Scientists identify cause of severe morning sickness

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The nausea and vomiting that often define the first trimester of pregnancy are caused primarily by a single hormone, 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 had pointed to the hormone called GDF15. Researchers found that the amount of the hormone circulating in a woman's blood during pregnancy, as well as her exposure to it before pregnancy, influences the severity of her symptoms.

More than two-thirds of pregnant women experience nausea and vomiting during the first trimester. And about 2 percent of women are hospitalized for a condition called hyperemesis gravidarum, which causes incessant vomiting and nausea throughout pregnancy. The condition can cause malnutrition, weight loss and dehydration. It also increases the risk of premature birth, preeclampsia and blood clots, endangering the lives of the mother and fetus.

Perhaps because nausea and vomiting are so common during pregnancy, doctors often overlook hyperemesis and dismiss its serious symptoms as psychological, even though it is the leading cause of hospitalization during early pregnancy, they said. The experts. Although celebrities such as Kate Middleton and Amy Schumer have raised the profile of the disease in recent years by sharing their experiences, it remains understudied.

“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 Keck University School of Medicine. of Southern California and co-author of the new study.

She knows firsthand the pain of this condition. During her second pregnancy, in 1999, Dr. Fejzo could not eat or drink without vomiting. She quickly lost weight and became too weak to stand or walk. Her doctor was dismissive and she suggested that she was exaggerating her symptoms to get attention. She was eventually hospitalized and miscarried at 15 weeks.

Dr. Fejzo said she asked the National Institutes of Health to fund a genetic study of hyperemesis, but was rejected. Undeterred, she convinced 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 clients with hyperemesis tended to carry a variant in a GDF15 gene.

Hormones are chemicals that send messages throughout the body. Many tissues release GDF15 in response to stress, such as infection. And its signal is very specific: the hormone receptors are clustered in a part of the brain responsible for nausea and vomiting.

In the new study, Dr. Fejzo and his collaborators at the University of Cambridge in England measured the hormone in the blood of pregnant women and analyzed genetic risk factors for hyperemesis.

The researchers found that women who experienced hyperemesis had significantly higher GDF15 levels during pregnancy than those who had no symptoms.

But the hormone's effect appears to depend on the woman's sensitivity and exposure to the hormone before pregnancy. Researchers found, for example, that women in Sri Lanka with a rare blood disorder that caused chronically high levels of GDF15 rarely experienced nausea or vomiting during pregnancy.

“It completely eliminated all the nausea. They have virtually no symptoms during pregnancy,” said Dr. Stephen O'Rahilly, a Cambridge endocrinologist who led the research.

Dr. O'Rahilly hypothesized 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 laboratory experiments, scientists exposed some mice to a small amount of the hormone. When given a much higher dose three days later, the mice did not lose their appetite as much as animals that did not receive the previous dose, showing a strong desensitization effect.

The findings offer hope for better treatments for hyperemesis, experts said. Patients with hyperemesis could someday take medications to block the hormone's effects on the brain, if clinical trials find the drugs safe during pregnancy. These drugs are being tested in trials with cancer patients with 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, 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 fertility in some patients.)

The new study is powerful because it provides genetic evidence for a causal relationship between GDF15 and the disease, said Dr. 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.

“Many people assume that women should be able to cope with this,” Dr. Freathy said. With this biological explanation, he said, “there will be more beliefs that this is something real than something that is in someone's head.”



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