratory or clinically-diagnosed COVID-19 to 2 sequential uninfected controls from the same clinic) across 18 countries on five continents from March to October 2020. If sequential controls were not available at enrollment, or participants were recruited at a hospital admission for delivery, sequential deliveries among pregnant people without COVID-19 were included as controls. The authors assessed the impact of a COVID-19 diagnosis on maternal and neonatal morbidity and mortality, adjusted for country, month entering study, age, history of medical comorbidities, and, in models that included preterm birth as an outcome, previous preterm birth. Primary outcomes included the maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI), all of which are binary composite outcomes of a variety of maternal and neonatal comorbidities and mortality. The risk of each outcome was evaluated using Poisson models with robust standard errors. Sensitivity analyses adjusted for additional potential confounders (marital status, overweight, smoking, and drug use during pregnancy status), restrictions to pregnant participants with laboratory-confirmed COVID-19, and only singleton pregnancies.

Summary of Main Findings

Of the 706 participants with a COVID-19 diagnosis, 656 (92.9%) had laboratory or radiologic confirmation, 288 (40.8%) were asymptomatic, and 214 (30.3%) had three or more symptoms. The most common symptoms were cough (34.1%), fever (28.2%) and loss of smell (17%). Infected and uninfected participants had similar mean age, mean BMI, years of education, prevalence of work outside the home, and prevalence of cohabiting or being married. Participants with COVID-19 were more likely to use recreational drugs (2.8% versus 1.4%), have a previous stillbirth or neonatal death (5.5% versus 3.3%), have diabetes (4.7% versus 1.4%), and be overweight (BMI > 25 kg/m2; 48.6% versus 40.2%). Participants without diagnosed COVID-19 were more likely to smoke (3.8% versus 2.9%) and have a previous pregnancy (70.9% versus 66.8%). Participants with diagnosed COVID-19 were at a higher risk of MMMI (adjusted risk ratio [aRR] 1.54, 95% CI: 1.33, 1.78), SNMI (aRR 2.66, 95% CI 1.69, 4.18), and SPMMI (aRR 2.14, 95% CI: 1.66, 2.75). These results were similar after sensitivity analysis.

Study Strengths

This study included a large number of women from all over the world, which increases generalizability. They also assessed maternal and infant outcomes in a prospective manner after COVID-19 diagnosis, which limits the influence of recall bias.

Limitations

The authors did not specify the pregnancy trimester for each participant, although they did note that most were in their third trimester, which limits the generalizability of their findings to pregnant individuals diagnosed with COVID-19 earlier in pregnancy. They also did not adjust for a variety of other potential confounders including, but not limited to, trimester or level where participants were enrolled (clinic versus hospital). Although they did adjust for country, there may be a great deal of variability in outcomes depending on the particular location where participants were recruited. Those decisions may lead to residual confounding that could bias their findings in unpredictable ways and, if outcomes were correlated at each recruitment site, artificially narrow confidence intervals. Finally, the authors did not address how they handled missing covariate or outcome data.

Value added

This study provides more robust evidence to support that SARS-CoV-2 infection during pregnancy leads to poor maternal and infant outcomes in a geographically diverse group of women.

This review was posted on: 28 May 2021