Study uncovers the mechanism behind sickness and nausea that occur during pregnancy

A new study from authors including IGC’s Professor Caroline Hayward, and using data from the Generation Scotland cohort, uncovers that sensitivity to the protein GDF15 explains why many experience sickness and nausea whilst pregnant.

Nausea and vomiting affects as many as seven out of ten pregnancies. The most severe cases, known as Hyperemesis gravidarum (HG) having long-term health implications and often causing hospitalisation. A study published in the journal Nature has identified that sickness and nausea during pregnancy are caused by the presence of increased levels of a protein called GDF15, generated by the developing fetus, circulating in a pregnant person’s body. In addition, the levels of GDF15 in the body before pregnancy can affect whether sickness occurs when exposed to high levels of fetal GDF15 during pregnancy.

The study confirmed that high levels of GDF15 were likely responsible for pregnancy sickness and HG as GDF15 was present at higher levels in the blood of pregnant women who experienced vomiting than those who did not, and was at higher levels in pregnant women experiencing the most severe form of vomiting and nausea (HG) than those with milder symptoms.

Genetic variants associated with Hyperemesis gravidarum

The study team examined individuals carrying genetic variants of GDF15 to examine why some individuals may be more prone to sickness during pregnancy than others. They discovered that low levels of circulating GDF15 when not pregnant could contribute to an intolerance for the high levels of fetal GDF15 that occur during pregnancy and lead to HG and pregnancy sickness. Evidence from both a Croatian population cohort and the Generation Scotland cohort supported this conclusion.

This study provides valuable insights into the origin, regulation, and potentially causal role of GDF15 in pregnancy sickness and HG. Hopefully these findings will enable better treatment and management of pregnancy sickness and improve pregnancy experiences and outcomes

Croatian cohort

Researchers made use of data from the CROATIA-Korcula cohort to examine the levels of GDF15 in non-pregnant individuals carrying a single copy of GDF15 with a rare genetic variant (C211G) that had previously been shown to have an increased risk of developing HG.Circulating GDF15 was reduced by up to 50% in these individuals compared to controls, both supporting the link between GDF15 and HG, and showing that a single copy of this HG risk variant can cause lower GDF15 outwith pregnancy.

Generation Scotland

Researchers examined two additional genetic variants in and around the GDF15 gene, that have previously been associated with HG, in the Generation Scotland cohort and found that here too non-pregnant individuals carrying these variants showed lower levels of GDF15 than non-pregnant controls.

Beta Thalassaemia

If low levels of GDF15 outwith pregnancy can make it more likely that someone experiences HG or pregnancy sickness, then high levels of GDF15 outwith pregnancy may be preventative. This was confirmed by surveying people with Beta thalassemia, a condition that affects the amount of haemoglobin in red blood cells, who have constantly high levels of GDF15 even when not pregnant. The survey of these patients indicated that they experienced much reduced rates of nausea or vomiting when pregnant than a control group without the condition.

The importance of having cohort samples stored and kept for future use is exemplified by the identification of a rare variant, at comparatively high frequency, in the CROATIA-Korcula cohort and having the availability of serum samples for measurement of GDF15 in cases and matched controls.