Late last year, geneticists found that the severe form of morning sickness, hyperemesis gravidarum (HG), is actually caused by the hormone GDF15, not human chorionic gonadotropin as previously believed. The researchers debunk common myths about morning sickness and propose potential treatments, such as desensitizing individuals to GDF15 before pregnancy, similar to how allergies are treated.
Late last year, geneticist Marlena Fejzo and colleagues made the discovery that morning sickness’s most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotrop.The author of a peer-reviewed opinion article in the journal Trends in Molecular Medicine, published on May 22, challenges common morning sickness misconceptions and explores potential treatments. According to the article, sensitizing individuals to GDF15 before pregnancy could be a viable approach, similar to the way allergies are treated. Fejzo, from the Keck School of Medicine of the University of Southern California, emphasizes the life-threatening nature of HG and the need to take adverse outcomes seriously. The article suggests that with the identification of GDF15 as the likely cause of HG, treatments targeting this hormone may soon be available.
The first myth to debunk is that severe morning sickness is harmless and normal. According to researcher Fejzo, pregnant individuals suffering from Hyperemesis Gravidarum (HG) are essentially starving, which has serious clinical implications for both the parent and child. Studies have shown that HG is a top predictor of postnatal depression, with 26% of those affected reporting suicidal thoughts and 18% meeting the criteria for post-traumatic stress disorder. Additionally, HG is associated with preterm birth, low birth weight, and long-term conditions such as autism spectrum disorder, ADHD, and depression.
Social issues, as well as an increased risk of childhood cancer and respiratory and cardiovascular disease, are associated with the condition. Despite this, pregnant individuals with HG are often not taken seriously by their doctors and families.
“It’s essentially a teratogen during pregnancy, a factor that disrupts normal fetal development, but many medical professionals still don’t take it seriously,” Fejzo explains. “Many people are dismissed and told, ‘oh that’s normal, it’s okay, just don’t take your prenatal vitamins; you don’t need them.'”
In severe cases, individuals with HG can develop Wernicke encephalopathy, a life-threatening swelling.In the brain, thiamine (vitamin B1) deficiency can lead to swelling due to hyperemesis gravidarum (HG). Because those with HG may struggle to take vitamins orally, the American College of Obstetricians and Gynecologists suggests replacing broad spectrum prenatal vitamins with folic acid, but Fejzo believes that this may not be enough and that thiamine supplementation should also be considered for individuals with HG. Fejzo emphasizes the importance of giving vitamin B1 to all women with hyperemesis to prevent serious brain swelling, which can result in permanent brain damage and fetal death.Morning sickness, often believed to be caused by human chorionic gonadotropic hormone (hCG), has recently been found to be primarily caused by the hormone GDF15, which is a part of the normal stress response. Typically, GDF15 is only expressed in small amounts, but during early pregnancy, it increases significantly, decreases, and then rises again during the third trimester. A study in Nature, co-authored by Fejzo, revealed that those who experience HG may have genetic variations that lead to lower levels of GDF15.GDF15 levels increase in women prior to pregnancy, making them more sensitive to high levels of GDF15 when they become pregnant. This discovery has important implications for preventing and treating HG, as initial research suggests that it could be safe to modify GDF15 during or even before pregnancy.
“It may be safe to modify GDF15 during or before pregnancy,” Fejzo explains. “If we can raise GDF15 levels before pregnancy, it could desensitize individuals, similar to how we desensitize people with severe allergies to allergens,” says Fejzo. “And during pregnancy, we might be able to manipulate GDF15 to mitigate the sensitivity.”
One way to reduce or eliminate symptoms is to prevent GDF15 or its receptors in the brain stem from being activated.”
Myth 3: Morning sickness is unique to humans
Nausea and loss of appetite during pregnancy is not exclusive to humans – these symptoms have been seen in various species, including monkeys, dogs, cats, chickens, vipers, and octopuses.
“I find it interesting that the recommendation for cats is to contact a veterinarian if they can’t eat for a day, but we don’t have that same recommendation for women with hyperemesis,” says Fejz.”If you tell your doctor’s office that you haven’t eaten for a day, they will likely consider it normal and not take any action. There seems to be more proactive care for cats than for humans.”
Fejzo also suggests that pregnancy-induced nausea may have evolved to prevent risky foraging trips, in addition to preventing the ingestion of harmful foods.
“It is likely that this condition evolved because it was advantageous to avoid searching for food during pregnancy,” Fejzo explains. “This may still be true for animals, but humans no longer need this, so let’s put an end to the suffering once and for all if possible.”
Currently, Fejzo is focused on developing a solution to help pregnant women who suffer from severe morning sickness.Ping and testing the suggested GDF15-based treatments. She also intends to explore other genes and GDF15 variants that may contribute to HG.
