Taped atop a neatly arranged wooden desk in the corner of her bedroom, right at eye level, is a piece of paper that Marlena Fejzo has kept for 24 years.
It is a portrait of Fejzo at 31 years old during the worst moment of his life. His face and body are drawn with the lugubrious greens and yellows of illness, his sunken cheeks marked with tears. The colored pencil drawing, made by her sister in 1999, is the only image she has kept from that time. Fejzo, now 55, said the scant photographs her mother took “were too terrible” to keep.
Fejzo knew that some nausea and vomiting during pregnancy is normal. She experienced weeks of debilitating illness when she was pregnant with her first child, however, when she was expecting her second, she was so sick that she could not move without regurgitating.
She couldn’t go to work or take care of her child, or even swallow a teaspoon of water, let alone a bite of toast or a prenatal vitamin. Her empty gastrointestinal tract spasmed so violently and prolonged that she could not breathe.
“Every moment of life was torture,” he says.
For at least a month, Fejzo was unable to keep any food or drink down and received fluids through an intravenous tube. Her weight dropped from a scant 48 kilograms to 41, after which she was too weak to stand on a scale.
“I was starving,” he says, “and the doctor just kept trying higher doses of drugs and different drugs, but nothing helped.” Finally, his doctor agreed to give him liquid nutrients through a catheter that ran to a large vein near his heart, but Fejzo believes this was done too late. At 15 weeks gestation, the fetus’s heart stopped beating.
Fejzo was devastated. “All that incredible suffering for nothing,” she said.
Fejzo, who was then a postdoctoral researcher at the University of California, Los Angeles (UCLA), is now a research scholar in the Department of Obstetrics and Gynecology at the Keck School of Medicine at the University of Southern California.
During her pregnancy, she suffered from hyperemesis gravidarum , a disease whose characteristic symptoms include nausea and vomiting so severe and incessant that it can cause dehydration, weight loss, electrolyte imbalances, and require hospitalization.
This complication is rare, affecting about two percent of pregnancies, but its consequences can be devastating. In surveys, women have described their experiences with the disease in horrendous terms: “I was depressed and bedridden for twenty weeks. “I wanted to die,” wrote one; “I’m terrified of experiencing another pregnancy ,” said another.
Some wrote that they felt “miserable, hopeless” ; or alone and abandoned, with references to suicide . “I sobbed when she woke me up in the morning because I realized she was still alive . ”
In a recent survey of more than 5,000 patients with hyperemesis, 52 percent had considered terminating a desired pregnancy, and five percent had done so. 32 percent reported having thought about suicide .
Despite the seriousness of hyperemesis , as it is colloquially called, doctors are often slow to treat it. Jone Trovik, a gynecologist and professor of Clinical Science at the University of Bergen, in Norway, comments that, sometimes, they ignore the disease, considering it as a temporary discomfort or even a psychological disorder.
“Essentially, my doctor thought it was all in my mind,” Fejzo said. The doctor told her that women act sick during pregnancy to gain the empathy of their husbands and, later, he told her that her illness was a search for the attention of her parents, who were helping her with the illness. medical care of her.
The fact that the doctor blamed his own psyche for his suffering made Fejzo angry. So he decided to dedicate his life to discovering the true cause of the disease.
“It was so devastating what happened to me that I don’t want that to happen to anyone else,” she said.
Interrupted trajectory
Marlena Fejzo grew up a few miles from her current home, in the wealthy neighborhood of Brentwood, in Los Angeles, being one of four siblings in a home full of cousins and friends. She had a charming California childhood, Fejzo says, with regular trips to ski at Mammoth Mountain , hike in Yosemite National Park, and vacation in Palm Springs.
She graduated at the top of her class from the prestigious Harvard-Westlake School (then known as Westlake School for Girls ) and later studied applied mathematics at Brown University.
During her junior year at Brown, an introductory genetics class captivated her, and she decided to pursue a doctorate in that field at Harvard University, a surprise to her family of lawyers, language scholars, and musicians.
As a graduate student at Harvard, Fejzo discovered two genes involved in the development of uterine fibroids , and received national recognition for her research from the American Society of Human Genetics.
It was a rare honor for a young scientist, especially one working on a health problem that doesn’t affect men, said Cynthia Morton, a professor of obstetrics, gynecology and reproductive biology at Harvard Medical School and a doctoral advisor. by Fejzo.
“She was very hardworking and dedicated to her research,” Morton said. “She could do anything.”
In 1995, Fejzo began as a postdoctoral researcher in breast cancer genetics at the University of California, San Francisco, with her sights set on a full professorship and a career researching the genetics of conditions affecting women. But first, she and her husband wanted to start a family.
A few weeks after becoming pregnant with her first child in 1996, she began to suffer from constant nausea and vomiting (similar to the symptoms that would afflict her second pregnancy, although not as severe). Still, she could barely eat, she couldn’t work for eight weeks and, on two occasions, she required intravenous fluids to combat dehydration.
About 70 percent of pregnancies present with some degree of nausea and vomiting, but health professionals can be slow to differentiate normal “morning sickness” from hyperemesis, and to offer treatment for them.
This was Fejzo’s first experience with hyperemesis , although his doctor at the time never told him the name of his illness or offered him medicine to treat it.
In the second trimester she felt well enough to return to work and the rest of the pregnancy was normal. “When my son was born, she was ecstatic with happiness and everything was great, that’s why you do it again ,” Fejzo recalls.
Fejzo’s second pregnancy occurred two years later, in 1999, after she moved back to Los Angeles and accepted a second postdoctoral position at UCLA. She claims that it was then that she experienced the worst time of her life , which led to 10 weeks of serious illness and a miscarriage.
Fejzo’s sister, Melanie Schoenberg, now 45, a public defender for Los Angeles County, remembers seeing her at the end of that critical moment. Fejzo was in a wheelchair, too weak to walk and wrapped in a sheet, sobbing and shaking from the pain of the loss.
“He looked like a ghost,” Schoenberg said. Like a pile of bones.”
A poorly researched disease
At age 31, as Fejzo regained his strength, he made two decisions that would change his life. First, he stated that he would not attempt another pregnancy; His twins would be born later with the help of a surrogate. Second, she was determined to find the cause of the hyperemesis.
He searched hard in the medical literature to find clues. Why had she gotten so sick when most pregnancies had much milder symptoms? “Nothing was known. There were very few studies ,” said Fejzo.
Trovik, the Norwegian gynecologist, said hyperemesis has been under-researched and under-recognized, in part because about 70 percent of pregnancies have some degree of nausea and vomiting, which is usually not dangerous. She added that health care workers may be slow to differentiate between the more common “morning sickness” and the less common, but more serious, hyperemesis, as well as to offer treatment, including medications and nutrition.
Before intravenous fluids became routinely available in the 20th century, hyperemesis killed pregnant women often enough that medical literature included excessive vomiting as a reason for inducing abortion because of the danger it posed to the body. mother’s life Some experts believe that the death of the writer Charlotte Brontë in 1855 was most likely due to hyperemesis and not tuberculosis, as stated on her death certificate.
Today, deaths from hyperemesis are rare, but they do occur, as do serious complications. Electrolyte imbalances caused by excessive vomiting and dehydration can lead to arrhythmias and cardiac arrest . Malnutrition and a lack of thiamine, a type of B vitamin, can lead to a brain disorder called Wernicke’s encephalopathy , which can lead to miscarriages, brain injuries and death.
Hyperemesis is also linked to an increased risk of pregnancy complications , such as premature birth, preeclampsia , and blood clots.
In a recent study of more than 5,000 patients with hyperemesis in the United Kingdom, 52 percent had considered terminating a desired pregnancy, and five percent had done so. A 2022 study found that hyperemesis is one of the main predictors of postpartum depression .
Most babies born from pregnancies with hyperemesis are healthy, but recent studies have shown that they have a small increased risk of low birth weight , as well as cognitive , mental health , and behavioral difficulties in childhood (some researchers They are hypothesized to be effects that may be caused by malnutrition and stress in the womb).
For the last century, doctors have claimed, without evidence , that hyperemesis is a subconscious attempt at “oral abortion,” as if trying to vomit up a pregnancy ; a rejection of femininity; a product of sexual frigidity ; a strategy for taking a “ break ” from stressful domestic responsibilities; or a way to get attention, as the doctor had told Fejzo.
As a result, women have often been blamed and punished for their own illnesses. In the 1930s, patients hospitalized for hyperemesis “were denied the comfort of the vomit cup” and were forced to lie in their own vomit.
To this day, patients hospitalized with this disease are sometimes isolated in a dark room and prohibited from receiving visitors or access to their cell phones. This treatment has been based in part on the theory that hyperemesis is caused by a woman’s subconscious rejection of pregnancy, and that isolation would cause her to accept it , Philippe Deruelle, professor of obstetrics and gynecology at the University, said by email. from Strasbourg.
The practice is “misogynistic” and “indefensible ,” but it continues to occur at least occasionally in France and other European countries. In 2022, the College of Gynecologists and Obstetricians of France published new guidelines that included a statement condemning it.
Fejzo was outraged by the fact that her illness was said to have a psychological cause and the lack of effective treatments to help her. She thought that nothing would change as long as the true cause of the disease was unknown.
A decade of Fridays
When Fejzo returned to her lab at UCLA after her miscarriage, she mentioned to her boss, the chair of the Department of Genetics, that she wanted to find the cause of the hyperemesis. “He just laughed at me, like it was a joke ,” Fejzo said.
Unable to find a mentor interested in hyperemesis, Fejzo took a job studying ovarian cancer at university, a position she stayed in, mostly part-time, for 20 years. However, he began gathering research on hyperemesis during his evenings, weekends, and on Fridays when he was not working in the laboratory.
Her younger brother, Rick Schoenberg, 51, a statistician at UCLA, helped her create an online survey of hyperemesis patients, and the Hyperemesis Education and Research (HER) Foundation provided collaborators and grants. small to finance their work. In 2005, Fejzo also began partnering with obstetricians and gynecologists at the University of Southern California.
When I began to analyze the survey entries, “I immediately saw that the disease was hereditary,” Fejzo recalls. “Responses kept coming in where people said things like, ’Yes, my sister has it and my mom does too.’”
In 2011, Fejzo and his colleagues published their findings in the American Journal of Obstetrics and Gynecology . They found that women who had sisters with hyperemesis had a 17 times higher risk of developing the disease than those who did not have it, providing some of the first clear evidence that the disease could be passed from parents to children.
Fejzo knew that DNA analysis would be crucial to understanding the genetics of hyperemesis. So in 2007 he began collecting saliva samples from people who had had the disease and those who had not.
Every Friday for 10 years, he called study participants—more than 1,500 in total—to request their medical records and consent to take part in the study and send them saliva collection kits from their home.
However, Fejzo wasn’t sure how she would pay for genetic testing. Her grant proposals to the National Institutes of Health (NIH) were rejected. Since 2007, the agency has funded just six studies on hyperemesis, totaling $2.1 million .
That amount is small compared to the economic burden of the disease, says Kimber MacGibbon, executive director of the HER Foundation. (Actress Amy Schumer, who publicly documented the difficulties she faced with hyperemesis , sits on the foundation’s board of directors.)
MacGibbon said hospitalizations for hyperemesis are believed to cost patients and insurers about $3 billion a year, plus expenses for medications, home health care, lost work days and complications such as depression. postpartum. “The costs of that are just stratospheric,” he says.
’This is it’
Without the financial resources to analyze the saliva samples that were accumulating in the laboratory freezer, Fejzo discovered an alternative strategy when his older brother gave him a 23andMe DNA testing kit for his 42nd birthday.
After registering your kit, you received a standard email giving you the option to participate in the company’s research studies by completing an online survey and consenting to the use of your genetic data.
“I saw what they were doing, and I thought it was brilliant,” he says.
Fejzo asked 23andMe if she could include some questions about nausea and vomiting during pregnancy in her customer survey, and the company agreed. A few years later, she worked with the company to scan the genetic data of tens of thousands of consenting 23andMe customers, looking for variations in their DNA associated with the severity of nausea and vomiting during pregnancy. The results were published in the journal Nature Communications in 2018 .
A handful of gene mutations were marked as significantly different, but most surprising was one that generates a protein called Growth Differentiation Factor 15 (or GDF15). Fejzo had never heard of it, but as soon as he started reading about it I thought: ’Oh my God, this is it ,’ he recalls.
The GDF15 protein acts in part of the brain stem that inhibits appetite and triggers vomiting and had already been shown to cause appetite and weight loss in cancer patients. Blood levels of the protein naturally increase during pregnancy and have since been found to be even higher in people with severe nausea and vomiting.
Researchers speculate that GDF15 may have evolved to help pregnant women detect and avoid risky foods that could harm fetal development in the early months of pregnancy. However, in hyperemesis, this normally protective mechanism goes into overdrive, at least in part due to an abundance of GDF15, said Stephen O’Rahilly, director of the metabolic disorders unit at the University of Cambridge, who is now collaborating with Fejzo. in the research of this protein.
In a study published in 2022 , Fejzo and colleagues confirmed the link between hyperemesis and GDF15 in patients they recruited over a decade of working on Fridays. The analyzes were carried out free of charge by the biotechnology company Regeneron.
When that study was published, Fejzo wrote on Twitter : “The work to which I have dedicated my life is ready . ”
But it’s not over. He is watching closely as several pharmaceutical companies have begun testing GDF15-based drugs aimed at reducing nausea and improving appetite in cancer patients, with promising initial results .
A smaller number are working on similar drugs for hyperemesis, according to Fejzo. Among them is a newly created company called Materna Biosciences, which hired Fejzo as scientific director.
Fejzo explained that there are several obstacles to testing new drugs in pregnant women, but if done carefully, this step could improve treatment options for hyperemesis patients and definitively prove that the abundance of the GDF15 protein is the main cause of hyperemesis. the illness.
Additionally, Fejzo hopes to finally dismiss the idea that the illness is psychological.
“I would be devastated to see my daughters go through this without having tried to do everything in my power to make things better,” Fejzo concluded. “If I don’t continue with this, who will?”
Image : Maggie Shannon for The New York Times
