We now know the cause of morning sickness

New research has identified the cause of the debilitating morning sickness experienced by most women during pregnancy – it’s largely a problem to do with the foetus.

Nausea and vomiting affect about 70% of pregnancies. Symptoms can be mild and temporary, or progress to a severe form known as hyperemesis gravidarum (HG). This occurs in up to 3% of pregnancies and can cause dehydration, nutrient deficiencies, and weight loss – putting both mother and foetus at risk.

The new research has found that the production of a hormone called GDF15 (hormone growth differentiation factor 15) by the foetus, and the pregnant person’s sensitivity to this hormone, is what causes nausea and vomiting.

The findings, which have been published in Nature, suggest that lowering GDF15 during pregnancy, or being pre-exposed to the hormone before pregnancy, may mitigate symptoms in some women.

Previous studies have linked GF15 sensitivity and morning sickness during pregnancy, however, this study is the first to describe the underlying mechanism causing this reaction.

“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,” says Dr Marlena Fejzo, clinical assistant professor of population and public health sciences at the University of Southern California, US, and the paper’s first author.

GDF15 is a hormone normally expressed in response to a range of cellular stresses. Its receptor is expressed in the hindbrain – the upper part of the spinal cord, brain stem, and cerebellum. When the receptor is activated by GDF15 this leads to nausea, vomiting, and aversive responses.

In this study, involving pregnant women in their first trimester, researchers identified a rare mutation in the gene that codes for GDF15 that leads to abnormally low levels of the hormone throughout the body.

They found that women with this mutation are at higher risk of developing HG during pregnancy, when they are suddenly exposed to more of the hormone than they are used to.

And, since increased levels of GDF15 during pregnancy originate almost entirely from the foetus, the mother may be less likely to develop HG if the foetus also inherits this mutation.

“For the first time, this interaction between mother and foetus helps explain why some women get HG during some – but not all – of their pregnancies,” Fejzo says.

The researchers also found that patients with beta thalassemia, an inherited blood disorder that causes chronically high levels of GDF15 already, are protected against HG and milder forms of pregnancy sickness.

Investigating the potential for treatments or preventative measures, they found that mice first exposed to a low “priming dose” of GDF15 did not show nausea-related appetite loss following a subsequent high dose of GDF15.

They also found evidence that lower GDF15 levels during a pregnancy can be safe, as babies were born normal and healthy in pregnancies where both the mother and foetus had the low-GDF15 mutation.

The researchers now hope to test whether priming women with exposure to GDF15 prior to pregnancy can reduce nausea and vomiting or prevent HG. They also aim to test a class of drugs that block GDF15 from binding to its receptor in the brain. 

“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,” adds Fejzo.

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