Small study identifies placental abnormalities in pregnant women with COVID-19

A small study of pregnant women who were diagnosed with COVID-19 found that these women had placental abnormalities that can be associated with adverse outcomes.

The study, published in the American Journal of Clinical Pathology, included 16 pregnant women who tested positive for SARS-CoV-2 and delivered between March 18, 2020 and May 5, 2020.

Among the participants, 15 delivered during the third trimester and one experienced a miscarriage during the second trimester.

Researchers determined that pregnant women with COVID-19 were more likely than controls to have at least one feature of maternal vascular malperfusion, which has previously been associated with fetal growth restriction, preterm birth and stillbirth.

Although the major risk factors for maternal vascular malperfusion are gestational hypertension and preeclampsia, just one woman included in the study was hypertensive.

Therefore, researchers suggested that the findings warrant increased surveillance in women diagnosed with COVID-19.

Healio Primary Care spoke with study author Jeffery A. Goldstein, MD, PhD, assistant professor in the department of pathology at Northwestern University’s Feinberg School of Medicine, to learn more the long-term implications of these abnormalities and what additional research is needed in pregnant women with COVID-19.

Q: Why was this study needed?

A: If you look over the last 12 years, we’ve had two major infectious pandemics that have had a particular effect on pregnant women. In the 2009 H1N1 influenza, for whatever reason, pregnant women and [older women] who were not pregnant were more severely affected. And of course, with the Zika virus, the main thing that we think about is the microcephaly. Looking even further back to the 1918-1919 influenza pandemic, research done decades later shows that people who were in utero during the pandemic had higher lifetime rates of cardiovascular disease and lower total lifetime income. And so, we know that infectious diseases that affect society in general can have specific, different effects in pregnant women. When we started hearing about the coronavirus in Wuhan, before it was even clear it was going to come to the United States, [we] said, “We know that there’s going to be another big infectious wave that comes through the U.S., and that there’s a stark chance it involves pregnant women; what would a study of those patients look like, and what would we need to do to prepare now?” We wanted to be ready and to be able to have an effective research response.

Q: What placental abnormalities were identified in this study, and what are the health implications?

A: The major thing that we’re talking about are problems in the category of what’s called maternal vascular malperfusion. The placenta is the ventilator of the fetus. It is the first organ to form, and it does a lot of the functions for the fetus that other organs do for us. The fetus — through the umbilical cord — sends a large volume of blood into the placenta. The mother — through the vessels in the uterus — sends blood into the placenta. Those circulations don’t come into contact, but they’re set very close together. And so, you have exchange of oxygen and nutrients from the mother, and waste and carbon dioxide from the fetus. Maternal vascular malperfusion is a group of problems that we see in the placenta that deal with getting the blood from the mother into the placenta. More specifically, the problems we see in COVID-19 patients are with maternal blood vessels. Those vessels are normally wide and stay open, and we see some of the vessels are either more constrictive or they have muscle on them that will cause them to constrict. The other thing we see is actual injuries to those blood vessels — something that’s called atherosis and fibrinoid necrosis —where the wall of the blood vessel is injured, and you have an accumulation of blood clots and inflammatory cells. In general, maternal vascular malperfusion lesions on the placenta are things that we expect to see when moms have preeclampsia or other hypertensive conditions. In terms of consequences to the fetus, maternal vascular malperfusion changes are one of the sets of changes that we tend to see in stillbirths. That’s something, obviously, that we’re worried about a great deal. Some of the maternal vascular malperfusion changes have been associated with cerebral palsy, although not the blood vessel injury that we see in our study. These changes are actually associated with cardiovascular disease in the mothers long term. In the patients in our study, there was one patient who had gestational hypertension — somebody who was not previously hypertensive and who became hypertensive in pregnancy. Otherwise, none of our patients had preeclampsia or gestational hypertension, which makes us think that these changes are more related to the virus.

Q: What should physicians be looking for in pregnant women with COVID-19 receiving prenatal care?

A: Well, they should be receiving prenatal care, certainly. It’s very hard to go from an observational study like ours to practice changes, and I think one of the things that is really challenging is we don’t really have time to do the kind of interventional studies that we want because of the speed of this pandemic, and because the problems that are present now. There’s a lot of guess work and then checking our observations against the guesses. Most obstetricians would do more monitoring for women who had coronavirus even after they had recovered, so they would do an ultrasound to estimate the fetus’s growth to make sure that it’s staying at whatever curve it was on. There are also other monitoring strategies such as a nonstress test or a biophysical profile. These are noninvasive things that are done in the obstetrician’s office just to check on how the fetus is doing. There’s not the evidence base to support that, but obstetricians will have to make decisions based on what they see going on and what little information we’re able to provide them. I think that the information we provide them does support [the idea] that it makes sense to do some kind of increased monitoring in these patients.

Q: More research is needed on the potential effects of COVID-19 in pregnant women — where should this research focus?

A: There are a lot of areas of deficits. One that I think is the least obvious is that pregnant women need to be included in any trials of coronavirus vaccines, because the alternative to including them in the controlled trial is either doing wide-scale vaccination and just seeing what happens — a very large uncontrolled trial — or pregnant women not getting vaccinated. I think those are both much worse outcomes. In terms of informing practice, the areas that I see as “big picture” questions are what happens to patients who have coronavirus in the first and second trimesters. Most patients in our study, because of the timing of the epidemic, could only have gotten coronavirus in the third trimester. Their short-term outcomes were very reassuring. In terms of the second trimester, we had one patient that miscarried at 16 weeks. She did not have any symptoms [of COVID-19], and the placenta didn’t show the type of injuries we saw in other COVID-19 placentas, so is this someone who miscarried and then coincidentally had coronavirus, or is it someone who miscarried because they had coronavirus? One patient is not going to answer that question — that’s something that’s going to be answered on a larger scale. We know for some viruses, such as cytomegalovirus, the highest risk of causing injury to the fetus is in the first trimester. Zika virus is a similar situation because the first trimester is when organs are forming and basic patterns are being laid down, and so that’s when those things are most vulnerable to disruption. Otherwise, any sort of infections later would be more likely to cause problems with growth or injuries to pre-existing structures. I’m really interested in knowing the effects in the first and second trimester, and the long-term outcomes in these kids.