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Cause of Morning Sickness and a Potential Treatment Identified

A pregnant woman covering her mouth with her hand.
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As many as 70-80% of women are affected by nausea and vomiting during pregnancy, with 1-3% of cases requiring life-saving medical interventions. Researchers from the University of Cambridge have finally uncovered an underlying cause of pregnancy sickness in a new study published in Nature.

What makes morning sickness so serious?

Pregnancy sickness, also referred to as morning sickness, can be life-threatening to both mother and fetus. In some cases, mothers may require intravenous fluid replacement to prevent dangerous levels of dehydration. Severe sickness – called hyperemesis gravidarum (HG) – is the most common cause of hospital admission during the first three months of pregnancy.

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While there are some treatments available for pregnancy sickness, they frequently exhibit limited effectiveness. Coupled with widespread fear since the tragedy of thalidomide, women suffering from this condition are often ignored and insufficiently treated.

The cause of morning sickness was entirely unknown until very recently. Biochemical and genetic studies have suggested the hormone GDF15 might play a role, however there has been a lack of mechanistic research into these genome associations.

The role of GDF15

The research team, led by Professor Sir Stephen O’Rahilly, co-director of the Wellcome-Medical Research Council Institute of Metabolic Science at the University of Cambridge, used data from women that had been recruited for several studies across hospital sites in the UK. Using a combination of approaches, including a novel method for measuring hormones in pregnant women’s blood, the researchers investigated levels of GDF15 in humans in addition to cell cultures and mice.

GDF15 is produced at low levels in all human tissues when an individual is not pregnant, however during gestation it is produced by the placenta at much higher levels. O’Rahilly and colleagues found that the degree of sickness a pregnant woman experiences, and her risk of developing HG, is directly related to her sensitivity to the effects of GDF15 and the levels of GDF15 in the bloodstream during pregnancy.

Women who had naturally low levels of GDF15 in their blood prior to pregnancy, were at a higher risk of HG during pregnancy compared to those who did not. O’Rahilly and colleagues also found that a rare genetic variant, which puts women at a much greater risk of HG, was associated with lower levels of the hormone in the blood and tissues outside of pregnancy. In addition, women with the inherited blood disorder beta thalassemia, which causes them to have naturally very high levels of GDF15 before pregnancy, experience little or no nausea or vomiting.


“The baby growing in the womb is producing a hormone at levels the mother is not used to. The more sensitive she is to this hormone, the sicker she will become. Knowing this gives us a clue as to how we might prevent this from happening,” said O’Rahilly.

Finding an effective treatment for pregnancy sickness

Mice that were exposed to acute, high levels of GDF15 showed signs of a loss of appetite, suggesting that they were experiencing nausea, however those that were treated with a long-acting form of GDF15 did not show similar behavior when exposed to acute levels of the hormone. These results suggest that building up a woman’s tolerance to the hormone prior to pregnancy could hold the key to preventing sickness.


“Preventing GDF15 from accessing its highly specific receptor in the mother’s brain will ultimately form the basis for an effective and safe way of treating this disorder,” said O’Rahilly.


Co-author Dr. Marlena Fejzo from the Department of Population and Public Health Sciences at the University of Southern California said: “Hopefully, now that we understand the cause of hyperemesis gravidarum, we’re a step closer to developing effective treatments to stop other mothers going through what I and many other women have experienced.”


Reference: Fejzo M, Rocha N, Cimino I, et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. 2023. doi: 10.1038/s41586-023-06921-9

This article is a rework of a press release issued by the University of Cambridge. Material has been edited for length and content.