Scientists have discovered a hormone that causes nausea and vomiting during pregnancy, pointing the way toward future treatment options.
When geneticist Marlena Fejzo was pregnant for the first time, she suffered from nausea and vomiting like a majority — approximately 70% — of pregnant people do. In most cases, symptoms are manageable and often dissipate by the end of the first trimester. However, Fejzo’s illness was severe. She lost 15 pounds and went to the emergency room twice but was never officially given a diagnosis of hyperemesis gravidarum: a severe type of nausea and vomiting during pregnancy.
There is no scientific consensus as to what qualifies a person’s nausea and vomiting as “severe,” and estimates of the number of pregnant people affected by it range from 0.3% to 10.8%, according to research published in the journal Frontiers in Medicine.
It is a “diagnosis of exclusion,” Dr. Emmanuelle Bagdasarian, an OB-GYN on staff at Good Samaritan Medical Center in Palm Beach, Florida, told HuffPost. “Hyperemesis is when there is constant, unrelenting vomiting with weight loss and intolerance to oral fluids and food, with no other causes that are identifiable,” she said.
The condition, which is the leading cause of hospitalization in early pregnancy, can cause unimaginable suffering. Both the Duchess of Cambridge and comedian Amy Schumer were hospitalized with it during their pregnancies, and historical records indicate that British author Charlotte Brontë’s 1855 death can be attributed to the disease.
After giving birth to her first child, Fejzo became pregnant a second time.
“I didn’t even think it could be worse, but it was much, much worse,” she told HuffPost. “I couldn’t eat, drink or move without violently vomiting. So it really was torture for weeks. I just had to lay completely still in bed without moving.”
She was treated with intravenous fluids, as is standard for dehydration, as well as a feeding tube and seven drugs — none of which provided relief. Her symptoms continued until she lost the pregnancy at 15 weeks.
Because she was receiving IV fluids but was completely bedridden, she required regular bedpan changes and other care throughout the day. One of the most shocking parts of the ordeal, though, was gaslighting from the medical establishment.
She recalled being told she was just seeking attention from her husband and family, “Like I really enjoyed having my father change my bedpan.”
As Fejzo discovered, while pregnant people have suffered from nausea and vomiting for all of human history, much of that history includes a male-dominated medical profession dismissing their suffering.
For decades, researchers have practically ignored hyperemesis gravidarum. But after her experience, Fejzo set out to change that. She knew there was a biological cause to her illness.
In 2018, Fejzo, who holds a doctorate in genetics, and her colleagues published a paper showing that two genes, GDF15 and IGFBP7, are involved in hyperemesis gravidarum. Finally, here was scientific evidence that the condition is not psychological.
Last week, Fejzo and her co-authors published another paper, which explains the mechanism by which the hormone produced by the GDF15 gene (also called GDF15) causes nausea and vomiting.
While this discovery illuminates a potential path to more effective treatments, there’s more to learn about the relationship between GDF15 and nausea and vomiting. For now, though, here’s what you need to know.
What is GDF15?
Both the gene and the hormone it produces are called GDF15. Fejzo explained that we can think of our genes as “recipes,” and the GDF15 gene provides the instructions to make the GDF15 hormone. This hormone is produced by what Fejzo called “the fetal part of the placenta.” But pregnancy is not the only time a person has the hormone in their body. For instance, cancer patients dealing with cachexia, a syndrome that causes weight loss, loss of appetite and more, is caused by rising levels of the GDF15 hormone.
“Unhealthy tissues make it, so, whenever you’re sick, like if you have a viral or bacterial infection,” she said. “It goes up when you have kidney damage or liver damage. Any time any organ in your body or any cells in your body are under some kind of physical stress, they are going to produce this hormone.”
The theory is that humans evolved this gene to prevent them from feeling hunger and going out to hunt for food when their bodies were in a weakened state, as they were more likely to be taken down by a predator while ill.
It’s important to note that GDF15 and human chorionic gonadotropin are two different hormones. HCG is the hormone that’s detected by pregnancy tests because it’s a hormone produced only in pregnancy. If you are a fertility patient, you may have your levels of this hormone tested throughout early pregnancy, as falling HCG levels can predict miscarriage. But there isn’t evidence that HCG causes nausea and vomiting.
How does GDF15 cause hyperemesis gravidarum?
What Fejzo and her colleagues discovered is that people who have lower pre-pregnancy levels of the GDF15 hormone are more likely to experience nausea and vomiting. This is due to mutations on their GDF15 gene. It is as though their tolerance for GDF15 is low, and when the placenta produces more of it during pregnancy they are more likely to have symptoms.
“Everybody has GDF15 in their pregnancy, it’s produced by the fetal part of the placenta. But people that have this predisposition for lower levels before they get pregnant are going to be hypersensitive to it,” Fejzo said.
Researchers also found that people with hyperemesis gravidarum had higher levels of GDF15.
Those most likely to suffer severe symptoms, like the ones Fejzo endured, are people who “have this predisposition for lower levels prior to pregnancy,” she said.
What are some ways we may be able to treat hyperemesis gravidarum in the future?
One possible treatment could involve building up a tolerance for GDF15 prior to pregnancy in people who are genetically predisposed to hyperemesis gravidarum, similar to how allergy shots build up a tolerance to allergens. Trials using this strategy on mice have been successful, Fejzo said.
Fejzo and her co-authors also surveyed women with a genetic condition called beta thalessimia, which leads to higher levels of GDF15. They found that these women were much less likely to have nausea and vomiting during their pregnancies, with only around 5% reporting these symptoms. This is further evidence that a high tolerance is protective.
There are also drugs to treat cancer cachexia, a wasting syndrome, currently in clinical trials, and these may be effective for hyperemesis gravidarum patients.
What can I do if I am sick right now?
If you are pregnant and suffering from nausea and vomiting, it’s important to understand that your illness is real, Fajzo said. Find a health care provider who will listen to you and take your symptoms seriously. The HER Foundation, for which Fejzo serves as a board member and research adviser, can help you locate a provider and volunteers who can offer you support.
If you are unable to eat and drink normally, are losing weight or becoming dehydrated, it’s important to seek medical attention. You may need IV fluids. In addition to that, you may need to take a vitamin called thiamine (vitamin B1). Lack of this vitamin can lead to a serious neuropsychiatric condition known as Wernicke encephalopathy, but this is completely preventable in hyperemesis gravidarum patients. If you cannot take vitamin pills due to vomiting, thiamine can be administered intravenously.
Bagdasarian said there are several levels of treatments, starting with ginger and avoiding hard-to-digest fatty foods. A next step would be vitamin B6 and doxylamine (also known as Unisom, a sleep aid).
“If this is not working, then we move on to anti-emetic medications,” such as Zofran and reglan. “The treatments are effective,” she said, but noted that “the goal is to control symptoms. A lot of times, completely treating the condition
is not realistic.”
Bagdasarian also said that hyperemesis gravidarum “usually does not have any fetal adverse events. Lower birth weight is common, but usually that is the only complication.”
However, you should not delay getting care. According to Bagdasarian, hyperemesis can be a sign that you are carrying more than one fetus or have other complications.
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