Pregnancy and COVID: Study probes possible long-term effects

In the first week of April 2020, maternal fetal medicine specialist Dr. Anna Euser was covering the inpatient service at UCHealth University of Colorado Hospital. It was the very early days of the COVID-19 pandemic, and all elective procedures had been shut down, leaving most of the hospital’s operating rooms eerily quiet.

By contrast, the Maternal Fetal Medicine service was operating at full capacity “because pregnancy couldn’t stop for COVID,” Euser said. She recalled seeing many women sickened by the virus, including one who required delivery by Cesarean section while she was intubated.

“It was the first time we had done a C-section on somebody, specifically due to how sick they were with COVID, to remove the baby from the situation,” Euser said.

She later reflected on how little she and other providers who cared for pregnant mothers at that time knew about the budding disease. Yet they didn’t have the luxury of waiting to gather more information about it. They had to take whatever steps were necessary to care for their patients and the unborn children they carried.

“The pregnant woman is still an adult who needs to be taken care of,” Euser said. “And ultimately fetal health is tied to maternal health.”

Euser, who was herself in the midst of completing in vitro fertilization while assisting another prospective mother with a precarious delivery, gave birth to daughter Nell in late January 2021. She was a little less than halfway through her second pregnancy in September 2022 when she, too, was diagnosed with COVID-19.

An early and vocal proponent for protecting pregnant women from COVID-19 with the vaccine that first became available in December 2020 and the subsequent boosters, Euser endured only mild symptoms and gave birth to a second healthy daughter, Tess, last March. But that happy outcome hasn’t stunted her concerns about the threat COVID-19 may pose for pregnant women. It spurred her to join a multisite clinical trial now underway that aims to explore the possible ongoing consequences of COVID-19 infection during pregnancy on mothers and their babies.

Pregnancy and COVID study includes those who have and haven’t had the virus

The study is an arm of the National Institutes of Health-funded RECOVER initiative, which is investigating long COVID and its wide-ranging, persistent symptoms from a variety of perspectives.

The University of Colorado Anschutz Medical Campus is partnering with the University of Utah through the national Maternal-Fetal Medicine Units Network to enroll women in the trial, said Dr. M. Camille Hoffman, principal investigator (PI) for the University of Colorado site. Hoffman is a professor of Maternal Fetal Medicine in the University of Colorado School of Medicine departments of Obstetrics & Gynecology and Psychiatry. The national trial is enrolling both women who had COVID-19 during pregnancy and those who did not, Hoffman said.

The Colorado researchers were able to enroll plenty of participants who had COVID-19 while pregnant, but they are actively seeking women who have been pregnant in the last three years and have never had COVID, said Jocelyn Phipers, director of Perinatal Research for Obstetrics & Gynecology at CU.

Every six months, participants will complete questionnaires, share vital signs and medical histories and submit blood, urine and sometimes stool samples for lab work, Phipers said. If the lab work shows abnormal results, participants will get additional testing, such as ultrasounds, she added. The trial will follow the women for four years.

The trial will also enroll children born to mothers who contracted COVID-19 during pregnancy, said Hoffman. Providers will see the youngsters at Children’s Hospital Colorado for questionnaires related to the child’s health history, as well as optional blood work and neurodevelopmental assessments to evaluate the effects, if any, of their mothers’ infections on their development, Phipers said. The trial will follow the children for three years.

Phipers added that maternal participants who have never been diagnosed with COVID-19 will receive antibody testing. Those who test positive will be kept in the trial but will be in the group of participants who actually have had COVID, she said, giving them “an opportunity to garner information about their own medical health and their child’s.”

A much-needed investigation of the toll of maternal COVID-19 infection

With the tide of the COVID-19 pandemic finally receding, the study is part of a wide-ranging effort by the medical community to understand the toll left in its wake. During the early stages of the pandemic, Hoffman said, providers were most concerned with the elevated risk COVID-19 posed to mothers.

Their worries were well-founded. A study from the Centers for Disease Control and Prevention showed that the maternal mortality rate rose sharply between the hard-hit COVID years of 2020 and 2021. The number of maternal deaths related to COVID nearly quadrupled during the same period.

There were also questions about whether COVID-19 might exacerbate well-established health threats for pregnant women, including hypertension and preeclampsia, a condition that increases blood pressure to dangerous levels, Hoffman said. Both hypertension and preeclampsia can decrease the amount of oxygen supplied to the placenta, the fetus’s vital lifeline, Hoffman said.

Some early research supported the suspicion. A 2021 study found that COVID-19 infections early in pregnancy increased the risk of both hypertension and preeclampsia. Another study published in JAMA Pediatrics the same year concluded that COVID-19 in pregnant women “substantially increased” their risk of mortality, preeclampsia, preterm birth and other complications.

These serious worries for women’s health took an unexpected turn with the emergence of the Delta variant of the virus midway through 2021, Hoffman said. Symptoms for infected mothers were milder but stillbirths, preterm births, and low birth weights were more frequent.

“All we could attribute this fairly dramatic difference in pregnancy outcomes to was COVID,” Hoffman said.

Investigating the role of inflammation

Hoffman suspects the culprit in COVID-19 health issues for moms and babies is a powerful inflammatory response triggered by the SARS-CoV-2 virus – even when the symptoms are very mild or even silent.

“We knew from early on in [the pandemic] that COVID increased the risk of blood clots and a lot more inflammatory conditions,” Hoffman said. She noted that inflammation is a well-established marker for and driver of preeclampsia and added that labs she’s seen show high levels of inflammatory markers even in women who had only mild symptoms of COVID during their pregnancies.

“It is unsettling and impressive to me to see that,” Hoffman said. “It speaks to me that COVID is a virus that really revs up the immune response and inflammatory system. We worry about the metabolic consequences of it for the mom – and for any adult or kid – but also for the fetus.”

With its enrollment of the children born to study participants, the study could increase understanding of those consequences and head off long-term health challenges, Hoffman said.

“The earlier you recognize deficits in a child, the earlier you can intervene, which is known to improve outcomes,” she noted.

Volunteering to increase understanding of COVID-19 and pregnancy

Anna Euser said she’s not worried that her mild case of COVID while pregnant threatens the health of infant Tess. She notes that there was even an upside to getting infected in that she passed on protective SARS-CoV-2 antibodies to Tess through the placenta. Her delivery was uncomplicated, but she said she plans to bring in Tess in as a participant in the pediatric arm of the study.

“My guess is there will be no major effects, but if there are, I want that to be discovered as well,” Euser said. “Anything I can do with my children and myself to get better data is helpful.”

More broadly, Euser said she welcomes the opportunity to contribute to deepening understanding of a disease that has affected her as a woman, a mother and a health care provider.

“I feel as someone who understands the medical side of things, it’s really important to be part of gathering information and research about something as new as COVID,” Euser said. “If there are ways I am able to help, both as a personal example and more formally as a study participant, and to contribute to data to give to patients, that’s only a positive.”

For more information on the trial, contact Jocelyn Phipers at 303-724-7807 or visit Study | Search Results | Research Studies | School of Medicine | University of Colorado (cuanschutz.edu).