“I’ve been working on this for 20 years, and yet there are still reports of women dying from this and women being mistreated,” said Dr. Marlena Fejzo, a geneticist at the University of Southern California Keck School of Medicine and a co-author of the new study.
She knows the pain of the condition firsthand. During her second pregnancy, in 1999, Fejzo was unable to eat or drink without vomiting. She rapidly lost weight, becoming too weak to stand or walk. Her doctor was dismissive, suggesting she was exaggerating her symptoms to get attention. She was eventually hospitalised and miscarried at 15 weeks.
Fejzo said she asked the National Institutes of Health to fund a genetic study of hyperemesis but was rejected. Undeterred, she persuaded 23andMe, a popular genetic testing company, to include questions about hyperemesis in surveys of tens of thousands of customers. In 2018, she published a paper showing that customers with hyperemesis tended to carry a variant in a gene for GDF15.
Hormones are chemicals that send messages across the body. GDF15 is released by many tissues in response to stress, such as an infection. And its signal is highly specific: Receptors for the hormone are clustered in a part of the brain responsible for feeling sick and vomiting.
In the new study, Fejzo and collaborators at the University of Cambridge in England measured the hormone in pregnant women’s blood and analyzed the genetic risk factors for hyperemesis.
The researchers found that women experiencing hyperemesis had significantly higher GDF15 levels during pregnancy than did those who had no symptoms.
But the hormone’s effect seems to depend on the woman’s sensitivity and exposure to the hormone before pregnancy. The researchers found, for example, that women in Sri Lanka with a rare blood disorder causing chronically high levels of GDF15 rarely experienced nausea or vomiting in pregnancy.
“It completely obliterated all the nausea. They pretty much have next to zero symptoms in their pregnancies,” said Dr Stephen O’Rahilly, an endocrinologist at the University of Cambridge who led the research.
O’Rahilly hypothesised that prolonged exposure to GDF15 before pregnancy could have a protective effect, making women less sensitive to the sharp surge in the hormone caused by the developing fetus.
In lab experiments, the scientists exposed some mice to a small amount of the hormone. When given a much larger dose three days later, the mice did not lose their appetites as much as did animals that were not given the earlier dose — showing a robust effect of desensitization.
The findings offer hope for better treatments for hyperemesis, experts said. Patients with hyperemesis could one day take medications to block the hormone’s effects in the brain, if clinical trials were to find the drugs safe in pregnancy. Such medications are being tested in trials of cancer patients with a loss of appetite and vomiting also caused by GDF15.
It may even be possible to prevent the condition. Women who are at risk, such as those who experienced severe nausea and vomiting during a previous pregnancy, could be exposed to low doses of the hormone before becoming pregnant. (One diabetes drug, metformin, increases levels of GDF15 and is already prescribed to aid fertility in some patients.)
The new study is powerful because it offers genetic proof of a causal relationship between GDF15 and the disease, said Rachel Freathy, a geneticist at the University of Exeter who was not involved in the study. That will help the condition gain greater recognition, she said.
“There is kind of an assumption made by many people that women should just be able to cope with this,” Freathy said. With this biological explanation, she said, “there will be more belief that this is a real thing rather than something in somebody’s head.”
This article originally appeared in The New York Times.
Written by: Azeen Ghorayshi
©2023 THE NEW YORK TIMES
