May 22, 2020

expert reaction to study looking at placentas from COVID19-positive pregnant women

A study, published in the American Journal of Clinical Pathology, looked at placentas from COVID-19-positive pregnant women.

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

“This small study showed differences in the appearance of the placenta amongst some women with SARS-CoV-2 infection compared to women who had placental examination for other reasons.  It is unclear what proportion of women with infection had their placentas examined, whether the women had current or past infection, or whether they had other indications for placental examination, and therefore whether the differences observed could be causally linked to COVID-19 infection.

“Importantly, the majority of the women had normal term pregnancies and healthy babies, and thus the significance of these pathological findings are unclear.  Women should be reassured by the findings of much larger studies, which have not suggested higher risks of problems for babies due to placental complications.”

Prof Christoph Lees, Professor of Obstetrics, Imperial College London, said:

“This is a small study investigating pathological findings in the placentas of 16 women who either had tested positive for the SARS-CoV-2 virus, had recovered from COVID-19, or had the disease on admission.  The title ‘Placental Pathology in COVID 19’ is somewhat misleading as though 10 of the 16 patients were symptomatic, only 2 required oxygen and none were ventilated; hence some had asymptomatic viral infection, not COVID-19.  Nevertheless, the findings of maternal vascular malperfusion are of potential importance as this could suggest a mechanism by which fetal condition could be affected.  It is important to note that findings on pathological examination of the placenta do not, in many conditions, correlate with disease or compromise of the fetus and pregnancy outcome data for all but the most severely affected COVID19 pregnancies is reassuring.

“There are some methodological problems with the study that the authors rightly acknowledge: the numbers are very small on which to base any conclusions, and the actual pathological diagnostic differences between the placentas of COVID-19/SARS-CoV-2 and control cases are in the main marginal.  I would add that there appears to be no correction for the many comparisons that are made: statistically even if there were no differences, several of these comparisons would appear by chance to be significant anyway, so we don’t really know which are really different and which aren’t.

“Pathological examination of the placenta is well known to be very subjective in even the most experienced hands, and comparing to historical controls (as the authors have done) rather than contemporaneously collected placentas introduces a bias, especially so if there has been a subtle change in technique or diagnostic criteria over several years of placental collection.  The authors are quite correct to say that ideally a control group of placentas would be those where the mother had a flu like illness but was tested negative for SARS-CoV-2.  Furthermore, if the pathologist were blinded to the clinical details as in some pregnancy studies, ‘confirmation bias’ would be minimised.  I assume that this was not done as all the cases examined were sent for pathological testing on the basis of the mother’s condition.

“Hence with these caveats the interesting but preliminary findings of this study should be viewed as hypothesis-forming rather than definitive.”

Dr Edward Mullins, NIHR Academic Clinical Lecturer, Imperial College, said:

“It would be useful to know if any of the babies showed signs of distress before delivery, as the authors describe placental features that can be associated with adverse outcomes although happily all babies were born in good condition.

“The four pregnancies which were ongoing for 3-4 weeks after the woman was affected by COVID-19 resulted in well grown babies, born healthy at term.  This is in contrast to reports from the SARS pandemic, in which 2 out of 3 reported pregnancies where delivery was 5-7 weeks after onset of illness were complicated by fetal growth restriction in 2/3 pregnancies; the placentas in those situations during the SARS pandemic showed significant changes (areas with loss of blood supply and bleeding behind the placenta).

“Acknowledging the small numbers, this gives some reassurance that the growth of babies may not be affected by COVID-19 in the same way as it was in SARS.  However, further data is needed and studies such as the PAN-COVID registry will collect global data on the incidence of fetal growth restriction and stillbirth after COVID-19 infection.”

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

“This study in a small number of pregnancies suggests covid19 may influence how the placenta works by causing clotting.  However babies appeared well in spite of mothers being infected.  We know coronavirus can cause clots in blood elsewhere in the body and this may indicate potential concern for babies in infected mothers – but so far other studies have shown the vast majority of mothers and babies have good outcomes, even if infected.  If a mother is unwell the baby rarely gets the virus but may need to be delivered early to help treat the mother.  Serious outcomes are rare in mothers and babies.”

‘Placental Pathology in COVID-19’ by Elisheva D. Shanes et al was published in the American Journal of Clinical Pathology on Friday 22 May 2020.

DOI: 10.1093/AJCP/AQAA089

https://northwestern.app.box.com/s/x8xm2n8kefkn3iwln890ghdlofffowrn

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Marian Knight: “I am currently leading a UK national surveillance study of COVID-19 in pregnancy in the UK.”

Prof Christoph Lees: “I’m Co Chief Investigator for the UK PAN-COVID study.”

Dr Edward Mullins: “I am a co-PI on the PAN-COVID registry.”

None others received.