Exploration On The Relationship Between Fat-soluble Vitamins And Preeclampsia In Pregnant Women And The Mechanism Of Th1/Th2 Immune Balance

ObjectiveThe current study was conducted to explore the association between the levels of dietary/serum fat-soluble vitamins and the risk of preeclampsia（PE）,and the relationship between fat-soluble vitamins and Th1/Th2 immune balance in the pathogenesis of PE,then provide scientific basis for instructing pregnant women to supply fat-soluble vitamins reasonably as well as prevent PE.MethodsThis case-control study was conducted in the First Affiliated Hospital of Zhengzhou University from March 2016 to June 2019.A total of 165 pregnant women with PE were included as the case group.The control group included 217 pregnant women without PE.A questionnaire survey was performed to collect essential information of the subjects.Food frequency questionnaire（FFQ）was used to investigate the dietary intake of the subjects in the three months before delivery.The intake of nutrients and fat-soluble vitamins of each group of pregnant women was calculated according to the food composition table.The venous blood of the subjects before delivery was collected,and the levels of serum fat-soluble vitamins and immune cell secretion factors were detected by liquid chromatography-tandem mass spectrometry（LC-MS）and enzyme-linked immunosorbent assay（ELISA）.The database was established by using software SPSS 21.0 and statistical analysis was performed via software SPSS 21.0.α=0.05.To compare the differences between the case group and control group,the independent sample t test was used for normally distributed variables,the nonparametric test was used for non-normally distributed variables,and theχ² test was used for frequency variables.According to the quartile of the control group’s diet and serum fat-soluble vitamins levels,the study subjects were divided into four groups from low to high levels.Logistic regression analysis was conducted to explore the relationship between fat-soluble vitamins and the risk of PE.Restricted cubic spline（RCS）was carried out to analyze the nonlinear relationship between fat-soluble vitamins and PE risk.Mediation effects and interactions analysis were performed to explore the relationship between fat-soluble vitamins and Th1/Th2immune balance in the pathogenesis of PE.Results1.There were no significant differences in age and gestational weeks between the case group and the control group（P>0.05）,and the two groups were balanced and comparable.Compared with the control group,the case group had more weight gains during pregnancy,lower education level,and the ratio of family history of hypertension,first pregnancy,irregular menstruation,and dysmenorrhea were higher.The differences were statistically significant（P<0.05）.2.The average daily intakes of energy,protein,carbohydrate,and fruits in the case group were lower than that in the control group,and the differences were statistically significant（all P<0.05）.Besides,the vitamin A and vitamin D intake levels of the case group and the control group were significantly different（all P<0.05）.There were also significant differences in serum vitamin A,vitamin E,vitamin D₂,vitamin D₃,and total vitamin D levels between the two groups（all P<0.05）.ELISA results showed that the serum levels of immune cytokines IL-17A,IL-2,IL-4,INF-γ,TNF-α,and TGF-βin the case group were significantly higher than those in the control group（all P<0.05）.3.Logistic regression analysis showed that,compared with the lowest group,the odds ratio（OR）and 95%confidence interval（CI）of the highest dietary vitamin A intake group were 0.37（0.16,0.89）.The OR and 95%CI of PE of the highest dietary vitamin D intake were 0.36（0.16,0.77）.The OR and 95%CI of PE of the highest serum vitamin A/D₂/D₃/D/E level were 2.25（1.09,4.68）,0.11（0.04,0.27）,0.37（0.18,0.78）,0.29（0.14,0.61）,and 11.86（4.87,28.87）,respectively.4.The RCS results showed that only dietary vitamin A intake,serum vitamin D₃and total vitamin D levels had a nonlinear relationship with the risk of PE（P<0.05）.5.There was no mediating effect between serum fat-soluble vitamins and Th1/Th2immune balance in the occurrence and development of PE（P>0.05）.There was an interaction between vitamin D₂ and Th1/Th2 immune balance in the process of PE（P=0.042）.Conclusions1.Insufficient dietary vitamin A and vitamin D intake may be risk factors for PE.2.Excessive serum vitamin A and vitamin E levels may be risk factors for PE.Adequate serum vitamin D₂,D₃ and total vitamin D levels may be protective factors for PE.3.Fat-soluble vitamins do not affect the occurrence and development of PE by regulating the Th1/Th2 immune balance,but there may be a mechanism link between the serum vitamin D₂ and Th1/Th2 immune balance of PE patients.