The Cause of Morning Sickness - Uncovered

In a recent study conducted by the University of Southern California and the University of Cambridge, researchers collaborated with medical professionals to investigate the causes of vomiting in pregnant women. During the study, researchers discovered the cause of morning sickness and nausea to be fluctuating levels of a certain hormone called GDF15. Researchers anticipate this breakthrough to bring new treatment options to patients. Here we'll discuss all you need to know about the GDF15 hormone and its impact on the treatment of pregnant women going forward.

GDF15, a protein produced by fetal cells in the placenta, plays a crucial role in pregnancy-related symptoms such as nausea, vomiting, and hyperemesis gravidarum (a severe, persistent form of vomiting during pregnancy). GDF15 is a hormone that surges during various bodily stressors such as infection or inflammation. The signals of this hormone are very specific as they are clustered in the part of the brain that trigger nausea. The hormone has been used as a marker in determining the severity of morning sickness. 

Figure 1. GDF15 clustered in area postrema in the brain which implies intracellular signaling causing morning sickness during pregnancy.

New research conducted at the University of Southern California and the University of Cambridge suggest  that women who have previously been exposed to the hormone at low levels prior to pregnancy experience more severe morning sickness and, in some cases, hyperemesis. Researchers believe there may be two plausible treatment plans for having high levels of GDF15 during pregnancy: (1) acclimating the brain to higher levels of GDF15 before pregnancy in order to desensitize the brain to high levels of the hormone or (2) reducing excessive levels of GDF15 entirely. 

Roughly 2% of women are hospitalized due to hyperemesis gravidarum which causes relentless nausea, vomiting, dehydration, weight loss, malnutrition, and drops in blood pressure. The disease has also caused an increased and prolonged risk of miscarriage, preterm birth and pre-eclampsia related blood clots which can be fatal to the fetus and the mother. 

Dr. Marlena Fejzo, a genetist at the University of Southern California highlights that because nausea and vomiting are such common symptoms of pregnancy, many primary care providers are dismissive often overlooking the diagnosis of hyperemesis gravidarum causing many women to miscarry early on in their first trimester. This motivated Dr. Fejzo to further study the effects of GDF15. Dr. Fejzo and her colleagues found that pregnant women who had hyperemesis had higher levels of GDF15 while they were pregnant compared to those with less morning sickness or no symptoms. The researchers also discovered that women who have chronically high levels of GDF15 prior to pregnancy rarely experienced nausea or vomiting during pregnancy. This suggests that long term exposure to the GDF15 hormone before pregnancy can serve as a protective measure against morning sickness and hyperemesis.

 Following the study, scientists tested the hypothesis by exposing mice to higher doses of the GDF15 hormone to evaluate its potential as a preventative or protective treatment. The trial established that after increasing hormone dosage, the mice did not lose their appetites, hence supporting their hypothesis that pre-exposure to the GDF15 hormone is be a protective measure to developing morning sickness.

Takeaways:

GDF15’s association with vomiting during pregnancy could explain why some women are more prone to developing morning sickness and hyperemesis than others. This discovery could lead to the development of preventative treatment options for vomiting in pregnancy which could greatly improve outcomes for patients around the world. 

Written by Sarosh Momin.

Edited by Nikhita Joshi.

References

1. Ghorayshi A. Scientists Pinpoint Cause of Severe Morning Sickness. The New York Times. https://www.nytimes.com/2023/12/13/health/morning-sickness-hyperemesis-gravidarum.html.   Published December 13, 2023.
2. Moniuszko S, Kraus T. Scientists may have pinpointed morning sickness cause, sparking hope for potential cures - CBS News. www.cbsnews.com. Published December 15, 2023. Accessed April 28, 2024. https://www.cbsnews.com/news/morning-sickness-cause-pregnancy-hormone-treatment/ 
3. Abrams Z. Researchers identify gene mutations linked to pregnancy sickness. Newsroom. Published March 15, 2022. Accessed April 28, 2024. https://keck.usc.edu/news/researchers-identify-gene-mutations-linked-to-pregnancy-sickness/ 
4. Fejzo M, Rocha N, Cimino I, et al. GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. Published online December 13, 2023:1-3. doi:https://doi.org/10.1038/s41586-023-06921-9 
5. Klien G. The OB/GYN-Guide: Insights with Dr. Klein: Understanding the New Breakthrough in Morning Sickness Treatment: The Role of GDF15. The OB/GYN-Guide. Published December 14, 2023. Accessed April 28, 2024. https://geffreyklein.blogspot.com/2023/12/understanding-new-breakthrough-in.html 
6. Lockhart SM, Saudek V, O’Rahilly S. GDF15: A Hormone Conveying Somatic Distress to the Brain. Endocrine Reviews. 2020;41(4). doi:https://doi.org/10.1210/endrev/bnaa007