| Objective:During non-pregnancy,hyper-homocysteine is defined as > 15 μmol/L,which is one of the independent risk factors of coronary atherosclerosis heart disease.However,changes of homocysteine during pregnancy and the influence factors of homocysteine are still controversial,and the impact of homocysteine during pregnancy to pregnancy outcome(such as preeclampsia,fetal intrauterine growth restriction,gestational diabetes,recurrent miscarriage,placental abruption,premature birth,thromboembolic disease,etc.)remains uncertain.Therefore,this study will focus on the risk factors affecting homocysteine during pregnancy,the changes of homocysteine in different gestational weeks and its influence on adverse pregnancy outcomes.Methods:1.This is a prospective study.1142 singleton pregnancy who receive regular prenatal care in the International Peace Maternal and Child Health Hospital affiliated to eh school of medicine of Shanghai Jiaotong University from July to September 2018 were selected.Their blood samples were collected during the first trimester(10-14weeks),the second trimester(24-28 weeks),and the third trimester(30-34 weeks).2.Laboratory test: Peripheral blood samples from into the object,after centrifugal treatment,serum specimens preserved in-80℃ refrigerator,using circulating enzymatic homocysteine detection,by using chemiluminescence detection of folate,vitamin B12,blood specimens preserved in-80℃ refrigerator,used to extract DNA,further probe method is used to detect MTHFR rs1801133,MTHFR rs1801131,MTHFR rs17367504 genotype.3.Clinical data Collecting:(1)general information(including age,education level,smoking history,drinking history,fertility history,method of conception,pre-pregnancy BMI and blood pressure in early pregnancy);(2)blood biochemical results and glucose tolerance results in early pregnancy;(3)pregnancy outcomes(gestational weeks,pre-delivery blood pressure,delivery methods,gestational hypertension,intrauterine growth restriction,gestational diabetes,intrahepatic cholestasis,placental abruption,stillbirth,thromboembolic disease,placenta previa,neonatal weight,Apgar score).4.Statistics analysis: Finishing the above the collected data and test results,according to single factor linear model and multiple linear model to determine the risk factors of homocysteine,folic acid,vitamin B12,after correction,explore the changes of homocysteine,folic acid,vitamin B12 during pregnancy and their correlation in the same period,and discuss the impacts of homocysteine,MTHFR on adverse pregnancy outcomes.Results:1.The mean level of homocysteine in different gestations was 4.36±1.05 μmol/L(10-14weeks),5.95±1.46 μmol/L(24-28 weeks),and 5.95±1.74 μmol/L(30-34 weeks).2.During pregnancy,homocysteine was significantly lower than that in the second and third trimesters,while folic acid and vitamin B12 were significantly higher than that in the second and third trimesters.Serum homocysteine,folic acid and vitamin B12 had no significant difference in the second and third trimester of pregnancy.3.Homocysteine was negatively correlated with folic acid and vitamin B12 in the first trimester,the second trimester and the third trimester,respectively.4.Previous preeclampsia history,creatinine,albumin,globulin and MTHFR rs1801133 T mutation were all influencing factors for homocysteine elevation during pregnancy.The G mutation of MTHFR gene rs17367504 is the influencing factor of homocysteine decline in pregnancy.There was no significant correlation between homocysteine in pregnancy and age,mode of conception,history of previous spontaneous abortion and history of retained abortion.5.The three MTHFR genes had no significant correlation with folate and vitamin B12 levels.6.Elevated homocysteine levels in the third trimester of pregnancy significantly increased the risk of preeclampsia(especially early-onset preeclampsia and severe preeclampsia)and preterm delivery,which was negatively correlated with neonatal weight,but not significantly correlated with the risk of gestational hypertension,GDM,ICP,stillbirth,and postpartum hemorrhage.7.Homocysteine in early pregnancy is a protective factor for thromboembolic disease,but it is not significantly associated with hypertension,preterm delivery,FGR,GDM,ICP,stillbirth,and postpartum hemorrhage.8.MTHFR rs1801133 was not significantly associated with the risk of hypertensive disease,preterm delivery,FGR,thromboembolic disease,GDM,ICP,postpartum hemorrhage and stillbirth.MTHFR rs1801131 increases the risk of early-onset preeclampsia.GG homozygous mutation of MTHFR rs17367504 may increase the risk of hypertensive disease during pregnancy,but is not significantly associated with the risk of other adverse pregnancy outcomes.Conclusions:1.T mutation of MTHFR rs1801133,folic acid and vitamin B12 deficiency during pregnancy were the most critical factors influencing the increase of homocysteine levels during pregnancy.The G mutation of MTHFR gene rs17367504 may cause the decrease of homocysteine level in pregnancy.2.Homocysteine is lowest in the first trimester of pregnancy(10-14 weeks)and gradually rises to a plateau at 24 weeks,which may be associated with a significantly lower level of folic acid and vitamin B12 in the third trimester of pregnancy than in the first trimester.Deficiency of folic acid and vitamin B12 during pregnancy may cause an increase in homocysteine during pregnancy,and supplementation with folic acid and B vitamins may reduce homocysteine during pregnancy.3.MTFHR may not directly cause adverse pregnancy outcomes,but it can lead to elevated homocysteine,which can lead to adverse pregnancy outcomes(e.g.,preeclampsia,FGR,preterm birth).4.There was no significant correlation between homocysteine in early pregnancy and adverse pregnancy outcome.Increased homocysteine in the third trimester of pregnancy significantly increased the risk of preeclampsia(especially early-onset preeclampsia and severe preeclampsia)and preterm delivery,which was negatively correlated with neonatal weight,but not significantly correlated with other adverse pregnancy outcomes such as gestational hypertension,GDM and ICP.5.This study’s pregnancy homocysteine scope is as follows(P2.5-P97.5):(1)1st trimester(10-14 weeks): 2.7-6.62μmol/L;(2)2nd trimester(24 to 28 weeks): 3.8-9.63μmol/L;(3)3rd trimester(30-34 weeks): 3.6-9.96μmol/L;(4)the median level of Hcy during 1st,2nd and 3rd trimester is 4.3μmol/L,5.7μmol/L,5.5μmol/L,respectively. |
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