by The nausea and vomiting that often characterizes the first trimester of pregnancy is mainly caused by hormones, according to a study published Wednesday in the journal Nature. Researchers said the discovery could lead to better treatments for morning sickness, including rare, life-threatening cases.
The study confirms previous research that showed the hormone, called GDF15. The researchers found that the amount of hormones circulating in a woman’s blood during pregnancy – as well as her exposure to it before pregnancy – drives the severity of her symptoms.
More than two-thirds of pregnant women experience nausea and vomiting in the first trimester. And about 2% of women are hospitalized for a condition called hyperemesis gravidarum, which causes incessant vomiting and nausea throughout the entire pregnancy. The condition can lead to malnutrition, weight loss and dehydration. It also increases the risk of premature birth, preeclampsia and blood clots, threatening the life of the mother and the fetus.
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Perhaps because nausea and vomiting are so common during pregnancy, hyperemesis doctors often look at hyperemesis, dismissing its serious symptoms as psychological, although it is the main reason for hospitalizations during early pregnancy, experts said. Although celebrities such as Kate Middleton and Amy Schumer have raised the profile of the condition in recent years by sharing their experiences, it remains understudied.
“I’ve been working on this for 20 years, and there are still reports of women dying because of this and women being mistreated,” said Dr. Marlena Fejzo, a geneticist at the University of Southern California Keck School of Medicine and a colleague. -author of the new study.
She knows firsthand the pain of the condition. During her second pregnancy, in 1999, Fejzo was unable to eat or drink without vomiting. She lost weight rapidly, becoming too weak to stand or walk. Her doctor was dismissive, suggesting that she was exaggerating her symptoms to get attention. She was eventually hospitalized and miscarried at 15 weeks.
Fejzo said she asked the National Institutes of Health to fund a genetic study of hyperemesis but was denied. Undeterred, she persuaded 23andMe, a popular genetic testing company, to include questions about hyperemesis in surveys of thousands of customers. In 2018, she published a paper showing that customers with hyperemesis tended to carry a gene variant for GDF15.
Hormones are chemicals that send messages throughout the body. GDF15 is released by many tissues in response to stress, such as infection. And its signal is very 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 Cambridge University in England measured the hormone in the blood of pregnant women and analyzed the genetic risk factors for hyperemesis.
The researchers found that women who had hyperemesis during pregnancy had significantly higher levels of GDF15 than women who had no symptoms.
But the effect of the hormone seems to depend on the sensitivity of the woman and the exposure to the hormone before pregnancy. The researchers found, for example, that women in Sri Lanka with a rare blood disorder that causes chronically high levels of GDF15 rarely experience nausea or vomiting during pregnancy.
“It wiped out all the nausea. They have very few symptoms when they are pregnant,” said Dr Stephen O’Rahilly, an endocrinologist at the University of Cambridge who led the research.
O’Rahilly suggested that prolonged exposure to GDF15 before pregnancy could have a protective effect, making women less sensitive to the sharp rise in hormones caused by the developing fetus.
In laboratory experiments, the scientists exposed some mice to a small amount of the hormone. When a much larger dose was given three days later, the mice did not lose their appetite as much as animals that had not been given the earlier dose – indicating a strong desensitization effect.
The findings offer hope for better treatments for hyperemesis, experts said. Patients with hyperemesis could one day take medications to block the effects of the hormone in the brain, if clinical trials found the drugs safe during pregnancy. Such medications are being tested in trials on cancer patients who also have loss of appetite and vomiting caused by GDF15.
It may even be possible to prevent the condition. Women at risk, such as those who have experienced severe nausea and vomiting during previous pregnancies, may be exposed to low doses of the hormone before becoming pregnant. (One diabetes drug, metformin, increases GDF15 levels and is already prescribed to help with fertility in some patients.)
The new study is powerful because it provides 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 be more widely recognized, she said.
“A lot of people have kind of assumed that women should be able to deal 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 someone’s head.”
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