Scientists pinpoint cause of morning sickness in new hope for a cure

Morning sickness is a common side-effect of pregnancy with eight out of 10 women being affected by nausea or vomiting, according to statistics from the UK’s National Health Service (NHS).

However, hyperemesis gravidarum (HG) is a condition when the morning sickness symptoms are so severe that the patient might need to be admitted to the hospital.

A team of international researchers led by the University of Cambridge have found that these symptoms could be linked to a hormone produced by the foetus – a protein known as GDF15.

This protein could be key in understanding why symptoms can range from unpleasant to endangering and could help find a way to prevent it.

A protein released into the mother’s blood

The severity of pregnancy-related nausea and vomiting is linked to the amount of GDF15 produced by the foetal placenta and released into the mother’s bloodstream.

“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 Professor Sir Stephen O’Rahilly who led the collaboration.

A woman’s sensitivity to this hormone contributes to the intensity of her symptoms.

The levels of GDF15 before pregnancy affect this sensitivity, with women having low pre-pregnancy GDF15 levels being at a higher risk of experiencing severe nausea and vomiting during pregnancy.

“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,” O’Rahilly added.

The work involved collaboration between scientists at the University of Cambridge, University of Southern California, University of Edinburgh, University of Glasgow and Kelaniya University in Colombo, Sri Lanka.

The team published their results in Nature.

‘A step closer to developing effective treatments’

The researchers believe that enhancing a woman’s tolerance to the hormone before pregnancy may be the key to preventing sickness.

Mice exposed to high, sudden levels of GDF15 displayed signs of appetite loss, indicating nausea. However, mice treated with a sustained-release version of GDF15 did not exhibit similar behaviour when exposed to acute hormone levels.

The researchers also discovered in a comparative study a rare genetic variation that significantly increases the susceptibility of women to HG. This variant was linked to reduced levels of the hormone in both the blood and non-pregnant tissues.

Likewise, women with the hereditary blood condition beta-thalassemia, characterised by naturally elevated GDF15 levels before pregnancy, tend to have minimal or no occurrences of nausea or vomiting.

The NHS estimates that between 1 and 3 per cent of pregnant women suffer from HG, with one well-publicised case being Catherine, the Princess of Wales, who experienced it during all three of her pregnancies.

Charlotte Howden is just one of the many women who have firsthand experience of how debilitating the condition can be.

She considered herself to be in good health before conceiving in her early thirties. Her pregnancy proceeded normally until around week six when she started experiencing nausea.

Initially, she dismissed it, attributing it to the typical discomfort of early pregnancy.

About a week later, Howden’s condition deteriorated significantly. She began vomiting up to 30 times a day, making it impossible to keep any food down.

“Every time I tried to eat something, which is obviously what I wanted to do, not only because I felt hungry, but because I was pregnant, that would then instantly make me sick,” she said in the statement.

To make matters worse, she couldn’t retain any fluids, not even water. Her condition, later identified as HG, became so severe that even swallowing saliva triggered vomiting necessitating several consultations with her GP and round trips to the hospital.

It wasn’t until approximately week 16 of her pregnancy that Charlotte found the appropriate treatment to alleviate her sickness. She remained on the prescribed medication until about week 37 because she was “terrified to discontinue it”.

She now works for the UK charity Pregnancy Sickness Support.

“When I was pregnant, I became so ill that I could barely move without being sick. When I tried to find out why, I realised how little was known about my condition, despite pregnancy nausea being very common,” said Dr Marlena Fejzo, a co-author of the study whose team had previously identified the genetic association between GDF15 and HG.

“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,” she added.