Is Morning Sickness Actually Preventable?

Morning sickness, or as researchers more accurately call it, nausea and vomiting of pregnancy (NVP), affects about 70% of pregnant individuals, typically during the first trimester. While it’s colloquially referred to as "morning sickness," the nausea can strike at any time of day. For some, the experience can be severe, leading to a condition known as hyperemesis gravidarum (HG), which impacts a smaller percentage of pregnant people but can require hospitalization and IV fluids.

#### The Search for Causes

For years, scientists have explored the biological mechanisms behind NVP and HG. Early hypotheses suggested that heightened sensitivity to smells and tastes could help pregnant individuals avoid spoiled food, thereby protecting both them and their developing fetus. However, the quest for a definitive cause led researchers to consider hormonal influences.

Initially, it was believed that elevated levels of human chorionic gonadotropin (hCG) might be responsible for NVP. Yet, recent data has cast doubt on this theory, as conclusive evidence linking hCG to nausea was lacking. Instead, attention has shifted to a different hormone: **Growth Differentiation Factor 15 (GDF15)**.

#### What is GDF15?

GDF15 is a stress-response hormone that everyone possesses, and its levels can increase in various situations, such as exposure to toxins. Its primary function appears to be signaling the body to induce vomiting when necessary, making it a key player in the nausea experienced during pregnancy. Research from 2018 identified a genetic component to GDF15 levels, and subsequent studies have linked certain mutations in the GDF15 gene to more severe cases of HG.

#### Genetic Factors and Nausea Sensitivity

Recent findings indicate that the relationship between GDF15 and NVP might be more complex than previously thought. A 2023 study proposed that some individuals have a low baseline level of GDF15. Upon becoming pregnant, the placenta and fetus produce large amounts of GDF15, causing a spike that can lead to severe nausea.

But why would a developing fetus release a hormone that makes the pregnant person feel sick? GDF15 also functions to suppress immune signaling, helping to prevent the maternal immune system from rejecting the fetus. This immune modulation is thought to be beneficial for the pregnancy, as NVP has been correlated with lower miscarriage rates.

#### Experimental Insights

To test the theory of sensitization to GDF15, researchers conducted experiments on mice. They found that mice with lower baseline levels of GDF15 experienced symptoms of nausea when injected with a medium level of the hormone, while those pre-treated with GDF15 showed reduced responses. This indicates that the body’s baseline level of GDF15 plays a crucial role in determining susceptibility to nausea.

Moreover, studies involving human participants have shown that those with lower GDF15 levels before pregnancy experience less nausea, supporting the idea that the spike in GDF15 during pregnancy is key to understanding NVP.

#### Future Directions

With this new understanding, researchers are considering ways to mitigate NVP. Potential strategies could involve gradual exposure to GDF15 before pregnancy to build tolerance. There are also ongoing investigations into drugs that could block GDF15's action in the brain, similar to treatments being developed for nausea in cancer patients.

While we may not see an FDA-approved anti-morning sickness pill just yet, these insights into GDF15 offer promising avenues for future research and potential treatments.

### Conclusion

Morning sickness, or NVP, remains a complex and poorly understood phenomenon, but recent studies have illuminated its biological underpinnings, particularly the role of GDF15. As scientists continue to unravel these mysteries, there is hope for more effective treatments, allowing pregnant individuals to navigate this challenging aspect of pregnancy with greater ease.