Hormones From Fetus May Cause Morning Sickness, Says Study

New research revealed insights into how hormones produced by the developing embryo play a role in morning sickness and its severity.

Morning sickness is perhaps one of the most unexplained aspects of pregnancy despite the fact that about 90% of pregnant women experience it to some degree. Though the level of nausea and vomiting of morning sickness can vary, up to 3% of pregnant women develop severe vomiting, known as hyperemesis gravidarum (HG). This condition can lead to dehydration and hospitalization.

Despite the high prevalence of morning sickness among pregnant individuals, few treatments exist to help quell the symptoms. However, researchers recently found that combining doxylamine-pyridoxine and acupuncture may help.

While no one knows for sure what causes morning sickness or HG, a 2018 study found a link between the hormone growth differentiation factor 15 (GDF15) and nausea and vomiting during pregnancy. GDF15 acts on the part of the brainstem that controls vomiting, and its overproduction has been associated with nausea in individuals with cancer.

In a new study published on December 13 in Nature, a multi-national team of researchers revealed that an individual's sensitivity to GDF15 — a hormone produced by the fetus — may determine whether they experience morning sickness during pregnancy.

What causes morning sickness?

To investigate GDF15's role in pregnancy-related nausea, vomiting, and hyperemesis gravidarum, scientists conducted genetic and blood test analyses on pregnant women with and without HG.

The researchers discovered that the participants' GDF15 levels rose steadily in the first 12 weeks of pregnancy but were higher on average in those who experienced morning sickness and hyperemesis gravidarum. They also found that lower GDF15 levels in the mother before pregnancy were linked with a higher risk of developing HG.

In addition, the research team developed a mass-spectrometry-based method to measure how much GDF15 circulating in the mother's blood came from the fetus. The team discovered that most of the circulating GDF15 in pregnancy came from the developing embryo.

Moreover, the study's authors say women with β-thalassaemia — a condition characterized by chronically high GDF15 levels — rarely reported morning sickness during pregnancy.

The research team suspects that individuals with naturally low levels of GDF15 might be more sensitive to increased levels of the fetal hormone during pregnancy and, thus, may be more likely to experience morning sickness than those with naturally high levels of the hormone.

When the team conducted mouse experiments to investigate further, they found that rodents exposed to a high dose of GDF15 lost their appetite, which is a characteristic of nausea. However, mice exposed to a low dose of the hormone before receiving a high dose did not exhibit appetite loss.

Moreover, the study’s authors suggest that a rare mutation in the gene that codes for GDF15 may determine whether a pregnant woman develops morning sickness. And this helps explain why the level of morning sickness in one pregnancy can be so different from the next.

Lead study author Marlena Fejzo, Ph.D., a clinical assistant professor of population and public health sciences in the Center for Genetic Epidemiology at the Keck School of Medicine, tells Healthnews, "This new Nature study offers the first explanation for why one pregnancy can be so different from the next because it shows that the level of nausea and vomiting is determined by a combination of the mother's sensitivity to the hormone GDF15 as well as the level of the hormone produced by the fetus."

Fejzo, who has experienced HG during pregnancy, says the study had cases where the mothers possessed a GDF15 lowering mutation that made them ten times more likely to get HG.

"But sometimes when that mutation is passed on to the baby, the mother will not get HG because even though the mother is hypersensitive to the hormone, the part of the placenta carrying the baby's genes is producing abnormally low levels of it," Fejzo explains.

Is a cure for morning sickness in sight?

In light of this discovery, the research team plans to examine whether exposing women to low levels of GDF15 before pregnancy can reduce the risk of morning sickness and HG. In addition, Fejzo is now applying for funding to investigate metformin, a drug that increases GDF15 levels, to see if it's safe for use in people with a history of HG. They also want to examine whether other medications, such as GDF15 blockers, could safely and effectively lower the risk of pregnancy-related nausea and vomiting.

Until results of these investigations become available, Fejzo recommends that pregnant individuals concerned about hyperemesis gravidarum should consider visiting the Hyperemesis Education & Research (HER) Foundation website for information and support.