Scientists identify cause of severe morning sickness

The nausea and vomiting that often defines the first trimester of pregnancy are mainly caused 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 of it.

The study confirms previous research that pointed to the hormone GDF15. The researchers found that the amount of hormone circulating in a woman’s blood during pregnancy – as well as her exposure to it before pregnancy – determines 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 relentless vomiting and nausea throughout 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 fetus.

Perhaps because nausea and vomiting are so common during pregnancy, doctors often overlook hyperemesis and dismiss the serious symptoms as psychological, even though it is the leading cause of hospitalization in early pregnancy, experts say. Although celebrities such as Kate Middleton and Amy Schumer have brought attention to the condition in recent years by sharing their experiences, it remains under-exposed.

“I’ve been working on this for 20 years and yet there are still reports of women dying from this and women being abused,” said Dr. Marlena Fejzo, a geneticist at the University of Southern California’s Keck School of Medicine and co-researcher. author of the new study.

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

Dr. Fejzo said she asked the National Institutes of Health to fund a genetic study of hyperemesis but was turned down. 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 gene for GDF15.

Hormones are chemicals that send messages through the body. GDF15 is released by many tissues in response tension, such as an infection. And the signal is very specific: receptors for the hormone are clustered in a part of the brain responsible for nausea and vomiting.

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

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

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

“It completely wiped away all the nausea. They have virtually no symptoms during their pregnancy,” says Dr. Stephen O’Rahilly, an endocrinologist in Cambridge who led the study.

Dr. O’Rahilly hypothesized that long-term exposure to GDF15 before pregnancy could have a protective effect, making women less sensitive to the sharp rise in the hormone caused by the developing fetus.

In laboratory 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 appetite as much as animals that did not receive the earlier dose, demonstrating 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 show the medications are safe during pregnancy. Such drugs are being tested trials of cancer patients with loss of appetite and vomiting, also 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 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 in some patients to promote fertility.)

The new study is powerful because it provides genetic evidence of a causal link 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 more recognition, she said.

“Many people assume that women should just be able to deal with this,” said Doctor Freathy. With this biological explanation, she said, “there will be more belief that this is real, rather than something in someone’s head.”