Association Between Maternal Lipid Profile In Early Pregnancy And Preeclampsia

OBJECTIVE:To explore the association of maternal lipid profile in early pregnancy with Preeclampsia.To further analyze and compare the risk of PE caused by dyslipidemia in early pregnancy of women with different pre-pregnancy BMI.And to investigate the different relationship between early onset preeclampsia and late onset preeclampsia and the blood lipid metabolism in early pregnancy.METHODS:Pregnant women who were admitted to Shanghai International Peace Maternity&Child Health Hospital for delivery between January 1st,2015 and December 31st,2017 were recruited as study participants.According to the exclusion criteria:（1）multiple pregnancies;（2）multiparas;（3）pregnant women who did not take blood lipid test in early pregnancy,a total of 32102 pregnant women were recruited,940 of whom developed preeclampsia（23 cases of early onset PE and 917cases of late onset PE）,31162 cases of without preeclampsia women as controls.Blood lipid profiles at 10–14 weeks of gestation and other clinical information were obtained from the electronic medical records.Basic clinical characteristics and serum lipid levels of each group were analyzed.Lipid profile included total cholesterol（TC）,triglycerides（TG）,low density lipoprotein（LDL）,high density lipoprotein（HDL）,apolipoprotein A（Apo A）,apolipoprotein B（Apo B）,lipoprotein a（LPa）,atherosclerosis index（AI）,LRH（LDL/HDL）,BRA（Apo B/Apo A）and TRH（TG/HDL）.The association between serum lipid levels and the risk of preeclampsia was evaluated using adjusted logistic regression models,continuous and categorical（by quartile）effects were both evaluated.Stratified analysis was taken to study the relationship between dyslipidemia and the risk of PE in women with different pre-pregnancy BMI.Sub-group analysis was conducted for early（<34 weeks）and late onset（?34 weeks）preeclampsia,estimating the effect of dyslipidemia by using Multinomial Logistic Regression model.RESULTS:Part 1 Association of maternal lipid profile in early pregnancy with preeclampsiaMean serum TC,TG,LDL,Apo B,AI,LRH,BRA,TRH in early pregnancy in the PE group were on average higher than in the control group（P<0.05）,respectively.The levels of HDL in the PE group were lower than the control group（P<0.05）.TC,TG,LDL,Apo B,AI,LRH,BRA and TRH were independent risk factors for preeclampsia;HDL was the independent protective factor（trend P<0.05）.TG had the greatest impact on the risk of PE among the lipid indexes.Women with TG above1.49mmol/L had a 2 time increased risk（a OR₂ 1.97;95%CI 1.58-2.46）of PE compared to those with TG≤0.93mmol/L.Among four complex indexes,TRH had the greatest effect on PE.The a OR₂ of PE of women with TRH>0.93 was 1.95（95%CI1.55-2.44）.Part 2 Association of maternal lipid profile in early pregnancy with preeclampsia among women with different pre-pregnancy BMIAmong women with pre-pregnancy BMI<18.5kg/m²,TG and TRH in PE group were on average higher than in the control group（P<0.05）;among women with pre-pregnancy BMI:18.5-23.9 kg/m²,serum TG,LDL,Apo B,AI,LRH,BRA and TRH were significantly increased in PE group compared with the controls.Except for TC,the results of women with BMI≥24 kg/m² were the same as those with normal BMI before pregnancy.There was no significant relationship between the lipid profile in early pregnancy and the incidence of PE among women with pre-pregnancy BMI<18.5kg/m².TC,TG,LDL,Apo B,AI,LRH,BRA and TRH showed independent risk effect on the incidence of PE in group of women with normal pre-pregnancy BMI,while HDL had independent protective effect.Except for TC and LDL,the results of overweight（obesity）women before pregnancy were the same as those with normal pre-pregnancy BMI.Part 3 Relationship between early onset preeclampsia and late onset preeclampsia and the dyslipidemia in early pregnancyExcept for LPa,significant differences in levels of blood lipid indexes were found among EPE group,LPE group and control group（P<0.05）.Levels of TC,TG,LDL,Apo B,AI,LRH,BRA,TRH in early pregnancy in EPE and LPE groups were on average higher than in the control group（P<0.05）,respectively.The average level of blood lipid in EPE group was the highest among the three groups.Levels of HDL and Apo A in LPE group were on average lower than in the control group（P<0.05）.The results showed that TC,LDL,AI and LRH were independent risk factors for both EPE and LPE after adjusting for potential confounding factors;the risk of incidence of EPE was greater than LPE.Compare to women with TC≤4.65mmol/L,there was a 4.41-fold increased risk of EPE（a OR₂ 4.41;95%CI 1.26-15.44）and a1.23-fold increased risk of LPE（a OR₂ 1.23;95%CI 1.06-1.43）among women with TC>4.65mmol/L.Women with LDL>2.81mmol/L had a 4.32-fold increased risk of EPE（a OR₂ 4.32;95%CI 1.23-15.20）and a 1.34-fold increased risk of LPE（a OR₂1.34;95%CI 1.15-1.56）.There was a 6-fold risk of EPE（a OR₂ 6.00;95%CI1.34-26.87）and a 1.43-fold risk of LPE（a OR₂ 1.43;95%CI 1.22-1.67）among women with AI>1.71.Compare to women with LRH≤1.64,there was a 3.92-fold increased risk of EPE（a OR₂ 3.92;95%CI 1.10-14.00）and a 1.35-fold increased risk of LPE（a OR₂ 1.35;95%CI 1.15-1.57）among women with LRH>1.64.TG,Apo B and TRH were independent risk factors of LPE,and HDL was the independent protective factor of LPE.CONCLUSIONS:1.Women who develop PE have dyslipidemia in early pregnancy（10-14weeks）;with the increase of blood lipid level,the risk of PE gradually increases.2.With the increase of pre-pregnancy BMI,the degree of dyslipidemia in PE pregnant women gradually increases;the independent effect of dyslipidemia on the risk of PE in early pregnancy is most significant in the pregnant women with normal BMI,followed by overweight and obese pregnant women,but not in lean pregnant women.3.The dyslipidemia indexes of EPE and LPE in early pregnancy are different,and the abnormal lipid metabolism of EPE is more significant;abnormal increase of TC,LDL,AI and LRH in early pregnancy has more significant effect on the risk of EPE.Pathways and timing for the incidence of EPE and LPE caused by dyslipidemia may be different.In conclusion,dyslipidemia in early pregnancy increases the risk of PE.Monitoring blood lipids in early pregnancy is helpful to identify high-risk pregnant women with PE,which can provide referent evidence for clinical diagnosis and treatment.