COVID-19 infection associated with fetal demise

According to a recent study published in the American Journal of Obstetrics & Gynecology, COVID-19 infection is associated with fetal demise.

COVID-19 has caused over 4,300,000 deaths across 552,000,000 confirmed cases since December 2019, with poor maternal outcomes associated with COVID-19 infection during pregnancy. However, a clear association between COVID-19 infection and adverse fetal outcomes has not been made.

An indication has been made of an association between COVID-19 infection and loss of pregnancy, with researchers hypothesizing COVID-19 in the fetal tissues is responsible for pregnancy loss through fetal infection. A transmission of COVID-19 to live neonates has been determined, making it a vertically transmissible virus according to the WHO.

Investigators conducted a systematic review to address the knowledge gap of stillbirth and miscarriages in women with COVID-19 infection. Studies evaluating stillbirth or late miscarriage among pregnant individuals with COVID-19 infection during pregnancy published from December 1, 2019, to April 30, 2022, were included.

COVID-19 infection was determined by positive real-time reverse transcription-polymerase chain reaction or placental COVID-19 infection. Studies which were meta-analysis, conference abstracts, of women not fulfilling eligibility criteria, or had other possible stillbirth or late miscarriage causes were excluded.

The Pubmed and Web of Sciences databased were searched using the search terms, “fetal demise,” “miscarriage,” “stillbirth,” “COVID-19,” and “SARS-CoV-2.” Using the Meta-analysis Of Observational Studies in Epidemiology guidelines, 2 researchers independently assessed abstracts and full texts, with a third consulted to resolve discrepancies.

Data extraction was completed by 2 independent investigators. Data collected included country, date, article type, maternal characteristics, number of fetuses, and obstetrical complications. COVID-19 data was also collected, including infection features, vaccination status, hospitalization for COVID-19, and disease severity.

Fetal and placental data collected included fetal sex and growth, time between COVID-19 infection and stillbirth or late miscarriage, and fetal and placental COVID-19 positives. COVID-19 infection and severity were classified using WHO criteria.

There were 54 articles in the final analysis, with 184 mothers and 190 fetuses across all studies. Of the fetuses, 166 were stillbirths and 24 late miscarriages. An intermediate to good methodological quality was found across studies, determined using the Mayo Clinic Evidence-Based Practice Center tool.

Of mothers, 42 were multiparous. Common comorbidities included diabetes mellitus, obesity, and chorioamnionitis. COVID-19 was treated using steroids in 6 women, remdesivir in 3, tocilizumab in 2, and anakinra in 1.

Gestational age ranged from 14 to 39.2 weeks at the time of COVID-19 infection. Severe COVID-19 was seen in under 5% of women, with most women having mild-to-moderate COVID-19. Only 10.3% of cases had a confirmed viral strain, and no participants had received a COVID-19 vaccination at the time of analysis.

Stillbirths and late miscarriages were commonly observed 6 to 13 days after confirmed COVID-19 infection or symptom onset. The second trimester of pregnancy was the most common period of stillbirths and late miscarriages. A positive test of COVID-19 in at least 1 tissue was found in 12.1% of fetuses, and 69.5% placentas were positive for COVID-19.

Most placentas, “presented the histologic features previously observed in transplacentally transmitted infections,” according to investigators. A confirmed in utero COVID-19 infection transmission was seen in 5.8% of fetuses, while a possible in utero COVID-19 infection transmission was seen in 60%.

These results indicated transplacental COVID-19 may be associated with fetal demise. Investigators recommended further research to determine if stillbirth occurs mostly in the late second or early third trimester of pregnancy.

Reference

Alcover N, Regiroli G, Benachi A, Vauloup-Fellous C, Vivanti AJ, De Luca D. Systematic review and synthesis of stillbirths and late miscarriages following SARS-CoV-2 infections. American Journal of Obstetrics & Gynecology. 2023;229(2). doi:10.1016/j.ajog.2023.01.019