A reassuring study by researchers in Denmark indicates that while 5% of pregnant women with coronavirus disease 2019 (COVID-19) may require hospitalization, severe maternal and neonatal outcomes are rare. The research team has released their findings as a preprint on the medRxiv* server.
Earlier studies have shown that pregnancy is a risk factor for poor outcomes following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Such outcomes notably include miscarriage and preterm birth, and neonatal intensive care unit admission, as well as maternal admission to an intensive care unit and Cesarean section.
Risk factors for SARS-CoV-2 infection in pregnancy include older age, obesity, chronic underlying conditions, and ethnicity.
However, such conclusions may be biased, probably because the studies were hospital-based rather than community-based, excluding many milder cases. Another important cause of bias is the choice of historical controls, which means all adverse outcomes in the pandemic cohort that are in excess of the expected number will be attributed to SARS-CoV-2, whether rightly or wrongly.
Finally, community-based testing will potentially impact the prevalence rates, which in turn will affect the estimated incidence of mild or asymptomatic cases vs. severe cases.
Risk factors for severe COVID-19
In the current study, a team of researchers in Denmark mined the National Patient Register and Danish Microbiology Database to carry out their own prospective study from patient medical records.
The incidence of SARS-CoV-2 infection in pregnancy was 5%, among approximately 83,000 pregnancies. They found that compared with non-infected pregnant women, 5.5% of pregnancies complicated by COVID-19 required hospitalization for this reason.
Pregnancies complicated by obesity were at almost three-fold higher risk of severe COVID-19 (defined as requiring hospitalization), while smoking increased the risk approximately fivefold, as did asthma.
Women who were infected after the pregnancy crossed 22 weeks (about five months) had approximately four times the risk in matched controls, up to 27 weeks. Meanwhile, those who caught the infection between 28-32 weeks, that is, in the third trimester, had almost five times the risk compared to controls.
Asthma and non-Danish ethnicity doubled the risk for infection but not the severity of illness.
Most obstetric nor neonatal complications were not increased by the presence of the infection. Maternal and neonatal deaths from infected pregnancies during the study period were zero.
More women chose to terminate their pregnancy in the COVID-19 cohort. Moreover, 1.5% of COVID-19 pregnant women had pneumonia, indicating they had 16-fold higher odds compared to non-infected pregnancies.
What are the implications?
This population-based study on pregnant women with COVID-19 did not reveal any increased risk of pregnancy-related complications, or adverse outcomes in the newborn population, compared to controls.
Whereas testing in Denmark was limited to the severely ill at the beginning of the pandemic, in March 2020, mild cases were included beginning in April 2020, while close contacts were eligible for testing in May of the same year. The same month, all pregnant women in the hospital began to be tested.
This allowed a straightforward adjusted comparison to be made between pregnant women with and without SARS-CoV-2 infection during gestation. While obesity, smoking, infection from the second trimester onwards, and asthma increased the odds of severe COVID-19 in pregnancy, infection odds were higher in those with foreign ethnicity and asthma.
This is the first time smoking has been identified as a high-risk factor for severe COVID-19 in pregnancy. The increased risk of infection in foreign-born women may be due to a mix of cultural and socioeconomic factors.
The only adverse outcome identified was an increased incidence of pneumonia and a higher probability of late termination of pregnancy, irrespective of the severity of infection. The failure to detect differential rates of Cesarean section, induction of labor, or preterm delivery, between the cohorts in this study, contrasts with a large Nordic collaborative study.
The reasons for the higher rate of pregnancy terminations deserve to be explored further to rule out any association with SARS-CoV-2 infection.
The researchers write:
The results indicate that the outcomes of SARS-CoV-2 infection in pregnancy might not be as severe as proposed by previous studies in which more severe cases were included. Testing strategy and how cases are included naturally influence the results and should be considered.”
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.