July 14, 2020

expert reaction to a case study which finds evidence for the potential transmission of SARS-CoV-2 via the placenta from a mother to her baby

A case study, published in Nature Communications, looked at evidence for the potential transmission of SARS-CoV-2 via the placenta from a mother to her baby.

Dr Ela Chakkarapani, Senior Lecturer Neonatal Neuroscience, University of Bristol, said:

“This case study is indeed an important addition to the existing literature. Data to date has been suggesting in utero transmission may be occurring and this study adds data to further support that. 

“The largest population based study from UK (UKOSS) has shown that out of 12 infants who tested positive following birth to women with confirmed COVID-19, 6 infants tested positive within 12 hours of life. This suggests there is possible in utero transmission. Additionally, antibodies to SARS-CoV-2 had been reported in babies born to mothers with positive SARS-CoV-2 infection which also suggests in utero transmission.

“The case report by Kirstman et al, indicates probable in utero transmission and reported SARS-CoV-2 in placental tissue. SARS-CoV-2 is now reported in maternal blood, placenta, amniotic fluid, neonatal blood and nasopharyngeal samples in this study which suggests the placenta was the route of transmission.

“We have been concerned about the potential neurodevelopmental impact of early life exposure to SARS-CoV-2 in newborn babies. Other viruses like cytomegalovirus and Zika virus have had neurodevelopmental impact on newborn babies and a minority of adults with SARS-CoV-2 infection have been reported to have neurological involvement. This case illustrates the potential impact on the brain. This is concerning for neonatal clinicians. The neuroimaging changes seen in this case study are by no means devastating, but could potentially lead to long term intellectual deficits. It is often challenging to pick up subtle abnormal clinical neurological signs in newborn babies. ​​Given this case report, we need to establish whether babies who have been exposed to SARS-coV-2 have long-term neurodevelopmental impairments. Assessing these babies’ development at 18-24 months in the first instance will help us to understand whether there is an impact of early life SARS-CoV-2 exposure on neurodevelopment. If there is an impact then we could inform the guidance for pregnant women.” 

Prof Alexander Heazell, Professor of Obstetrics  and Director of the Tommy’s Research Centre, Manchester Academic Health Science Centre, The University of Manchester, said:

“This case study does not provide strong evidence for transmission of SARS-CoV-2 via the placenta.

“The study claims that presence of SARS-CoV-2 in the placental tissue is evidence for transmission across the placenta, as seen in the immunohistochemistry in Figure 5. However this figure only shows presence of the virus within the outer layer of the placenta (the syncytiotrophoblast), there is no evidence of the virus in the next layer of cells (the stromal cells). Therefore there is evidence that the placenta itself may be infected, but no evidence that the virus has successfully passed through the placenta to infect the fetus. The placenta often acts as barrier to infection in this way and few types of virus can successfully pass through it.

“The case study also finds immune cells within the area around the placenta (the intervillous space), but this is from the mother’s blood and so again provides no evidence of transplacental transmission. To date there have been no convincing cases of transplacental transmission, so pregnant women should not be alarmed by this report.

“To know if transmission of SARS-CoV-2 to a fetus via the placenta truly occurs then we need high quality studies with large sample sizes and this requires collaboration of research groups.”

Prof Rohan Lewis, Professor of Placental and Integrative Physiology, University of Southampton, said:

“The paper by Vivanti et al. clearly suggests that COVID-19 virus may infect the fetus via the placenta. The presence of COVID-19 proteins and RNA in the placenta alongside detection of viral RNA in samples taken from the baby within one hour of birth makes a convincing case for placenta transmission. It should be noted that the placenta could become infected without transmission to other fetal tissues. The immunological evidence for COVID-19 in the placenta is most evident in the Syncytiotrophoblast, which is the fetus first line of defence within the placenta.

“While this study demonstrates possible placental transfer of COVID-19, this transfer appears to be relatively rare. A previous study of 38 women with COVID-19 suggested there was no placental transmission observed (DOI: 10.5858/arpa.2020-0901-SA).

“In this case, there was chronic intervillous inflammation in the placenta, which could be attributed to COVID-19 and systemic maternal inflammation. Alternatively, chronic inflammation of the villi may have been a pre-existing condition which allowed placental transmission in this case. If some form of pre-existing placental pathology facilitates the transfer of infection, this could explain why COVID-19 infection of the child was observed in this case but not in others. 

“The study also observed neurological signs in the baby consistent with changes seen in adults which highlight the potential risks to the baby infected in the womb or in early life.

“This study highlights the importance of the placenta in defending the fetus from external threats. Research is required to explain why some maternal infections may cross the placenta while others do not and identify who may be at risk. While pregnant women and those around them should take precautions to avoid becoming infected the risk of transmission to the baby in the womb is likely to be low.”

Prof Raheela Khan, Professor of Cellular Physiology, Faculty of Medicine & Health Sciences, University of Nottingham & Trustee of The Physiological Society, said:

“The findings from this study are significant in demonstrating possible materno-fetal transmission of SARs Covid-19 in late pregnancy specifically through the placenta. Evidence from placental histology and neonatal brain MRI is consistent with signs of disease resulting from inflammation. Strength of the study is that several different types of fluids and tissues from both mother and baby tested positive for SARs-CoV-2. The study is a case report based on a single pregnancy so more data is needed to support the observations. It is difficult to be certain about duration of exposure to the virus and the consequent placental infection. The findings may sound concerning however the majority of babies born to mothers with SARS-CoV-2 do not test positive and those who do, such as in this case study, do not tend to become severely ill. Further work is needed to investigate the short and long-term impact of Covid-19 and clinical management of pregnancy now there is evidence that neonatal infection via placental transmission may on occasions play a role.

Prof Christoph Lees, Professor of Obstetrics, Imperial College London & International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Trustee & Chair of the ISUOG Safety Committee, said:

Is this a good quality study?

“This is a very detailed and well characterised case report showing very likely transplacental transmission of the SARS-CoV-2 virus. The authors have gone to great lengths to be as methodologically scrupulous as possible

Are there any limitations or caveats to be aware of?

“The unusual feature of this case is that baby developed some form of transient neurological condition, not unlike what has been described in children and adults. We cannot be sure that the baby’s apparently reversible brain MRI imaging findings were due to the virus itself  as the viral cultures taken from baby’s spinal fluid were negative. If the baby had an infection affecting the brain, we would expect them to have been positive. Reassuringly baby’s ultrasound and brain function tests were normal.

Is this the first known potential case of transplacental transmission?

“This is the most convincing case yet reported of transplacental transmission.

Could something else be going on here?

“It is unusual in a viral infection for baby’s fetal heart rate trace to become abnormal, as it did, so we cannot exclude a co-incidental obstetric problem with baby or placenta that was nothing to do with the virus and might have led to the neurological findings a few days later.

How dangerous is infection with SARS-CoV-2 for new-born babies/pregnant women?

“We now have data from several thousand of pregnancies where mothers had the virus. In some cases the babies are likely to have caught the infection either transplacentally, in the process of labour/delivery or afterwards. There isn’t any evidence that the virus is dangerous for babies, though we cannot exclude the possibility that it can cause fetal or neonatal infection that can be associated with really rare conditions as have been reported in children and adults with COVID-19. To put it another way, the great majority of women who test positive for SARS-CoV-2 or indeed have COVID-19 have normal pregnancy outcomes with healthy babies.

What do we know about neurological symptoms associated with infection by the virus in babies?

“We know very little about this, which is why this case report is potentially important as it may suggest what would be a very rare association with a neurological syndrome in newborn babies that caught the infection whilst in the womb.”

Prof Andrew Shennan, Professor of Obstetrics, King’s College London, said:

“This report suggests that transmission of Covid19 infection may occur between mother and baby before delivery. In this case the baby became sick, but made a full recovery. It remains rare for babies to become infected; in 244 live born babies of infected mothers in the UK, 95% had no sign of the virus, and outcomes are similar to non-infected babies. This report adds knowledge to a possible mechanism of transfer to the baby, i.e. via the placenta while pregnant, but women can remain reassured that pregnancy is not a significant risk factor for them or their babies with Coivd19.”

Prof Marian Knight, Professor of Maternal and Child Population Health, University of Oxford, said:

“This single case report identifies SARS-CoV-2 RNA in the placenta of a woman who was unwell with known COVID-19 in March 2020. Virus was detected in small amounts in the blood of her baby. The baby was born early because of concerns about his heart rate tracing prior to birth, which may have been due to the fact that his mother was unwell with COVID-19. The baby required help to breathe around the time of birth, but this does not appear to have been due to SARS-CoV-2 infection. It is unclear whether any of the subsequent symptoms and signs observed in the baby were due to SARS-CoV-2 infection, or due to events that occurred around the time of his birth.

“Among the many thousands of babies born to mothers with SARS-CoV-2 infection a very few have been reported to also have a positive test for SARS-CoV-2 – around 1-2%. As in this report, most babies do not appear to become severely unwell. It is still unclear whether the virus passes across the placenta; this report provides evidence that it may. However, when all current research is considered together, it does not suggest that virus crossing the placenta causes frequent significant illness in babies. The most important message for pregnant women remains to avoid infection through paying attention to hand washing and social distancing measures.”

‘Transplacental transmission of SARS-CoV-2 infection’ by Vivanti et al is published in Nature Communications.

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Christoph Lees: Co-Chief Investigator of the UKRI funded PAN-COVID UK & international registry

Prof Andrew Shennan: I have no conflicts.

Prof Marian Knight: I lead national surveillance into COVID-19 in pregnancy in the UK

None others received.