Irish professor leads team in finding potential cure for pregnancy sickness

A team of scientists led by Ireland's Prof Stephen O'Rahilly say they have discovered why some women become extremely sick during pregnancy, which could lead to a possible cure.

A collaborative study led by Professor O’Rahilly, has shown why many women experience nausea and vomiting during pregnancy – and why some women become so sick they need to be admitted to hospital.

As many as seven in ten pregnancies are affected by nausea and vomiting. In some women – thought to be between one and three in 100 pregnancies – it can be severe, even threatening the life of the fetus and the mother and requiring intravenous fluid replacement to prevent dangerous levels of dehydration. So-called hyperemesis gravidarum is the commonest cause of admission to hospital of women in the first three months of pregnancy.

Although some therapies exist to treat pregnancy sickness and are at least partially effective, widespread ignorance of the disorder compounded by fear of using medication in pregnancy mean that many women with this condition are inadequately treated, Cambridge University outlines. 

Until recently, the cause of pregnancy sickness was entirely unknown, but evidence from biochemical and genetic studies has suggested that it might relate to the production by the placenta of the hormone GDF15, which acts on the mother’s brain to cause her to feel nauseous and vomit.

Now, this international study, involving scientists at the University of Cambridge and researchers in Scotland, the USA and Sri Lanka, has made a major advance in understanding the role of GDF15 in pregnancy sickness, including hyperemesis gravidarum.

The researchers studied data from women recruited to a number of studies, including at the Rosie Maternity Hospital, part of Cambridge University Hospitals NHS Foundation Trust and Peterborough City Hospital, North West Anglia NHS Foundation Trust. They used a combination of approaches including human genetics, new ways of measuring hormones in pregnant women’s blood, and studies in cells and mice.

They showed that the degree of nausea and vomiting that a woman experiences in pregnancy is directly related to both the amount of GDF15 made by the fetal part of placenta and sent into her bloodstream, and how sensitive she is to the nauseating effect of this hormone.

GDF15 is made at low levels in all tissues outside of pregnancy. How sensitive the mother is to the hormone during pregnancy is influenced by how much of it she was exposed to prior to pregnancy – women with normally low levels of GDF15 in blood have a higher risk of developing severe nausea and vomiting in pregnancy.

The team found that a rare genetic variant that puts women at a much greater risk of hyperemesis gravidarum are associated with lower levels of the hormone in the blood and tissues outside of pregnancy. Similarly, women with the inherited blood disorder beta thalassemia, which causes them to have naturally very high levels of GDF15 prior to pregnancy, experience little or no nausea or vomiting.

"Most women who become pregnant will experience nausea and sickness at some point, and while this is not pleasant, for some women it can be much worse – they’ll become so sick they require treatment and even hospitalisation," Prof O'Rahilly said

"We now know why – 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. It also makes us more confident that 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," Prof O'Rahilly said.

Nausea and vomiting in pregnancy linked to hormone from fetus https://t.co/TI7psoCsAr

Thanks to Alice and Rachel for this very nice News and Views !

— stephen o'rahilly (its pronounced O-RA-hill-EEE) (@StephenORahilly) December 13, 2023

A native of Dublin, Prof O'Rahilly studied medicine at University College Dublin, graduating in 1981.  

See the video produced by University of Cambridge below to learn more.