Pregnancy symptoms such as exhaustion, vomiting, and aversion to strong smells are widely recognized, but for approximately 2% of pregnant individuals, these symptoms escalate into a severe condition known as hyperemesis gravidarum. Characterized by frequent vomiting leading to dehydration, weight loss, and potential hospitalization, hyperemesis gravidarum poses risks not only to the expectant parent but also to the developing fetus.
In a groundbreaking study published in Nature, scientists have uncovered new information about the causes of severe nausea and vomiting during pregnancy. The research indicates that the severity of this condition is influenced by the production of a hormone called GDF15 by the growing fetus. Additionally, the study reveals that levels of GDF15 in the parent’s blood before pregnancy can impact their sensitivity to this hormone during gestation.
These findings open avenues for understanding and potentially preventing severe nausea in pregnancy, providing optimism for the development of therapeutic interventions. Zev Williams, a reproductive endocrinologist and director of the Columbia University Fertility Center, hails the research as an exciting avenue, emphasizing the importance of comprehending the causes of pregnancy-related nausea for future prevention strategies.
GDF15, a hormone associated with nausea and tested for its appetite-suppressing properties, is present in the blood of nonpregnant individuals. Levels of GDF15 rise significantly in early pregnancy and continue to increase throughout gestation. Pregnant individuals with higher concentrations of GDF15 have been linked to an elevated risk of vomiting and nausea. Some researchers speculate that the hormone-induced aversion to certain smells and tastes might serve as a protective mechanism, encouraging expectant parents to avoid potentially harmful foods.
To delve deeper into the changes in GDF15 during pregnancy, researchers led by University of Cambridge physician-scientist Stephen O’Rahilly studied pregnant individuals producing a slightly different version of the GDF15 protein, identified through genetic screening. The study found that almost all GDF15 in the parent’s blood originated from the fetus, shedding light on the hormone’s role during gestation.
Analysis of more than 300 participants through questionnaires affirmed that those reporting vomiting and nausea had significantly higher levels of circulating GDF15 than those without these symptoms. Elevated GDF15 levels were also observed in an analysis of over 50 women hospitalized with hyperemesis gravidarum.
However, hormone levels alone did not entirely account for the difference in sickness severity. The study revealed a potential role for individuals’ sensitivity to GDF15 in influencing the severity of symptoms. Additional investigations involving nonpregnant individuals with a genetic variant associated with an increased risk of hyperemesis gravidarum suggested that naturally low levels of GDF15 might predispose someone to sickness during pregnancy.
Animal experiments conducted by O’Rahilly’s team further supported this hypothesis. Mice injected with a single large dose of GDF15 exhibited signs of feeling unwell, such as avoiding food. However, by administering a slow-releasing injection of GDF15 three days before the significant dose, the researchers successfully desensitized the mice to the hormone’s effects, indicating a potential avenue for intervention.
Ruslan Medzhitov, an immunologist at the Yale School of Medicine, described the finding of desensitization as interesting and crucial, addressing the paradox of why low pre-pregnancy GDF15 levels are associated with a higher risk of pregnancy sickness. O’Rahilly suggested that desensitization could explain the common observation that individuals tend to feel less sick as pregnancy progresses, despite high GDF15 levels.
Karen Forbes, a reproductive endocrinologist at the University of Leeds, commended the study as a clever and exciting way to advance the research field. She highlighted the potential clinical implications for individuals at a higher risk of hyperemesis gravidarum, emphasizing the need for further research before implementing treatments based on these findings.
O’Rahilly, who has filed a patent application related to therapeutic applications of this work, expressed a commitment to advancing the research beyond animal studies, actively seeking pharmaceutical partners to translate the findings into clinical applications. The collaborative efforts aim to bring about tangible solutions and improvements for those at risk of severe pregnancy sickness.
