A new study conducted by the University of Southern California (USC) and the University of Cambridge has identified a key cause of pregnancy sickness, offering the possibility of prevention. The research, published in the journal Nature, reveals that a hormone produced by the fetus, called GDF15, and a mother’s sensitivity to this hormone are responsible for causing nausea and vomiting during pregnancy. The study suggests that pre-pregnancy exposure to GDF15 may help alleviate symptoms in some women.
Nausea and vomiting are common symptoms experienced by expectant mothers, affecting around 80% of women during pregnancy. However, approximately 2% of women suffer from a severe form of pregnancy sickness called hyperemesis gravidarum (HG), which can result in weight loss, dehydration, and hospitalization. Until now, the cause of these symptoms has been largely unknown. However, the study’s findings indicate that GDF15 is a causal factor in pregnancy sickness and that a woman’s sensitivity to the hormone determines the severity of her symptoms. Women exposed to lower levels of GDF15 before pregnancy tend to experience more severe symptoms.
Dr. Marlena Fejzo, the first author of the paper and a clinical assistant professor at the Keck School of Medicine, explains, We now know that women get sick during pregnancy when they are exposed to higher levels of the hormone GDF15 than they are used to. Furthermore, Professor Sir Stephen O’Rahilly, the co-director of the Wellcome-Medical Research Council Institute of Metabolic Science at the University of Cambridge, suggests that understanding a woman’s sensitivity to GDF15 provides a clue for potential prevention methods.
Lowering GDF15 levels might be one possible approach to address pregnancy sickness. The study also indicates that exposing women to GDF15 before pregnancy, to prepare them for elevated hormone levels during pregnancy, could help reduce symptoms. Dr. Fejzo states, This study provides strong evidence that one or both of those methods will be effective in preventing or treating HG.
The researchers used various methods to establish the link between GDF15 and pregnancy sickness, including genetic analyses, blood tests, and studies on human cells and mice. They discovered that a rare mutation in the gene responsible for producing GDF15 results in abnormally low hormone levels, putting women at a higher risk of developing HG when exposed to sudden increases during pregnancy. Additionally, patients with beta thalassemia, a genetic blood disorder causing high GDF15 levels, were found to be mostly protected against HG.
To investigate the potential for preventive measures, the research team exposed mice to GDF15 before pregnancy. Mice given a high dose of GDF15, simulating pregnancy levels, showed signs of appetite loss, indicating nausea. However, mice administered a low priming dose of GDF15 did not exhibit the same appetite loss when given the high dose afterward.
The study’s human evidence also indicates that maintaining lower GDF15 levels during pregnancy could be safe. Pregnancies in which both the mother and fetus possessed the low-GDF15 mutation resulted in normal, healthy births, suggesting that reducing GDF15 levels throughout pregnancy might be another safe way to prevent HG.
The next step for the research team is to investigate whether priming women with GDF15 exposure prior to pregnancy can reduce nausea and vomiting or even prevent HG. Dr. Fejzo is currently seeking funding to test the safety and effectiveness of metformin, a drug that increases GDF15 levels, in patients with a history of HG. The researchers also plan to explore drugs that block GDF15 from binding to its receptor in the brain, which could potentially help with HG symptoms. Some of these drugs are already undergoing clinical trials for cachexia and nausea and vomiting in cancer patients.
The study’s findings offer hope for women who have experienced severe illness during pregnancy, including Dr. Fejzo herself. She states, Hopefully, now that we understand the main cause of HG, we’re a step closer to developing effective treatments to stop other mothers from going through what I, and many other women, have experienced.
The research was primarily funded by the UK Medical Research Council and the National Institute for Health and Care Research, with additional funding from various sources.
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