Why a Life-Threatening Pregnancy Complication Is on the Rise

It’s impossible to pinpoint when ob-gyns sensed that preeclampsia—a surge in blood pressure in the later stages of pregnancy that endangers both mother and baby—was increasing among their patients during the COVID pandemic. Preeclampsia affects some two hundred thousand pregnant people in the U.S. per year, and case numbers had been ticking steadily upward for a couple of decades (although some of this increase was attributable to improvements in how doctors diagnose the disease). But this seemed to be more than an uptick; this felt like a jump. Physicians describe not a eureka moment but a creeping realization, a longitudinal hunch. Group texts and Facebook forums lit up with talk of more patients whose labor had to be induced early owing to blood-pressure spikes; doctors told one another that they were seeing more preterm births and more stillbirths. “Right away, there was chatter about more hypertension and preeclampsia being noticed in the COVID hot spots,” Jennifer Jury McIntosh, a maternal-fetal-medicine specialist in Milwaukee, said.

The coronavirus attacks endothelial cells, which form the cellophane-like lining of blood vessels. Ob-gyns began to suspect that the virus affects the vessels of the placenta, which ferries oxygen and nutrients to the fetus. Inflammation, clotting, and other vascular damage in the placenta put the baby at risk for not getting enough oxygen; the baby’s growth may slow, or stop. The same damage is also believed to trigger preeclampsia and other hypertensive disorders in the mother, which can impair the liver and kidneys, trigger strokes, and even result in death. The closest thing to a surefire remedy is to deliver the placenta, which means inducing labor. In the earliest and most severe cases, which occur before or at the threshold of fetal viability, the treatment for preeclampsia is termination of the pregnancy.

“We were seeing an increase not only in preeclamptic patients but the severity of preeclampsia,” Alison Petraske, an ob-gyn in Princeton, New Jersey, said. These outcomes, Petraske went on, appeared to have a common denominator. “It’s a general feeling: preeclampsia, intrauterine-growth restriction, later miscarriages, stillbirths—all of it is placental.”

More than two years into the pandemic, the general feeling is solidifying into data. A study of more than three hundred thousand women in England, conducted in 2020 and 2021, showed that patients who were infected with COVID when they gave birth had higher rates of preeclampsia, emergency C-sections, preterm birth, and stillbirths. Similar findings were reported in a National Institutes of Health study of pregnant people in the U.S. who experienced severe COVID symptoms and also by the INTERCOVID study, which involved more than two thousand pregnant women in eighteen countries, and which showed a strong correlation between COVID infection and preeclampsia and preterm birth, especially for first-time mothers. That study also indicated that COVID infection nearly doubled a pregnant person’s chances of developing HELLP syndrome, an extreme variant of preeclampsia that ravages the liver. Perhaps the most startling study examined sixty-four stillbirths and four neonatal deaths—all of which involved unvaccinated mothers—across twelve countries, and found that COVID could lead to a novel inflammatory disorder, SARS-CoV-2 placentitis, which causes “widespread and severe placental destruction.”

Brigham and Women’s Hospital, in Boston, has maintained a biobank of blood and urine samples from pregnant volunteers, collected at various stages of gestation, since 2006. The specimens, kept in deep-freeze storage, serve as a research platform for studying all manner of pregnancy complications. Thomas McElrath, a maternal-fetal-medicine physician at the hospital and a professor of epidemiology at Harvard, told me that the baseline rate of preeclampsia among these subjects has typically been five to six per cent. But, since 2020, that number “has gone up to over nine per cent and is approaching ten per cent,” he said. “It isn’t just anecdotal—at least at our institution, we are actually seeing this happen.”

The likelihood of hypertensive complications in the presence of COVID appears to rise according to the severity of the infection, how early it was contracted during the pregnancy, and whether the patient is vaccinated. Preëxisting conditions that leave patients vulnerable to both COVID and preeclampsia—obesity, diabetes, chronic hypertension—likely have a compounding effect: one study estimated that having one or more of these conditions along with COVID increased a patient’s odds of preeclampsia by a factor of four.

The link between the coronavirus and preeclampsia is of particular concern in the U.S., a country that is unusually terrible at managing both COVID and pregnancy complications. The U.S. has the largest share of COVID deaths worldwide. Among developed nations, it ranked last for maternal mortality; according to the Centers for Disease Control and Prevention, about a third of mothers who died during a hospital delivery in 2019 had a documented hypertensive disorder. And, for infant mortality, the U.S. placed thirty-third out of thirty-six industrialized nations. These numbers predate COVID, of course—as dire as they are, they still trail behind what physicians are seeing in their offices and in their wards. Rakhi Dimino, an ob-gyn based in Houston, is a medical director of operations for the Ob Hospitalist Group, overseeing around twenty hospitals in Texas, Louisiana, Oklahoma, and Illinois. She is also the chairwoman of the board of directors of the Preeclampsia Foundation, a nonprofit that raises awareness of the disease’s symptoms and possible treatments. “Many of our doctors have been saying, ‘I’ve never seen so many third-trimester stillbirths so close together,’ ” Dimino told me. “It affects you terribly. That wail of a mother when she’s lost her baby is something that you don’t forget.”

She recalled a patient whose pregnancy had reached full term, and who came to see her a day before she was to be induced. “There was no heartbeat. Having to look at her and say that we missed it by one day . . .” Dimino paused. “It was horrific. Horrific. And I remember—she wasn’t the only patient that day who had a stillbirth at term. And these babies, when you deliver them, they look like a normal newborn, only when they deliver they don’t take that first breath. They look perfect.” Dimino has been practicing medicine for sixteen years. In the past year and a half, she said, “I’ve seen more of that than I have in my entire career.”

Human beings seem to be the only species—with the possible exception of gorillas—that gets preeclampsia. That lonely distinction may offer clues to the precise cause of a still enigmatic disease. “One area of speculation is that the human placenta is unique in how very aggressive it is in its search for oxygen and nutrients,” McElrath said. “It will embed itself more deeply within the lining of the uterus than is the case for all other forms. That level of invasiveness is needed for the growth of a highly developed brain and central nervous system—and that is, of course, our evolutionary advantage. You need that brain, that very energy-demanding organ, to grow quickly before it exceeds the mother’s ability to pass this large-headed baby through her pelvis.”

The earliest, most severe form of preeclampsia, which strikes around the midpoint of pregnancy, is believed to be related to a failure of the fetal cells, known as trophoblasts, “to invade the maternal vascular system and remodel the maternal blood vessels within the uterine wall, making them much wider,” McElrath said. These vessels must take on as much as a hundred times more blood volume in pregnancy. “In the wider form, the blood flows more slowly. If it remains narrow, it’s like if you put your finger over the garden hose—it shoots out with more force. That force can damage the undersurface of the placenta.”

It was Aristotle who likely first grasped the basic function of the placenta (“the vessels join on the uterus like the roots of plants,” he wrote, “and through them the embryo receives its nourishment”) and Leonardo da Vinci who correctly guessed that the fetus, through the placenta, had a vascular system that was separate and discrete from that of the mother, a fact that was not conclusively established until the eighteenth century. But instruments for measuring blood pressure were not developed until the late nineteenth century, when physicians soon drew correlations between high blood-pressure readings and the likelihood of seizures during or after childbirth, often presaging death. Preeclampsia was definitively established as a syndrome in the nineteen-twenties, the decade in which Lady Sybil died gruesomely of it on a memorable episode of “Downton Abbey” that first aired in 2012. (McElrath told me that the episode raised preeclampsia’s profile, making it easier for doctors to talk about the disease with their patients. “ ‘Downton Abbey’ did a service to those of us in the field,” he said.) Diagnostic criteria for preeclampsia that were laid down in the nineteen-forties—thresholds for blood pressure and for elevated protein levels in a patient’s urine—are still in use today. But it was not until the eighties that James Roberts, of the University of California, San Francisco, in collaboration with several colleagues, began publishing groundbreaking research that linked preeclampsia to endothelial injury.

An old saying among ob-gyns, which is mostly still true, is that the cure for preeclampsia is delivery: of the baby, of course, but also of the placenta that seems to cause the condition in the first place. First-time mothers may be surprised to learn that, having defied physics and geometry by pushing out a baby, they must then participate in the anticlimax of pushing out what amounts to a flank steak. I dimly recall, after my first child was born, an excited nurse holding up our apparently unusually beautiful placenta. The umbilical vessels formed a tree of life, she told me, her fingers tracing its roots and branches in wonderment. “Wow,” I think I said. Other new mothers are better at expressing their enthusiasm, notably during the two-thousand-tens vogue for repurposing the placenta: cooking and eating it, liquefying it into a skin-care product, or powdering it for use as a vitamin supplement. In a 2013 episode of “Keeping Up with the Kardashians,” Kourtney pretends to serve one to her mostly unwitting family as a roast dinner. (“Is it a brisket?” Kris asks.)

Some risk factors for preeclampsia correlate with affluence: older mothers, especially older first-time mothers, are more likely to get it, as are mothers who have undergone I.V.F., and these characteristics correlate with higher income levels. To a far greater extent, though, preeclampsia in the United States is tied to the wages of structural racism and poverty. The odds that a Black woman in the U.S. will experience preeclampsia is one in eight. Black women are three times more likely than white women to die in childbirth. America’s scandalous infant-mortality rate is “largely driven by the deaths of black babies,” as Linda Villarosa wrote in the Times in 2018; the same can be said of the maternal-mortality rate and Black mothers. Black women are more likely to suffer from comorbidities associated with preeclampsia—including obesity, diabetes, and preëxisting hypertension—and less likely to have access to good prenatal care. They are also overrepresented among COVID-related deaths and less likely to be fully vaccinated than white women.

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