SARS-CoV-2 infection in mothers does not have a significant teratogenic effect

In a recent Birth Defects Research study, United States-based scientists determined that infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first trimester of pregnancy does not increase the risk of any specific congenital malformations.

Study: First trimester COVID-19 and the risk of major congenital malformations–International Registry of Coronavirus Exposure in Pregnancy. Image Credit: SciePro / Shutterstock.com

Background

Vertical transmission of viruses from the mothers to the fetus is a major healthcare concern, as it can lead to severe congenital malformations. Birth defects are defined as structural and functional anomalies in infants that occur during pregnancy.

Some viral infections that are notorious for causing congenital malformations during pregnancy include cytomegalovirus, herpes simplex and varicella-zoster virus, Toxoplasmosis gondii, and Zika virus.  

In pregnant women with confirmed coronavirus disease 2019 (COVID-19), transplacental transmission of SARS-CoV-2 is considered a rare event. However, congenital malformations can occur, even in absence of transplacental transmission. In pregnant women with influenza infection, for example, abnormally high body temperature can cause neural tube defects in infants.    

In the current study, scientists evaluate the risk of birth defects in pregnant women who have been exposed to SARS-CoV-2 during the first 12 weeks of pregnancy.

Study design

The International Registry of Coronavirus Exposure in Pregnancy (IRCEP) was utilized to assess the risk of birth defects. The IRCEP is an observational cohort study that has been designed to estimate the risk of perinatal adversities in infants born to women diagnosed with COVID-19.

Adult women who had been tested for or had a confirmed COVID-19 diagnosis during pregnancy enrolled for the IRCEP study between June 2020 and July 2021. Information on SARS-CoV-2 infection, pregnancy outcomes, birth defects, and potential risk factors were collected from the participants through online questionnaires.

The analysis of malformations was restricted to women with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection or clinical diagnosis of COVID-19 during the first trimester of pregnancy.

In the IRCEP study, over 17,000 women participated from 78 countries. SARS-CoV-2 infection was reported by 1,727 women, whereas 10,235 women mentioned negative SARS-CoV-2 test results.

In the current analysis, women who completed the follow-up and provided information regarding the presence of birth defects were included. This led to the identification of 92 women with SARS-CoV-2 infection and 292 women without infection who served as reference pregnancies.

Important observations

The primary analysis included women who enrolled before the end of pregnancy, whereas a second sensitive analysis included women who enrolled before the prenatal screening for malformations. The final expanded analysis included women who enrolled in the study after pregnancy.

The primary analysis revealed that the prevalence of birth defects was 3.3% among SARS-CoV-2-infected women and 2.7% among non-infected women. Similarly, the sensitive analysis found that about 3% and 1.2% of infected and non-infected pregnancies were associated with birth defects, respectively.

According to the expanded analysis, the prevalence of birth defects was 4.4% and 1.8% among infected and non-infected women, respectively.

Among SARS-CoV-2-infected women, three cases of birth defects were identified. However, no specific pattern of birth defects was noticed among these infants. This is reassuring, as fetal exposure to any kind of pathogen is generally associated with a specific pattern of birth defects.

Implications

The study findings indicate that maternal SARS-CoV-2 infection during the first 12 weeks of pregnancy does not increase the risk of birth defects in infants. The current study specifically focuses on infections during the first trimester, as most birth defects develop during this period.

Since the study has been conducted on a small number of pregnant women, the relative risk estimates may not be precise. Thus, more studies with larger sample sizes are required to conclusively understand the impact of SARS-CoV-2 infection on birth defects.

Journal reference:

  • HernĂĄndez-DĂ­az, S., Smith, L. H., Wyszynski, D. F., et al. (2022). First trimester COVID-19 and the risk of major congenital malformations–International Registry of Coronavirus Exposure in Pregnancy. Birth Defects Research. doi:10.1002/bdr2.2070