The hormone GDF15, produced in large quantities by the fetus, is the cause of nausea and vomiting that affects seven out of ten women in the first trimester of pregnancy and which becomes a serious medical problem in around 1% of women. pregnancies, according to international research led by Cambridge University (United Kingdom). The discovery, which is presented today in the journal Nature, opens the way to developing drugs to prevent or treat the disorder.
“We are closer to developing effective therapies to prevent other mothers from going through what I and many other women have gone through,” explains Marlena Fejzo, co-author of the research, in a statement. “When I was pregnant, I was so sick I could barely move. When I tried to find out why, I realized how little was known, even though nausea during pregnancy is very common.”
Fejzo suffered from hyperemesis gravidarum (HG), which literally means excess gestational vomiting and which affects approximately one in every hundred pregnancies (with a large margin of uncertainty ranging from 0.3% to 3% due to how little it has been studied). this disorder). HG, which can cause dehydration, nutrient deficiency and weight loss, is the main cause of hospitalization in the first trimester of pregnancy and, in extreme cases, leads to the death of the fetus.
The best-known recent case is that of the Princess of Wales, Catherine, who had to be hospitalized for HG in her first pregnancy, raising awareness of the disorder in the United Kingdom.
Fejzo, from the University of Southern California in Los Angeles, demonstrated in previous research that there is a relationship between the hormone gene GDF15 and the likelihood of suffering from HG. In the new research, in collaboration with the team from the University of Cambridge and 22 other institutions, she has provided evidence that the relationship between the hormone and the disorder is cause-and-effect.
“Several companies are evaluating antibodies against GDF15 or against its receptor GFRAL for oncological treatments, although at the moment none has expressed their desire to carry out a trial in HG,” Stephen O'Rahilly, director of the research, reports by email. “My lab is collaborating with others to develop an antibody for specific use during pregnancy.”
Before starting this project, researchers already knew that various organs and tissues can produce GDF15. The hormone acts in the brain stem, in the region of the nervous system that triggers nausea and vomiting. Chemotherapy drugs often cause nausea precisely because they raise the level of GDF15.
New research has shown that GDF15 increases in the first trimester of pregnancy and that more than 99% of the hormone circulating in the mother's blood comes from the fetus.
In addition, researchers have discovered what determines whether a woman has nausea and vomiting at the beginning of pregnancy and whether they are more or less intense. It depends, first of all, on the amount of GDF15 circulating in her blood: the more hormone there is, the more likely it is that she will feel unwell. And it depends, above all, on the level of GDF15 that she had before becoming pregnant: the lower her initial level was, the more likely it is that she will not be able to tolerate the strong increase resulting from pregnancy and that she will develop HG.
“The fetus produces the hormone at levels to which the mother is not accustomed. This tells us how we can prevent” the problem, says O’Rahilly. According to the researchers, a drug that gradually raises the level of GDF15 in the months before pregnancy could be an effective prevention. They have already tested this strategy successfully in mice, they report in Nature. The first candidates to receive preventive treatment would be women who have experienced HG in a previous pregnancy, O'Rahilly informs La Vanguardia.
“More than a third of women who experience HG decide not to become pregnant again. Some even terminate wanted pregnancies. I am sure that these women would be interested in a prevention strategy,” Marlena Fejzo states in an email.
On the other hand, a drug that blocks the action of the hormone GDF15 could become an effective treatment for HG once the disorder has started. The safety guarantees that would be required for this drug would be extreme to ensure that it does not cause harm to the fetus, as happened with thalidomide between 1957 and 1963, the researchers acknowledge. But “many women are already taking off-label medications to combat HG in the first trimester,” says O'Rahilly, who is developing an antibody against the GFRAL receptor for the hormone GDF15. “It will be relatively trivial to modify an antibody to prevent it from crossing the placenta and reaching the fetus.”
