Hyperemesis gravidarum (HG) is severe nausea and vomiting in pregnancy. Between 0.3 %- 3 % of all pregnant women suffer from HG [1]. Worldwide, prevalence rates are higher in women of Asian and Middle Eastern ethnicities, as high as about 10 % in a study of a Chinese population [2]. HG can be complicated by dehydration, electrolyte disturbances, poor nutritional intake, weight loss, and requires hospitalization in most cases [3]. In addition to the negative effects on maternal, physical, and psychological well-being, HG can impair fetal growth and have negative consequences for the health of the offspring.

Vitamin D, a fat-soluble vitamin, is the collective name for cholecalciferol and ergocalciferol [4]. 25-Hydroxyvitamin D (25OHD) is the main form of vitamin D in the human bloodstream and is often used as an indicator for evaluating the nutritional status of vitamin D. Therefore, in this work, we focus on serum 25OHD levels. Evidence is accumulating that vitamin D deficiency increases the risk of adverse perinatal outcomes [5]. There are preliminary studies suggesting that vitamin D levels were lower in women with hyperemesis gravidarum compared to others [6]. Vitamin D is an immunomodulator that may play a crucial role in the development of hyperemesis gravidarum. Therefore, vitamin D is thought to play a crucial role in controlling the inflammatory status associated with hyperemesis gravidarum.

Because of the special nature of pregnancy, randomization clinical trials researches (RCTs) are limited. In the absence of RCTs, Mendelian randomization (MR) design is an important strategy for causal inference. MR uses genetic variants as proxies for an exposure to predict its causal association with an outcome. This method skillfully exploits the genetic variation's distributive randomness while successfully avoiding confounding biases [7].

Overall, the relationship between vitamin D levels and the risk of HG is still not clear, and further studies are need. In this study, we focused on exploring the causal relationship between serum 25OHD level and the occurrence of HG, which may have significant clinical potential.