In COVID-19 Research, Pregnant Women Are Often Excluded

A call to close the knowledge gap

As scientists race to understand the effects of COVID-19 and search for potential treatments and vaccines, one group has been largely left out of research and clinical trials: pregnant women.

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This gap in knowledge will lead to immediate and long-term disparities in medical care for this important and “”scientifically-complex” population, increasing risk not just for pregnant women but also for their children and families, says Ruth Farrell, MD, MA. In an article published last month in Ethics and Human Research, Dr. Farrell and her colleagues, Edward Chien, MD, MBA, Oluwatosin Goje, MD, Stephen Bacak, DO, Charles Foster, MD, Steven Gordon, MD, and Hany Aly, MD, called not just for more COVID-19 research looking specifically at maternal and fetal health, but also for larger studies to be designed so that pregnant women can participate.

“It’s important that we recognize the need to include pregnant women in research, and not delay, because COVID-19 has been a serious public health threat for several months and data are just now emerging,” says Dr. Farrell, who serves as Vice Chair of Research in the OB/GYN and Women’s Health Institute at Cleveland Clinic.

She’s now helping lead a city-wide, multi-institution study investigating the impact of COVID-19 on pregnant women and their babies.

Research lagging

Physiological changes during pregnancy are known to often put this population at higher risk of infection from viruses (such as influenza) and medical complications from those infections. Also, these changes often mean that medications and other therapies work differently on pregnant women than on other populations. It is also known that many viruses will pass through the placenta and affect the baby.

And yet, “research on the impact of COVID-19 on maternal and fetal health is lagging,” says Dr. Farrell. “Thus far, there have been only a handful of studies about the possible effects of COVID-19 on pregnant women and their babies.”

The limited research that has been done on this population has indicated that COVID-19 may pose a significant risk. One early study from the CDC looked at 43 COVID-19 positive pregnant women who had been admitted to the hospital at or near term. Of this group, 86% had mild disease, 9.3% had severe disease, and 4.7% had critical illness and required intensive care.

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Newer research suggests that pregnant women with COVID-19 may be at significant risk of multiorgan failure and death. In a case study of nine pregnant women in Iran who were severely ill with COVID-19, seven women died, and all experienced more severe illness than household members who were also infected but not pregnant. In the same study, multiple patients required early delivery, resulting in complications for the neonates and multiple deaths. Three of the neonates were stillborn.

Left out of clinical trials

“Just as concerning, pregnant women are not being recruited for clinical trials for COVID-19 vaccines and treatments,” Dr. Farrell says.

Data from early studies of hydroxychloroquine as a potential treatment for COVID-19 did not include pregnant patients, even though the drug has previously been studied in pregnant women with autoimmune diseases and is not associated with any fetal or maternal complications. Now, many clinical trials studying the antiviral drug remdesivir in patients with moderate to severe infections specifically exclude pregnant women, as do many trials of the antiretroviral drugs lopinavir and ritonavir, even though this drug combination has been widely used in HIV-positive pregnant women.

On the vaccine side, all of the clinical trials now underway for potential COVID-19 vaccines exclude pregnant women. The disparity is not unprecedented, she notes, as pregnant women have historically been left out of clinical trials, delaying their access to medical care.

“Excluding pregnant women from these vaccine trials today means that they will have to wait months or even years longer than other groups for access to immunization,” Dr. Farrell says.

Closing the research gap

Even though other viruses like Zika and HIV are known to cross the placenta and infect the fetus, little is known about vertical transmission of COVID-19 during pregnancy and delivery, including how often it happens, and when it’s most likely to occur. Emerging data indicate that COVID-19 may in fact cross and infect the placenta, which raises concerns about vertical transmission.

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The collaborative study between Cleveland Clinic, University Hospitals Cleveland Medical Center, and Cleveland’s MetroHealth System, in conjunction with Case Western Reserve University and the NIH, will investigate this issue. Key questions include when transmission might occur during pregnancy, and what the effects are for both maternal and fetal health.

Researchers are now recruiting pregnant women who’ve tested positive for COVID-19 at any time in their pregnancy. Researchers will collect different samples  from study participants during labor and delivery, and look for signs that the virus is present — or that it might have been in the past. All of these samples will be collected as part of routine care and, will not pose any additional risks to the pregnant woman or her baby.

“We’re just one team, but we need more initiatives and more scientific collaboration, both in this country and globally, to truly understand the impact of COVID-19 on pregnant women,” says Dr. Farrell. Research should look across the different groups within this population, she adds.

“Pregnant women are not just one unified population,” she says. “They are diverse communities and diverse patient populations, each of which will need specific approaches.” This will be important to understanding the true impact of COVID-19, not just among all pregnant women but, particularly, the pregnant women and their children who live in our community.