Pregnancy complications spiked during pandemic. No one knows exactly why.

Lauren Phillips, a 32-year-old attorney from Brooklyn, had an easy pregnancy. Her vitals remained perfect, she felt great eating only vegan food, and was able to walk three miles a day throughout. The only blip was that despite being thrice vaccinated and meticulous about masking, she got infected with the coronavirus in her second trimester.

At the time, it didn’t seem like a big deal—”just like a mild cold”—and her pregnancy proceeded without incident until she gave birth to a healthy eight-pound baby boy in April. The trouble began a few days later.

She was at home nursing her son when she felt what she called a “pulse” shake her body and by the time she made it to the emergency room, her blood pressure had rocketed to a dangerous 160/116. Phillips didn’t know it then, but she had preeclampsia, a little understood complication of pregnancy that each year results in more than 70,000 maternal and 500,000 fetal deaths worldwide. Rates of the illness had been rising steadily in the United States for years, but during the pandemic, the number of cases jumped, according to doctors. No one knows exactly why.

The mystery of preeclampsia cases like that of Phillips is part of the growing pool of information scientists are sorting through when it comes to the impact of the coronavirus on reproductive health, from a woman’s menstrual cycle and fertility down to possible effects on a baby’s development.

Ilhem Messaoudi, a professor of immunology at the University of Kentucky, said she and many of her colleagues have been taken aback by the extent to which pregnancy has been affected by the pandemic. Like many researchers, she had initially thought of COVID-19, the disease caused by the SARS-CoV-2 virus, as a respiratory illness and did not expect it to impact reproductive organs.

Instead, she and other pregnancy experts have spent the past few years scrambling to understand spikes in maternal complications—first reported anecdotally then verified in several large studies—including an extremely small but nonetheless alarming group of unusual stillbirths. “I was naive,” Messaoudi reflected. “Now I wonder, ‘What else have we been missing?'”

It will be decades before we know the extent of the coronavirus’s effects on human health. But now, more than 2 years and 9 months since it appeared—a period in which millions of pregnant people have been infected with the virus at least once—researchers have noted some positive signs, some worrisome ones, and many other data points they still aren’t sure how to evaluate, especially since it’s difficult to disentangle the impact of maternal stress during the pandemic from the devastation of the virus itself.

The coronavirus is not the first virus to have ripple effects that may impact pregnancy and childbirth. During the 1918 flu pandemic, rates of stillbirth soared, and babies born during the height of the disaster suffered from higher rates of cardiac and other health issues as adults. In 2015, Brazil and numerous other countries reported an association between infection with the Zika virus and microcephaly, a rare neurological condition that results in an infant’s head being abnormally small.

Among the key findings so far about SARS-CoV-2—by many accounts the most studied virus ever to infect humans—are that fertility appears unaffected by either infections or vaccines. Periods may shift in women after the vaccine but only slightly so and the change appears to be only temporary.

But there is more reason for concern with pregnancy itself. While the vast majority of people who are infected do not experience complications, the risk of preeclampsia and other severe issues has been documented to be much higher with infection.

The biological mechanisms are still unclear, but researchers say they likely start with changes in the blood and immune system of the mothers. Pregnancy can be both magical and brutal as it transforms a person’s body to support another life. Much of the stress is on the heart and circulatory system, with blood volume surging by 30 percent to 50 percent, and the heart growing to pump more blood.

The coronavirus, it turns out, can have a profound impact on that same system. The virus attaches itself to what are known as ACE2 receptors involved in regulating blood pressure and inflammation, and throughout the pandemic, doctors have found that in some patients, the disease can lead to hundreds of microclots in blood vessels, all of which can have a range of effects on the mother and developing baby.

For the first nine months of their being, humans are cocooned inside an organ in their mother’s uterus known as the placenta that provides oxygen and other nutrients. Back in spring 2020, when health officials still called COVID-19 a respiratory disease, the idea the virus could wreak damage on that seemed far-fetched.

Then, last fall and winter, Amy Heerema McKenney, a Cleveland Clinic pathologist whose job involves figuring out why some babies die, began receiving eerily similar reports of stillbirths. The cases seemed to appear out of nowhere and in rapid succession.

Almost as soon as she began looking into them, Heerema McKenney recalled, she became “pretty panicked.” A normal placenta is spongy and dark, reflecting the nourishing blood flowing through it. The ones she was looking at in her lab from the mothers who lost their babies were like nothing she had ever seen before: firm, scarred and more of a shade of tan.

“The degree of devastation was unique,” she said. Flipping through case files, she noted that most of the women were in their second trimester, unvaccinated or only partially vaccinated, and infected with the coronavirus within a two-week window before their pregnancies ending. Heerema McKenney herself saw fewer than 20 potentially coronavirus-related stillbirths over about six months.

But her findings matched up with cases colleagues were seeing in other parts of the world. And they also echoed those in a paper from Ireland that looked at seven cases—six stillbirths and one second-trimester fetal death in pregnant people infected with the coronavirus—resulting from what the authors called “a readily recognizable pattern of placental injury.” She said, “That’s when we realized we were all looking at the same thing.”

A report from the Centers for Disease Control and Prevention involving 1,249,634 deliveries from March 2020 to September 2021 similarly documents a link. “Although stillbirth was a rare outcome overall, a COVID-19 diagnosis documented during the delivery hospitalization was associated with an increased risk for stillbirth in the United States, with a stronger association during the period of delta variant predominance,” the researchers wrote.

They theorized that a reduced blood flow to the placenta, along with inflammation from a coronavirus infection, “might, in part, explain the association between COVID-19 and stillbirth.” No sooner had Heerema McKenney and other researchers around the world begun pooling data and discussing how to react, the delta wave receded, and when omicron arrived, the cases simply disappeared.

While the stillbirth cases stunned the medical community due to their clustering within a short period and their impact on the placenta, a surge in preeclampsia presents a much larger public health threat.

Preeclampsia, a leading cause of maternal death across the globe, usually begins with small signs like high blood pressure, bubbly urine or vision changes but can progress rapidly to send a person’s entire body into crisis. It typically occurs midway through pregnancy, after about the 20th week, in roughly 2 to 6 percent of pregnant people in the United States.

“It’s a progressive condition,” said Patrick Ramsey, a professor of obstetrics and gynecology at the University of Texas Health Science Center at San Antonio, and chief of its division of maternal-fetal medicine. While most cases resolve when the baby is delivered or the pregnancy ends, there is no clear treatment in the meantime and the condition can result in organ failure and death.

During the pandemic, pregnant people infected with the coronavirus—whether symptomatic or not—were found to have a 60 percent greater risk of preeclampsia than those who were not infected, according to a number of studies. They also experienced higher rates of other complications, ranging from preterm birth and infection, to dying within six weeks of the pregnancy ending.

Aris Papageorghiou, a professor of fetal medicine at the Oxford Maternal and Perinatal Health Institute in the United Kingdom, who participated in the research, said no one knows exactly why the coronavirus can affect pregnancy so severely. But one theory is that the virus may “unmask” or exacerbate underlying issues that already put some women at risk for preeclampsia or inflammatory disease.

He said previous coronaviruses, including SARS-CoV-1, which hit Asia in the early 2000s, and MERS-CoV, which caused outbreaks mostly in the Middle East from 2012 to 2015, were also associated with greater maternal complications.

Messaoudi’s research findings bolster his hypothesis. In her study of the placenta and cord blood of infected pregnant people, she found what she calls “disturbances”—or changes in infection-fighting T cells and other immune system changes—that might have long-lasting consequences. She and her colleagues described the differences as a “remodeling of the immunological landscape” or “immunological scars.”

These signs showed up even in people who were asymptomatic or had mild COVID-19 symptoms, and Messaoudi wonders whether the immune responses might be part of what caused changes in the placenta linked to stillbirths.

“I think I should have known,” she said, “but I was still surprised by the magnitude of that impact.” For some women who have experienced preeclampsia, the complications seemed to come out of the blue.

In the case of Phillips, the Brooklyn woman who developed the condition after giving birth, doctors stabilized her after a few days, but she remained on heavy blood pressure medication for five more weeks. Today, she worries about other pregnant people who may get COVID-19 without being told about the link with preeclampsia.

“Right now we’re not doing enough. Maybe if people knew more about the risks they would be behaving differently,” she said, adding that she continues to have “lingering worries about what damage this may or may not have done” when it comes to future pregnancies since she and her husband would like to have more children.