Vitamin D and hyperemesis gravidarum: A Mendelian randomization study - Oct 2023
J Gynecol Obstet Hum Reprod . 2023 Oct 20:102678. doi: 10.1016/j.jogoh.2023.102678
Fang Hu 1
Background: The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method.
Methods: Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum.
Results: We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95% CI: 0.403-0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population.
Conclusions: The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.
Introduction
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 population2. 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 outcomes5. There are preliminary studies suggesting that vitamin D levels were lower in women with hyperemesis gravidarum compared to others6. 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.
Section snippets
Study design
MR is a method for determining the causal relationship between the phenotype of exposure and the outcome by using genetic variants for exposure as instrument variables (IV) 8. This method could use the publicly available dataset from large-sample genome-wide association studies (GWAS) for both “exposures” and “outcomes” and address the common drawbacks of observational studies. To obtain reliable causal relationships, MR studies must meet the assumptions of relevance assumptions (IVs are . . . . .
Instrumental variable selection
Independent SNPs were selected from the GWAS dataset, which were associated with the 25OHD serum level at the genome-wide significance level (p < 5 × 10−8) and the low level of linkage disequilibrium (LD) (r2 < 0.001) were related. Removing the following SNPs because they are palindromic and have intermediate allele frequencies: rs10127775, rs5112. The genes in which they occur were queried in Pubmed, and the genes of SNPs that do not belong to a specific gene were defined as NULL. The . . . . .
Discussion
The Mendelian randomization study performed an analysis of the causal relationship between vitamin D and HG based on GWAS summary datasets generated by many different consortia including 441,291 individuals using multiple SNPs as instrumental variables. Our results showed a causal relationship between serum 25OHD level and the occurrence of HG.
A previous research showed that vitamin D levels were lower in women with hyperemesis gravidarum compared to other women although it did not reach. . . . .
Conclusion
In the MR study, we found that decreases in serum 25OHD levels were associated with a higher risk of HG, which is consistent with previous studies describing a critical biological role of vitamin D in the development of HG. However, because of the limited availability of evidence from clinical studies, further clinical studies are needed to investigate the benefits of vitamin D for the prevention and treatment of HG.
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Cited by (0)
Evaluation of Maternal Serum 25-Hydroxyvitamin D Levels in Patients with Hyperemesis Gravidarum at Early Gestational Weeks - 2020
Eliras J Fam Med 2020;9(3): 123-30. doi: 10.33880/ejfm.2020090302
Burcu Kayili, Muhammet Ali Oruç, Yasemin Alan, Murat Alan, Deniz Can Öztekin
Aim: The aim of this study was to compare vitamin D levels between pregnant women with hyperemesis gravidarum before 12 weeks of gestation and healthy pregnant women at similar ages.
Methods: Sixty pregnancies with hyperemesis gravidarum and 60 age compatible healthy pri applied to our facility were included in the study. Demographic characteristics, maternal thyroid tests and 25-Hydroxyvitamin D levels were evaluated. Student t test was used for the variables w distribution and Mann-Whitney U test was used to analyze the variables without normal distributi
Results: Only one pregnant woman had normal vitamin D levels (>30ng/ml), whereas 71 pi deficiency (10-30 ng/ml), and 48 had severe deficiency (<10 ng/ml). The mean vitamin D level o 120 pregnancies was 11.9±5.00 ng/ml (9.92±3.67 ng/ml in case group, 13.88±5.38 ng/ml in conti The mean value of vitamin D was found to be significantly lower in hyperemesis gravidarum. 45 of the pregnant women had vitamin D deficiency, whereas 55% (n=33) of them had severe deficie T3 and T4 levels were significantly higher than the control group, and thyroid-stimulating hormone significantly lower.
Conclusion: Vitamin D levels of pregnant women with hyperemesis gravidarum were significantly lower. Vitamin D deficiency should be considered in patients with hyperemesis gravidarum.
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