Pregnancy sickness, scientifically known as hyperemesis gravidarum, affects a significant number of pregnant women, impacting their quality of life. Recent groundbreaking research conducted by a dedicated team has shed light on a previously elusive factor contributing to this condition—sensitivity to the hormone GDF15, abundantly produced by the developing pregnancy.
The impact of pregnancy sickness cannot be understated, affecting up to 70% of pregnant women at some point. In severe cases, where nausea and vomiting lead to weight loss or dehydration, approximately 1% to 3% of women suffer. Intriguingly, it ranks as the most common cause of hospitalization during the first trimester. Its repercussions extend beyond pregnancy, with reported psychological distress and reluctance to conceive again among affected women.
The root cause of pregnancy sickness has remained enigmatic, hindering the development of effective treatments and perpetuating societal stigma. However, the team’s research has pinpointed GDF15 as a key player in this complex scenario.
GDF15, a hormone known to suppress food intake in mice, acts on specific brain cells inducing nausea and vomiting. Despite its role in potentially addressing obesity, early trials revealed its side effect—nausea and vomiting. The hormone is notably abundant in the human placenta and reaches high concentrations in the blood of healthy pregnant women, making it a plausible candidate for pregnancy sickness.
Through meticulous analysis, the research team compared GDF15 levels in pregnant women experiencing sickness with those attending hospital for unrelated reasons. Higher GDF15 levels were indeed found in women with pregnancy sickness, suggesting a correlation. However, the overlap in GDF15 levels between the two groups implied additional factors influencing the sickness risk beyond absolute GDF15 amounts.
Delving deeper, the researchers explored the role of DNA variations in maternal genes. Previous studies had identified genetic changes near GDF15 as significant determinants of pregnancy sickness risk. A rare genetic mutation affecting the GDF15 protein’s makeup, present in approximately one in 1,500 people, emerged as a crucial factor in elevating risk.
In laboratory studies, this mutation was found to trap GDF15 inside cells, hindering its transport and creating a double hit effect. Individuals with this mutation exhibited lower GDF15 levels in their blood, aligning with their higher risk of pregnancy sickness. Furthermore, common DNA changes near GDF15, affecting 15% to 30% of people, were associated with lower hormone levels, albeit with a smaller impact on sickness risk.
Strikingly, women with thalassaemia, a blood disorder resulting in high GDF15 levels, reported significantly less nausea and vomiting during pregnancy. This paradoxical observation prompted the researchers to explore hormone sensitivity and memory, where previous exposure influences sensitivity. Mice with persistently high GDF15 levels were less responsive to acute surges, supporting the theory that lower baseline GDF15 levels could make women hypersensitive during pregnancy.
The research concludes that predisposition to higher GDF15 levels when not pregnant may reduce the risk of pregnancy sickness. This seemingly contradictory finding opens avenues for potential treatments. The researchers propose two strategies—desensitizing women to GDF15 by elevating its levels before pregnancy or blocking its action during pregnancy.
The challenge now lies in developing and testing safe and acceptable strategies for women at risk of this debilitating condition. This breakthrough research marks a significant step towards understanding and potentially treating pregnancy sickness, offering hope for improved maternal well-being during this crucial life stage.
