Hormone surge reveals link between genetics and pregnancy sickness

A hormone produced by the fetus and placenta is directly related to nausea and vomiting experienced by many women during pregnancy.

An international team of scientists, from the University of Cambridge and scientists in Scotland, the USA and Sri Lanka, has shown that the degree of sickness experienced during pregnancy is caused by GDF15, a peptide hormone produced by the fetus and placenta. How sick a woman becomes is related to how much exposure she had to this hormone before becoming pregnant.

'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. We now know why.' Professor Sir Stephen O'Rahilly, director of the Medical Research Council Metabolic Diseases Unit at the University of Cambridge, who led the collaboration, said. '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.'

GDF15 is produced at low levels in all tissues outside of pregnancy. The team has shown that the amount of GDF15 in the blood prior to becoming pregnant is directly correlated to the severity of pregnancy sickness experienced. Women with low levels of GDF15 in their blood prior to pregnancy have a higher risk of developing severe nausea and vomiting.

Previous research has linked certain variants of the GDF15 gene to an increased risk of developing severe pregnancy sickness, known as hyperemesis gravidarum, which occurs in about one to three percent of pregnancies.

Publishing their results in Nature, the scientists analysed genetic data from more than 18,000 people; certain genetic variants of GDF15 led to the production of lower amounts of GDF15 in the blood and tissues, and were associated with a higher risk of developing hyperemesis gravidarum. In contrast, higher levels of GDF15 produced outside of pregnancy reduced the risk of hyperemesis gravidarum.

Conversely, women with beta-thalassaemia – a blood disorder caused by a mutation in a single gene that codes for haemoglobin – have normally very high levels of GDF15 in their blood prior to pregnancy and experience little or no nausea or vomiting.

Furthermore, mice exposed to a sudden high level of GDF15 lost their appetite, suggesting symptoms of nausea. In contrast, mice treated with GDF15 for three days prior to being exposed to a sudden high level of GDF15 did not lose their appetite.

Thus, the team suggest that by exposing women trying to conceive to GDF15 ahead of pregnancy could build up their resilience to the nauseating effect of the hormone and prevent pregnancy sickness. Alternatively, pregnancy sickness may be reduced by treatment with a drug to block GDF15 or its receptor.

Co-author Dr Marlena Fejzo from the Department of Population and Public Health Sciences at the University of Southern California whose team had previously identified the genetic association between GDF15 and hyperemesis gravidarum, said: 'Hopefully, now that we understand the cause of hyperemesis gravidarum, we're a step closer to developing effective treatments… '.