| Objective:1.To understand the distribution and characteristics of the essential trace element Zinc(Zn)and non-essential trace element Cadmium(Cd)in the urine of pregnant women in Taiyuan during the first trimester,and comprehensively explore the influence of living habits,diet,dietary supplements and other factors on the content of Zn and Cd in the urine of pregnant women.To provide a theoretical basis for reducing insufficient or excessive take of Zn,reducing the impact of Cd toxicity on the health of pregnant women,and exploring effective prevention and intervention strategies to maintain and promote the health of gestational women.2.To study the combined effect of Zn and Cd on the urine metabolomics of gestational women in first trimester in Taiyuan City,and to screen the related biomarkers of the combined effect of high levels of Zn and Cd in pregnancy by metabonomics approach.This study provides a theoretical basis for studying the health effects of combined effects of Zn and Cd in early pregnancy,and to reduce or even eliminate the adverse effects of Cd on pregnant women’s health by supplementing Zn with dietary habits or nutritional supplements.Methods:1.From August 2018 to January 2020,convenience sampling method was used to select gestational women who were treated in the outpatient department of a hospital in Taiyuan as the survey objects.According to the inclusion exclusion criteria,185 pregnant women in the first trimester who completed the Taiyuan Maternal Pregnancy Lifestyle Questionnaire and retained urine samples were finally included.The questionnaire includes information on the general demographic characteristics of pregnant women,living habits,daily diet,and use of nutritional supplements.After the urine specific gravity of the pregnant women was determined,inductively coupled plasma mass spectrometry(ICP-MS)was used to determine the content of essential trace element Zn and non-essential trace element Cd in urine.Epidata 3.1 software is used to enter data,and SPSS 26.0 software is used to analyze data.Frequency,and composition ratio n(%)were used to qualitative data,respectively,and the Kruskal-Wallis H test or Mann-Whitney U test was used to compare between-group distributions.Spearman rank correlation analysis evaluated the relationship between urine Zn and urine Cd content and with other variables(daily diet,nutritional supplement use),and used multiple linear regression analysis to perform multivariate analysis of the influencing factors of urinary Zn and urinary Cd,respectively.2.Based on the results of Zn and Cd content of urine samples of 103 gestational women,the gestational women were separated into 4 groups using 2×2 factorial design:low Zn and low Cd group(Lzn Lcd group),high Zn low Cd group(Hzn Lcd group),low Zn high Cd group(Lzn Hcd group),and high Zn high Cd group(Hzn Hcd group).Subsequently,metabolites in the urine of gestational women in each group were detected by liquid chromatograph mass spectrometer(LC-MS),metabolomic data were analyzed by the multivariate statistical method of partial least squares discriminant analysis(PLS-DA),and the effects of the combined action of Zn and Cd on the urinary metabolome of gestational women.The Area under the curve(AUC)value of the receiver operating characteristic(ROC)is used to diagnose the predictive ability of differential metabolites.The relative content of metabolites in each group was analyzed by factorial design variance.Results:1.Urinary Zn and urinary Cd contents in early pregnancy and their influencing factors.The median content of Zn in the urine of 185 pregnant women was 2713.762ng/ml,the interquartile interval was 2061.680ng/ml to 3410.156ng/ml,the median content of Cd was 0.675ng/ml,the interquartile interval was 0.457ng/ml to 0.998ng/ml.There was no correlation between urinary Zn content and its urinary Cd content(P > 0.05).With each measured urine Zn content(logarithmic conversion)used as a continuous dependent variable,multiple regression equations were established with whether there was pregnancy vomiting in the first trimester,whether eggs and products were consumed,whether fresh vegetables were consumed,the duration of multivitamin use in the year before pregnancy,and whether folic acid was taken since pregnancy as independent variables were introduced into multiple regression and multiple regression equations were established.The coefficients were tested,and the results indicated that the consumption of eggs and products was positively correlated with the urinary Zn content(β = 0.097,95%CI:0.033 ～ 0.161,P = 0.003),the consumption of fresh vegetables was negatively correlated with urinary zinc content(β =-0.169,95%CI:-0.322 ～-0.017,P = 0.030)and consumption of folic acid was negatively correlated with urinary zinc content(β =-0.093,95%CI:-0.165 ～-0.021,P = 0.011).No other variables were found to have significant effects on urinary Zn content in pregnant women(P > 0.05).With each measured urine Cd content(logarithmic conversion)used as a continuous dependent variable,multiple regression equations were established with the maternal education,the number of pregnancies and the number of weekly intakes of folic acid since pregnancy as the independent variable were introduced into multiple regression and multiple regression equations were established.The coefficients were tested,and the results indicated that the number of pregnancies was positively correlated with urinary Cd content(β = 0.049,95%CI: 0.004 ～ 0.095,P = 0.032),and the number of weekly intakes of folic acid since pregnancy was negatively correlated with urinary Cd content(β =-0.023,95%CI:-0.040 ～ 0.007,P = 0.005).No other variables were found to have significant effects on urinary Cd content in pregnant women(P > 0.05).2.Effect of Zn and Cd on urine metabolomics in early pregnancy.The results of urinary metabolomics showed that a total of 931 metabolites were detected in positive ion mode through VIP value >1 and P < 0.05 based on the PLS-DA model established by the combined action group of Zn and Cd(Hzn Hcd group),including890 metabolites up-regulated and 23 down-regulated.A total of 583 metabolites were detected in negative ion mode,of which 350 were up-regulated and 233 were down-regulated.In the positive ion mode,arginine and proline metabolism were the key pathways with the strongest correlation with differential metabolites.In the negative ion mode,the biosynthesis of pantothenate and coa was the key pathway with the highest correlation with differential metabolites.From the screened differential metabolites,51 differential metabolites were further obtained by Fold change(Fc)> 2 or Fc < 0.5.In the positive ion model,there were 46 differentially expressed metabolites,all of which were up-regulated.In the negative ion model,there were 5 metabolites,all of which were up-regulated.The results of the analysis of variance showed that there were additive and antagonistic effects among the biomarkers related to the joint effect of Zn and Cd.In addition,the diagnostic efficacy of 51 metabolites was evaluated by AUC value analysis of ROC curve,and it was found that AUC were all > 0.5.Conclusions:1.In this study,the contents of Zn and Cd in the urine of pregnant women were mainly affected by dietary factors.The consumption of eggs and fresh vegetables affected the contents of Zn and Cd in urine,while the intake of folic acid also affected the contents of Zn and Cd in urine.In health care work,interventions such as dietary habits and nutritional supplements can help pregnant women maintain the dynamic balance of Zn and Cd contents and promote health care during pregnancy.2.This study found that the key pathways with the highest enrichment and the highest correlation with differential metabolites in positive and negative ion modes were arginine and proline metabolism and pantothenate and coenzyme A biosynthesis,respectively.The differential metabolites and metabolic pathways changed in early pregnancy are of great significance for understanding the mechanism of the combined health effects of Zn and Cd in normal pregnant women,screening related biomarkers,and providing a theoretical basis for early prevention strategies combined with daily diet and nutritional supplement intake on the adverse health effects of pregnant women and fetuses.It also provides a reference for the pathogenesis of pregnancy-related diseases such as gestational diabetes mellitus. |
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