| Objective:1.To explore the correlation between serum homocysteine,folic acid,vitamins B12,fasting blood glucose(FBG)and lipid profiling(TC,TG,LDL-C,HDL-C)in first trimester and hypertensive disorders of pregnancy(HDOP).2.To investigate the correlation between serum homocysteine,folic acid,vitamin B12 level in first trimester and the incidence of gestational hypertension and preeclampsia respectively.3.To explore the correlation between serum homocysteine,folic acid,vitamin B12 level in first trimester and the severity of preeclampsia.4.To investigate the novel differential metabolites in cases with hypertensive disorder of pregnancy by using the gas chromatography coupled with mass spectrometry(GC-MS).Methods:1.Retrospective analysis the data at International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University from October 2015 to January 2016.Pregnant women who underwent their prenatal screening in our hospital and delivery of singleton pregnant women were collected.257 cases diagnosed hypertensive disorders of pregnancy(study group)and 1020 cases with normal blood pressure,no proteinuria in pregnancy(control group)were selected.Maternal blood samples were collected between 11 and 13weeks of gestation to test serum concentrations of homocysteine(Hcy),folic acid,Vitamin B12,FBG and lipids profile.Maternal characteristics and pregnancy outcomes were collected for each woman.Logistic regression was conducted to calculate adjusted odds ratios (aORs)and 95%confidence intervals(CIs).2.Retrospective cohort were conducted from January 2016 to June 2016 in International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University.In accordance with the inclusion and exclusion criteria,a total of 4712 pregnant women were collected in this cohort study.Finally,there are 147 pregnant women diagnosed preeclampsia(including 103 mild preeclampsia cases,44 severe preeclampsia cases),147 diagnosed gestational hypertension.4418 pregnant women with normal blood pressure and nonproteinuric throughout pregnancy were served as a control group.Maternal blood samples were collected between 11 and 13 weeks of gestation to test serum concentrations of homocysteine(Hcy),folic acid,and VitB12.A logistic regression model was used to calculate adjusted odds ratios(aORs)and 95%confidence intervals(CIs).3.15 patients who were diagnosed hypertensive disorders of pregnancy(HDOP)and22 control patients(age matched)from September 2016 to November 2016in International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University were enrolled in this study.GC-MS were used to discover the different metabolomic profiles between two groups.Score plots of orthogonal partial least-squares discriminant analysis(OPLS-DA)clearly separated the HDOP group from the control group.The variable importance in projection(VIP)generated in OPLS-DA processing represented the contribution to the discrimination of each metabolite ion between groups.Variables with a VIP>1 and P<0.05 were considered to be different variables.We also used MetaboAnalyst 3.0 to analyze the pathway impact of potential metabolite biomarkers.Results:1.Women who were nulliparous were more likely to develop HDOP(85.6%vs.73.4%,p<0.001).Women who developed HDOP had a conspicuously higher rate of assisted reproduction(12.06%vs.6.67%,p<0.05)and a family history of hypertension than those in control(24.51%vs.18.73%,p<0.05).There were no significant differences in age and educational levels between the two groups.2.As for the pregnancy outcomes,the rate of preterm delivery(gestational week<37)in HDOP was higher than that in control group(12.84%vs.3.73%,p<0.001).Women in HDOP had a higher rate of caesarean section than those in control group(67.7% vs.49.8%,p<0.001).The average birth weight and birth height of offspring in HDOP were lesser than those in control group(p=0.031 and 0.02,respectively).While there were no significant differences in offspring sex between the two groups(p=0.831).3.The proportion of overweight(BMI 24–27.9 kg/m~2)or obesity(BMI≥28kg/m~2)in HDOP was significantly higher than that in the control group(33.8%vs.14.4%,p<0.001).The mean total gestational weight gain(GWG)among women who developed HDOP was higher than that of control women(median:16.89 vs.14.69kg,p<0.001).Meanwhile the GWG in women of HDOP was more liable to exceed the recommendation than that in control(65.76%vs.42.84%,p<0.001).In addition,women who developed HDOP had a higher rate of excessive gestational BMI gain(kg/m~2)than that in control(5.4%vs.1.5%,p<0.001).4.In the model adjusted for confounders,pre-pregnancy BMI and GWG were all positively associated with the risk of HDOP.Women who were overweight(BMI 24–27.9 kg/m~2)prior to pregnancy were about 2 times more likely to develop HDOP,compared with women who had a normal pre-pregnancy BMI(aOR 2.038,95%CI1.362,3.049).Women who were obese prior to pregnancy were about 3 times more likely to develop HDOP,compared with women who had a normal pre-pregnancy BMI(aOR 3.36,95%CI 1.623,6.956).A significantly increased risk of HDOP was also observed for women with GWG above the IOM recommendation(aOR 1.503,95%CI 1.028,2.195).5.Hcy,FBG,TG,LDL-C,levels were significantly higher in HDOP subjects than those in controls(p<0.05),whereas the plasma HDL-C and VitB12concentrations were significantly lower in HDOP cases than those in control group(p<0.05).Total cholesterol(TC)and folic acid concentrations were not statistically different between two groups(p>0.05).6.After using Logistic regression analyses for the potential confounding factors,we found that higher Hcy and FBG concentrations were positively associated with HDOP(aOR=1.15,95%CI=1.027,1.293 and aOR=2.15,95%CI=1.546,3.012,respectively).While significant association did not persist in lipids profile(TC,TG,HDL-C,LDL-C)、folic acid、VitB12 and HDOP after control for confounding factors.7.Cohort study showed that women who subsequently developed GH and PE were generally older than those in the control group(p=0.028 and 0.016,respectively).BMI was higher in women who later developed GH and PE(p<0.001).Compared with the control group,women who developed PE were less educated(p=0.031),while those who developed GH were more often primiparous(p=0.012).As for the pregnancy outcomes,the delivery weeks in GH and PE were lower than those in the control group.The discrepancies were significant(p=0.009 and<0.001 respectively).Furthermore,neonatal birth weights in the PE group were significantly lower than those in the control group(3.35±0.43 vs.3.11±0.66 kg,P<0.001).8.Women who subsequently developed severe PE had higher concentrations of Hcy than those in the control group(8.50±1.18 vs.7.33±1.53μmol/L,P<0.001).Women with GH and mild PE had slightly higher concentrations of Hcy as compared with control subjects;however,this did not reach statistical significance.Serum concentrations of folic acid and VitB12 were similar among the various groups.9.After adjusting for confounders,we found that women with higher concentrations of Hcy had a 1.12-fold increased risk of severe PE as compared with those in the control group(aOR1.12,95%CI,1.06–1.20).However,it is not a useful marker for the subsequent development of GH or mild PE.10.Fourty-seven metabolites were significantly different between the two groups,as indicated by a VIP>1 and P<0.05.Levels of 17 micromolecular metabolites were significantly increased(P<0.05),and those of 30 micromolecular metabolites were significantly decreased(P<0.05).The metabolic Pathways involving Alanine,aspartate and glutamate metabolism(P=0.000378,impact=0.37),Glycine,serine and threonine metabolism(P=0.00003,impact=0.29),beta-Alanine metabolism(P=0.0008,impact=0.28),Histidine metabolism(P=0.03,impact=0.20),Lysine Biosynthesis (P=0.01,impact=0.18),Nicotinate and nicotinamide metabolism(P=0.03,impact=0.12)are obviously related to HDOP.Conclusion1.The Pre-Pregnancy Body mass index(BMI),total gestational weight gain(GWG)and high serum homocysteine and fasting blood glucose(FBG)levels in first trimester were high risk factors for the occurrence of HDOP.2.Although there were significant differences in blood lipid profiling in first trimester between HDOP and the control group,there was no significant correlation between lipid profiling and the occurrence of HDOP.3.Our study found that the level of serum homocysteine in first trimester is an independent risk factor for severe preeclampsia.However,it is not a useful marker for the subsequent development of GH or mild PE.4.Compared with the normal control group,serum folic acid and vitamin B12 levels in first trimester were not different in pregnant women with GH and PE.5.GC-MS showed different characteristics of Plasma metabolism compared to the controls.Significant change in the levels of some metabolites may be accompanied with abnormality in many metabolism pathways in HDOP. |
