探讨孕妇血清维生素D、叶酸及血脂水平与其子痫前期(PE)发病风险的相关性。

选择2017年4月至2018年12月，于山东第一医科大学附属中心医院进行产前检查，孕期发生PE，经对症治疗后，于本院分娩的33例孕妇为研究对象。按照发生PE的轻度、重度，分别将其纳入轻度PE组(n＝21)、重度PE组(n＝12)。选择同期在本院分娩的健康孕妇130例，纳入对照组。采集3组受试者一般临床资料，并于早、中、晚孕期(孕龄分别为<12孕周、20～24孕周、32～34孕周)抽取受试者空腹肘静脉血，检测其血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)及维生素D与叶酸水平。采用单因素方差分析或χ²检验，对上述指标进行统计学比较。PE孕妇血清TG、TC、LDL水平与其PE严重程度的相关性分析，采用Spearman秩相关性分析。采用多因素非条件logistic回归分析，对孕妇发生PE的影响因素进行分析。本研究获得山东省医学伦理学委员会批准(审批文号：IACUC20180105)，所有孕妇及其家属签署临床研究知情同意书。3组孕妇早孕期血清TG、TC、LDL、维生素D、叶酸水平比较，差异均无统计学意义(P>0.05)。

①轻度PE组、重度PE组和对照组孕妇的年龄、收缩压、舒张压、孕期体重增加值、孕次、产次、月经周期、月经期及PE家族史、按要求完成产前检查、孕期补充维生素D和叶酸所占比例等分别比较，差异均有统计学意义(P<0.05)。②3组孕妇中孕期血清LDL、维生素D、叶酸水平，以及晚孕期血清TG、LDL、维生素D、叶酸水平分别总体比较，差异均有统计学意义(中孕期：F＝7.061、100.268、73.755，P≤0.001；晚孕期：F＝15.109、18.157、255.431、194.986，P<0.001)。进一步两两比较结果显示，轻度PE组、重度PE组孕妇中孕期血清LDL水平均显著高于对照组，而血清维生素D、叶酸水平，则均显著低于对照组，并且差异均有统计学意义(P<0.05)；重度PE组孕妇中孕期血清维生素D、叶酸水平，均显著低于轻度PE组，并且差异亦均有统计学意义(P<0.05)。重度PE组孕妇晚孕期血清TG、LDL水平，均显著高于轻度PE组与对照组，而血清维生素D、叶酸水平，则均显著低于轻度PE组与对照组，并且差异均有统计学意义(P<0.05)；轻度PE组孕妇晚孕期血清TG、LDL水平，均显著高于对照组，而血清维生素D、叶酸水平，则均显著低于对照组，并且差异均有统计学意义(P<0.05)。③轻度、重度组PE孕妇中，血清TG、TC、LDL水平与其PE严重程度呈正相关关系(r_s＝0.529、0.481、0.533，P<0.001)，而血清维生素D、叶酸水平，则与其PE严重程度呈负相关关系(r_s＝-0.458、-0.473, P<0.001)。④多因素非条件logistic回归分析的结果显示，孕妇收缩压、舒张压、孕次、产次、月经周期、孕期维生素D和叶酸补充情况，以及血清TG、TC、LDL、维生素D、叶酸水平，均为孕妇发生PE的独立影响因素(OR＝2.534、3.547、2.392、2.879、2.653、2.490、2.413、3.319、3.731、2.936、2.012、2.176，95%CI：1.304～4.069、1.363～7.613、1.860～5.397、1.954～6.878、1.238～4.297、1.922～4.874、1.979～5.585、1.027～9.902、1.043～4.144、1.933～4.492、1.480～4.800、1.010～4.309, P<0.05)。

孕妇血清维生素D、叶酸及血脂水平与其PE严重程度密切相关。孕妇孕期补充维生素D、叶酸，及时监测血脂水平，可有效防治PE发生。

To explore correlation of vitamin D, folic acid and blood lipid in pregnant women with the risk of preeclampsia (PE).

A total of 33 pregnant women with PE who underwent prenatal examination and delivered in Central Hospital Affiliated to Shandong First Medical University after symptomatic treatment from April 2017 to December 2018 were selected as research subjects.According to mild and severe PE, they were included into mild PE group (n=21) and severe PE group (n=12), respectively. And 130 healthy pregnant women who gave birth in the same hospital during the same period were selected as control and were included into control group. General clinical data and serum triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), vitamin D and folic acid levels in the first trimester (<12 gestational weeks), second trimester (20-24 gestational weeks) and third trimester (32-34 gestational weeks) were collected. One-way ANOVA or chi-square test was used for statistical comparison of the above index. Spearman correlation coefficient was used to analyze the correlation of serum vitamin D, folic acid and blood lipid levels with the severity of PE. Multivariate unconditional logistic regression was used to analyze influencing factors of PE. This study was approved by Shandong Provincial Medical Ethics Committee (Approval No. IACUC20180105). Clinical research informed consent was obtained from all pregnant women and their family members. There were no statistical differences among three groups in serum levels of TG, TC, LDL, vitamin D and folic acid in the first trimester (P>0.05).

①The age, systolic blood pressure, diastolic blood pressure, weight gain during pregnancy, gravidity, parity, menstrual cycle, menstrual period, and proportions of family history of PE, completion of prenatal examination as required, supplement of vitamin D and folic acid during pregnancy showed statistically significant differences among mild PE group, severe PE group and control group (P<0.05). ②There were statistically significant differences in serum levels of LDL, vitamin D and folic acid in second trimester, and serum levels of TG, LDL, vitamin D and folic acid in third trimester among three groups in overall comparison (second trimester: F=7.061, 100.268, 73.755, P≤0.001; third trimester: F=15.109, 18.157, 255.431, 194.986, P<0.001). Further comparison showed that in second trimester, serum levels of LDL in mild PE group and severe PE group were significantly higher than that of control group, while serum levels of vitamin D and folic acid were significantly lower than those of control group, moreover, serum levels of vitamin D and folic acid in severe PE group were significantly lower than those of mild PE group, and all differences were statistically significant (P<0.05). In third trimester, serum levels of TG and LDL in severe PE group were significantly higher than those in mild PE group and control group, while serum levels of vitamin D and folic acid were significantly lower than those in mild PE group and control group, moreover, serum levels of TG and LDL of pregnant women in mild PE group were significantly higher than those in control group, while serum vitamin D and folic acid levels were significantly lower than those in control group, and all differences were statistically significant (P<0.05). ③Among mild and severe PE pregnant women, serum levels of TG, TC and LDL were positively correlated with severity of PE (r_s=0.529, 0.481, 0.533; P<0.001), while serum levels of vitamin D and folic acid were negatively correlated with severity of PE (r_s=-0.458, -0.473; P<0.001). ④Results of multivariate unconditional logistic regression analysis showed that systolic blood pressure, diastolic blood pressure, gravidity, parity, menstrual cycle, vitamin D and folic acid supplementation during pregnancy, and serum TG, TC, LDL, vitamin D, and folic acid levels all were independent influencing factors of PE in pregnant women (OR=2.534, 3.547, 2.392, 2.879, 2.653, 2.490, 2.413, 3.319, 3.731, 2.936, 2.012, 2.176, 95%CI: 1.304-4.069, 1.363-7.613, 1.860-5.397, 1.954-6.878, 1.238-4.297, 1.922-4.874, 1.979-5.585, 1.027-9.902, 1.043-4.144, 1.933-4.492, 1.480-4.800, 1.010-4.309, P<0.05).

Serum vitamin D, folic acid and lipid levels are closely related to the severity of PE. Vitamin D and folic acid supplementation, and monitoring of blood lipid levels in time during pregnancy can effectively prevent onset of PE.