New study confirms: This hormone causes morning sickness and extreme pregnancy nausea
"There is a great deal of hope that a cure will eventually be found," says one of the researchers behind the study.
“I am very hopeful that exciting things are around the corner. The next few years are critical to understanding when these findings will be in the hands of patients,” Marlena Fejzo tells Science Norway.(Photo: Christina Gandolfo)
When Marlena Fejzo became pregnant with her second child in 1999, she became so ill that she was barely able to eat or drink.
Her doctor did not believe it could be as bad as she described. But she was eventually diagnosed with hyperemesis gravidarum – an extreme form of pregnancy sickness.
Fejzo ultimately ended up in hospital, but doctors were still unable to get enough food or fluids into her body.
"It really was like a form of torture," she told CNBC a couple of years ago.
In the end, doctors attempted to provide nutrition through a feeding tube, but by then it was too late.
Annonse
She lost the baby in the second trimester.
To prevent others from suffering
Fejzo, a geneticist at the University of Southern California, decided to find out what causes pregnancy sickness.
"I lost a baby to hyperemesis gravidarum in 1999 and have been working tirelessly ever since, so people do not have to suffer like I did," Fejzo tells Science Norway.
"That's why being at the point of actually seeing how decades of research may make a real impact on the lives of pregnant women and their families is so incredibly emotional and exciting for me," she says.
An indisputable finding
Fejzo found the answer to the mystery.
In a 2024 study, she and her colleagues concluded that nausea during pregnancy was caused by a hormone called GDF15.
The study was conducted on mice and genetic data from several thousand women.
"In this article, we have gathered data from all over the world. It's the largest study on this so far, covering nearly half a million pregnancies," says Marc Vaudel from the University of Bergen.
He has been responsible for the Norwegian part of the new study, which used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), one of the world’s largest health studies.
And the finding holds up.
"We show indisputably that GDF15 is the genetic cause of hyperemesis gravidarum," says Vaudel. "Nobody can claim that this applies only to Norway or only to Europe. The cause of this severe illness is rooted in genetics, and we see it in women all over the world."
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It's long overdue for extreme pregnancy sickness to be taken seriously, believes researcher and geneticist Marc Vaudel. “Having hyperemesis gravidarum is like being poisoned 24 hours a day, for several months,” he says.(Photo: Paul André Sommerfeldt)
A decisive blow to psychological explanations
"This completely changes the picture for extreme pregnancy nausea," says Hilde Erdal.
She studies hyperemesis gravidarum at the University of Bergen's Department of Global Public Health and Primary Care.
"It effectively puts an end to the idea that pregnancy sickness is caused by psychological reactions, a theory that has followed this condition throughout history," she says.
Last year, Erdal completed a PhD on the consequences of hyperemesis gravidarum in Norway.
Hilde Erdal researches hyperemesis gravidarum at the University of Bergen.(Photo: Private)
"There has been a lot of discussion about depression and nausea during pregnancy. Women have been told that it's normal and that they need to pull themselves together. But this is actually a physiological mechanism that's malfunctioning," she says, adding:
"You don't become nauseous because you're depressed. You become depressed from being so nauseous during pregnancy."
Many have to terminate the pregnancy
Every year, between one and three per cent of pregnant women in Norway are hospitalised with extreme pregnancy sickness. That amounts to about 600 women, according to Erdal.
Half of the women in Erdal’s study had thought about terminating their pregnancy because they were so ill. Nearly all reported feeling low or depressed.
Once they arrive at the hospital, the women receive the treatment that is available.
"But we see that some women receive no treatment at all before hospitalisation," Erdal says. "I worry especially about those who are not ill enough to be admitted. They remain at home suffering, even though they should have access to better care."
Current treatment mainly consists of anti-nausea medications along with ensuring that the pregnant mother gets enough nutrition and fluids.
Nearly 80 per cent of all pregnant women experience some nausea during pregnancy. Between 0.3 and 10.8 per cent suffer from nausea and vomiting severe enough to affect both the mother and foetus, the researchers write in the new article.
According to Vaudel, the condition is underdiagnosed.
"Around ten per cent of those hospitalised need to terminate the pregnancy because it becomes too dangerous," he says.
Multiple genes are involved
The new genetic analysis also points to other genes that may play a role – not just GDF15.
These genes could potentially explain why some women experience ordinary pregnancy sickness while others develop hyperemesis gravidarum.
"There may be factors beyond GDF15 that make the condition worse for some women than for others," Vaudel says. "We will investigate this further in future studies."
Now that the cause of hyperemesis gravidarum has been identified, work can begin on finding better treatments.
The mother’s own hormone levels matters most
Earlier research showed that pregnant women are influenced both by their own production of GDF15 and by the hormone produced by the foetus or placenta.
Women with low GDF15 levels before pregnancy are more strongly affected by the GDF15 produced by the foetus, while women who are already accustomed to the hormone are less affected.
By analysing genetic data from Norwegian women, Vaudel found that the mother’s previous exposure to GDF15 played the largest role.
This suggests that exposing women to GDF15 before they become pregnant could potentially reduce the severity of the illness, regardless of how much GDF15 the placenta produces.
"These findings give us real hope that new treatments can be developed," says Vaudel. "And yes, I know of several companies already working towards a cure."
Marlena Fejzo has spent more than 25 years searching for the cause of hyperemesis gravidarum after losing her own baby to the condition.(Photo: Matt Stokes)
Could a diabetes medication be the answer?
Research from the United States, Canada, and Denmark suggests that women taking the diabetes medication Metformin tend to experience milder symptoms during pregnancy than women who are not taking the drug. Metformin causes a slight increase in GDF15 levels in the blood, which may help mothers better tolerate the hormone produced by the foetus.
"This is probably not a miracle cure, but it's promising," says Vaudel. "We hope it could become a solution for women who want children but are unable to because of the severe nausea."
Other researchers are working on medications intended for use during pregnancy if symptoms appear.
Some of these treatments aim to suppress or block the hormone as it's released from the placenta, Vaudel explains.
"There is a great deal of hope that a cure will eventually be found," he says.
"More research is needed. But perhaps within the next decade we could have something available," Vaudel estimates.
Truly a major breakthrough
"This is very significant," says senior physician and professor Jone Trovik.
She is a specialist in obstetrics and gynaecology at Haukeland University Hospital and the University of Bergen.
"It was a major breakthrough when Marlena Fejzo first discovered it. She truly deserved to be named one of Time magazine's ‘women of the year’ in 2024. And it's also very exciting that we have a research community in Bergen helping to continue this work," says Trovik.
Although Trovik herself has never experienced hyperemesis gravidarum, she points out that many of the people researching the condition have personal experience with it.
"For a long time, this condition was overlooked and not taken seriously," she says.
Much of Trovik’s own research has focused on how to provide nutrition to severely ill pregnant women, including groundbreaking work involving feeding tubes placed directly into the stomach.
"Both the mother and the foetus can die if they do not receive adequate nutrition, or from severe malnutrition itself," she says.
Trovik is unsure whether the condition has one major cause and one major solution.
"Usually, several factors work together. But this gives researchers something concrete to work with. For hyperemesis research, this is truly a major step forwards," she says.
