Cambridge-led study discovers cause of pregnancy sickness – and potential treatment

Published: 18 December 2023

A new study supported by NIHR Cambridge Biomedical Research Centre (BRC) 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.

Pregnancy sickness

Nausea and vomiting in pregnancy is very common in early pregnancy and can affect day-to-day life. For some women the sickness can be severe, threatening the life of the foetus and the mother. This is called hyperemesis gravidarum. Women affected may need to be treated with anti-sickness medication. Sometimes they require intravenous fluid in hospital to prevent dehydration. Lack of understanding of the disorder and fear of using medication in pregnancy means that many women with this condition are inadequately treated.

Recent studies suggested that pregnancy sickness is related to the production of the hormone GDF15 by the placenta. This acts on the mother’s brain to cause her to feel nauseous and vomit.

International study

The work involved collaboration between scientists from:

• the University of Cambridge
• the University of Southern California
• the University of Edinburgh
• the University of Glasgow
• the University of Kelaniya in Colombo, Sri Lanka

The researchers used human genetics and new ways of measuring hormones in pregnant women’s blood.

They found that how sick the mother feels depends on: 

• how much of the hormone is produced by the foetus
• how much exposure the mother had to this hormone before becoming pregnant 

The researchers found that women with low levels of the hormone in their blood before pregnancy have a higher risk of developing severe nausea and vomiting in pregnancy. A rare genetic variant that puts women at a much greater risk of hyperemesis gravidarum was associated with lower levels of the hormone in the blood and tissues outside pregnancy. 

Women with high levels of the hormone prior to pregnancy because of an inherited blood disorder experience little or no nausea or vomiting.

Potential way to prevent pregnancy sickness

The research has been published in Nature. It suggests a potential way to prevent pregnancy sickness, by exposing mothers to the hormone ahead of pregnancy to build up their resilience.  

Professor Sir Stephen O’Rahilly, Scientific Director at the NIHR Cambridge Biomedical Research Centre, and Co-Director of the Institute of Metabolic Science and Director of the Medical Research Council Metabolic Diseases Unit at the University of Cambridge, who led the collaboration, said: “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.

“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.”

Made possible by NIHR research infrastructure

The experiments underpinning the study relied heavily on NIHR Cambridge BRC research infrastructure. They drew on:

• NIHR Cambridge Bioresource (for validation of GDF15 assays on participants recruited by genotype)
• Cambridge NIHR BRC Core Biochemical Assay Laboratory (CBAL), where all the immunoassays were evaluated and executed
• BRC support for Richard Kay, who did the crucial peptidomics
• the Cambridge Baby Growth Study (part of the BRC’s Antenatal, Maternal and Child Health theme) 
• the Pregnancy Outcome Prediction study (POPs) 
• HG vs control sample collection from the BRC’s Nutrition, Obesity, Metabolism and Endocrinology theme

Professor O’Rahilly said: “The support of the NIHR Cambridge Biomedical Research Centre has been critical for the success of this study. The BRC has provided crucial support to our Peptidomics lab to help with our analysis and access to resources like the BRC supported Clinical Biochemistry Assay Lab has been essential to deliver this significant breakthrough in understanding hyperemesis gravidarum. 

“The BRC provides us with an opportunity to collaborate with expertise from University of Cambridge, Cambridge University Hospitals and other research themes like Professor Gordon Smith, whose samples from his Pregnancy Outcome Prediction Study was vital in our discovery. Without the necessary infrastructure and resources the BRC provides, this study would not have been made possible.”

Professor Miles Parkes, NIHR Cambridge BRC director said: “It’s great to see this great breakthrough coming out of the O’Rahilly group. It represents a major step towards better treatment of hyperemesis gravidarum – the most severe and dangerous form of nausea and vomiting in pregnancy that often leads to mums spending long periods in hospital. This work has been supported at each step by the research infrastructure of the NIHR Cambridge Biomedical Research Centre. It emphasises the importance of this NHS-funded infrastructure in delivering major biomedical discoveries of potentially transformational significance with regards to improved health of patients in Cambridge and around the world.”

Read the study in Nature.