A recent study from University of Cambridge explains why many pregnant women feel nauseous and vomit. The cause is a hormone produced by the baby called GDF15. The amount of this hormone and the mother’s prior exposure to it affect how sick she feels. The study suggests that exposing mothers to GDF15 before pregnancy could help prevent severe morning sickness.
Up to 70% of pregnancies experience nausea and vomiting. In about 1 to 3 out of 100 pregnancies, it can be severe, risking both the baby and the mother’s life, sometimes needing intravenous fluids to prevent dehydration.
This severe condition, called hyperemesis gravidarum, is the most common reason for pregnant women to be hospitalized in the first three months. Despite some available treatments, lack of awareness and fear of using medications during pregnancy often lead to insufficient care for women with this condition.
Until recently, the cause of pregnancy sickness was unknown. New evidence from studies on hormones and genetics suggests that the placenta’s production of GDF15 might be linked to nausea and vomiting.
An international study involving researchers from the University of Cambridge, Scotland, the USA, and Sri Lanka has made progress in understanding GDF15’s role in pregnancy sickness, including severe cases like hyperemesis gravidarum. The team used data from studies, including those at Rosie Maternity Hospital in Cambridge, employing human genetics, hormone measurement, and analyses in cells and mice.
The researchers discovered that the amount of nausea and vomiting during pregnancy is directly linked to how much GDF15 the placenta produces and releases into the woman’s bloodstream, as well as her sensitivity to the hormone’s nauseating effects.
GDF15 is produced at low levels in non-pregnant tissues. Her pre-pregnancy exposure to the hormone influences the mother’s sensitivity during pregnancy. Women with ordinarily low GDF15 levels have a higher risk of severe nausea and vomiting.
A rare genetic variant associated with a higher risk of severe morning sickness was linked to lower hormone levels in the blood and non-pregnant tissues. In contrast, women with the blood disorder beta thalassemia, naturally having high GDF15 levels before pregnancy, experience little to no nausea or vomiting.
Professor Sir Stephen O’Rahilly, 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 hospitalization. We now know why.”
Understanding this provides a clue on how to prevent it from happening. Blocking GDF15 from reaching its specific receptor in the mother’s brain could be the basis for an effective and safe treatment for this disorder.
In experiments with mice, those exposed to high GDF15 levels showed signs of nausea. However, those treated with a long-acting form of GDF15 did not exhibit similar behavior. The researchers suggest that increasing a woman’s tolerance to the hormone before pregnancy might be the key to preventing sickness.
Co-author Dr. Marlena Fejzo, who has personal experience with hyperemesis gravidarum, hopes that now, knowing the cause, effective treatments can be developed to spare other mothers from the challenging experiences she and many women have faced during pregnancy.
Charlotte Howden, previously healthy, experienced normal pregnancy until week six or seven when nausea began. Initially, she thought it was typical for early pregnancy. However, her condition worsened drastically a week later, leading to vomiting up to 30 times a day and an inability to keep food or fluids down, even water. Charlotte, later diagnosed with hyperemesis gravidarum (HG), couldn’t swallow saliva without getting sick, and excessive saliva production is a common HG symptom.
Recognizing this wasn’t normal, she sought help from her GP, but the advice given was limited to suggestions like trying ginger and adjusting daily activities, leaving her struggling with the severe symptoms of HG.
Upon returning to her GP, Charlotte was given a urine test for ketones, a chemical produced by the liver that can indicate a severe problem when levels are high. This was the only way she could be diagnosed with dehydration and referred for treatment. However, the test was challenging since she struggled to take fluids.
Charlotte noticed a disparity, as only women with HG were asked for this test, unlike other conditions where symptoms might be apparent. Despite not being referred, her GP prescribed the first-line medication for HG, which had limited effectiveness and made her excessively sleepy.
A second ketone test confirmed a problem, prompting immediate hospital admission. Charlotte describes her time in the early pregnancy ward as a traumatic experience.
In the hospital, Charlotte felt isolated among women experiencing pregnancy loss while she was still pregnant. People dismissed her severe morning sickness, comparing it to others facing miscarriages. After being rehydrated and discharged, she became sick again, leading to repeated hospital admissions and a mental toll. The cycle made her question the point of returning to the hospital, feeling completely broken.
Eventually, Charlotte reached a breaking point.
On her third hospital visit, Charlotte pleaded with the consultant for help, expressing thoughts of terminating the pregnancy. The consultant prescribed medication that made her feel incredible for 12 hours. However, when she needed a repeat prescription from her GP, they were unwilling to provide it, creating a disconnect between the GP and the consultant.
Charlotte, determined to fight, communicated with the consultant, who was surprised to learn about the medication refusal. The consultant intervened and ensured Charlotte received the necessary prescription. It took until around week 16 of her pregnancy to find the proper treatment for her sickness, and she continued taking the medication until week 37, fearful of stopping.
In 2016, Charlotte gave birth to a healthy son, Henry. Her challenging experience inspired her to advocate for other women. In 2020, she presented the world’s first documentary on hyperemesis gravidarum (HG) titled “Sick – The Battle Against HG.
Charlotte, now the Chief Executive of the charity Pregnancy Sickness Support, has joined a team of about 600 volunteers providing peer support and managing telephone helplines for those dealing with pregnancy sickness. She uses her role to raise awareness about the condition among women and healthcare professionals, advocating for including hyperemesis gravidarum (HG) in midwifery courses.
Charlotte is optimistic that the recent study may lead to effective treatments or even prevention for HG. She thanks Professor O’Rahilly and Dr. Fejzo for their work and for taking the condition seriously.
Reflecting on her own experience, she emphasizes the importance of researchers dedicating attention to conditions like HG, which often go unnoticed until high-profile cases bring them to public attention. She appreciates the dedication of researchers who have worked to understand and address a previously overlooked condition.
Journal reference:
- Fejzo, M., Rocha, N., Cimino, I. et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. DOI: 10.1038/s41586-023-06921-9.