维生素D与原因不明复发性流产患者免疫相关性的系统评价

Systematic review of correlation between vitamin D and immunity in patients with unexplained recurrent spontaneous abortion

目的系统评价维生素D与原因不明复发性流产(URSA)患者免疫的相关性。方法计算机检索PubMed、EBSCO、CNKI、CBM、VIP和WanFang Data数据库,搜集有关维生素D和URSA患者免疫相关的对照研究,检索时间从建库至2021年1月。病例对照研究中URSA作为试验组,正常妊娠女性作为对照组。随机对照试验中,对URSA患者进行分组,分为试验组和对照组。病例对照研究无干预措施。随机对照试验的干预措施为试验组和对照组患者均给予常规治疗,试验组在对照组干预措施的基础上加用维生素D。由两位研究者独立筛选文献、提取资料,对纳入研究质量评价后,采用RevMan 5.3软件进行meta分析。结果共纳入12篇文献,共2114例受试者。meta分析结果显示,试验组的25-羟维生素D[25(OH)D]水平低于对照组,差异有统计学意义[SMD=-1.46,95%CI(-2.08,-0.84),P<0.00001];25(OH)D<30 ng/ml组URSA患者的抗甲状腺过氧化物酶抗体(TPOAb)、抗心磷脂抗体(ACA)、抗核杭体(ANA)阳性率高于25(OH)D≥30 ng/ml组,差异有统计学意义[OR=3.87,95%CI(2.27,6.60),P<0.00001;OR=2.96,95%CI(1.53,5.75),P=0.001;OR=2.54,95%CI(1.54,4.17),P=0.0002];25(OH)D<30 ng/ml组URSA患者的CD4^(+)T、CD56^(+)NK细胞计数高于25(OH)D≥30 ng/ml组,差异有统计学意义[SMD=1.65,95%CI(1.29,2.01),P<0.00001;SMD=0.83,95%CI(0.35,1.31),P=0.0008];而25(OH)D<30 ng/ml组与25(OH)D≥30 ng/ml组URSA患者的CD19^(+)B细胞计数比较,差异无统计学意义[SMD=1.74,95%CI(-1.07,4.56),P=0.22];试验组URSA患者的流产率低于对照组URSA患者,差异有统计学意义[RR=0.53,95%CI(0.31,0.89),P=0.02]。结论25(OH)D缺乏与增加的CD4^(+)T、CD56^(+)NK细胞计数和自身免疫抗体相关,补充足量的维生素D可能具有预防URSA的作用。但本研究受纳入研究对象数量和质量的限制,结论尚需开展更多高质量研究予以验证。

Objective To conduct a systematic review of the correlation between vitamin D and immunity in patients with recurrent miscarriage(URSA).Methods PubMed,EBSCO,CNKI,CBM,VIP,and WanFang Data databases were searched for control studies related to vitamin D and immunity in patients with URSA.The search time limit was from the establishment of the database to January 2021.In the case control study,patients with URSA were as the experimental group and normal pregnant women as the control group.In the randomized controlled trial,patients with URSA were divided into experimental group and control group.The case control study had no intervention.In the randomized controlled trial,both the experimental group and the control group were given routine treatment,and the experimental group was given vitamin D in addition to the intervention of the control group.The studies were screened by two independent researchers and data were extracted.After quality evaluation of included studies,RevMan 5.3 software was used for meta-analysis.Results A total of 12 literatures were included,including 2114 subjects.Meta-analysis results showed that the level of 25-hydroxyvitamin D(25[OH]D)in experimental group was lower than that in control group,the difference was statistically significant(SMD=-1.46,95%CI[-2.08,-0.84],P<0.00001).The positive rates of anti-thyroid peroxidase antibody(TPOAb),anticardiolipin antibody(ACA)and antinuclear antibody(ANA)in URSA patients of 25(OH)D<30 ng/ml group were higher than those in URSA patients of 25(OH)D≥30 ng/ml group,and the differences were statistically significant(OR=3.87,95%CI[2.27,6.60],P<0.00001;OR=2.96,95%CI[1.53,5.75],P=0.001;OR=2.54,95%CI[1.54,4.17],P=0.0002).CD4^(+)T and CD56^(+)NK cell counts in URSA patients of 25(OH)D<30 ng/ml group were higher than those in URSA patients of 25(OH)D≥30 ng/ml group,the differences were statistically significant(SMD=1.65,95%CI[1.29,2.01],P<0.00001;SMD=0.83,95%CI[0.35,1.31],P=0.0008).There was no significant difference in CD19^(+)B cell count between the URSA patients of 25(OH)D<30 ng/ml group and the URSA patients of 25(OH)D≥30 ng/ml group(SMD=1.74,95%CI[-1.07,4.56],P=0.22).The abortion rate of URSA patients in experimental group was lower than that of URSA patients in control group,and the difference was statistically significant(RR=0.53,95%CI[0.31,0.89],P=0.02).Conclusion Deficiency of 25(OH)D is associated with increased CD4^(+)T CD56^(+)NK cell counts and autoimmune antibody,and adequate vitamin D supplementation may prevent URSA.However,this study was limited by the number and quality of subjects included in the study,and the conclusion needs to be verified by more high-quality studies.