胎儿生长受限孕妇血清microRNA-424、sFlt-1 mRNA相对表达量对叶酸、维生素B12水平的影响

Effects of serum microRNA-424 and sFlt-1 mRNA expression on FA and VitB12 levels in pregnant women with fetal growth restriction

摘要:

目的 探讨胎儿生长受限孕妇血清microRNA-424（miR-424）、可溶性血管内皮生长因子受体-１（sFlt-1）mRNA相对表达量对叶酸（FA）、维生素B₁₂（VitB₁₂）水平的影响。方法 回顾性分析2017年1月—2019年1月在石家庄市妇幼保健院住院分娩的116例胎儿生长受限孕妇（FGR组）和116例分娩正常胎儿孕妇（对照组）的临床资料。采用实时荧光定量PCR检测miR-424 mRNA、sFlt-1 mRNA相对表达量，采用电化学发光法检测FA、VitB₁₂水平。比较两组胎儿生长参数［出生体重、身高、腹围、头围、体质量指数（BMI）］、miR-424 mRNA、sFlt-1 mRNA、FA及VitB₁₂；采用Pearson法分析血清各指标与胎儿生长参数的相关性及血清miR-424 mRNA、sFlt-1 mRNA与FA、VitB₁₂的相关性；采用受试者工作特征（ROC）曲线分析血清miR-424 mRNA、sFlt-1 mRNA预测胎儿生长受限的效能。结果 FGR组胎儿出生体重、身高、腹围、头围及BMI低于对照组（P <0.05）；FGR组miR-424 mRNA、sFlt-1 mRNA相对表达量高于对照组，FA、VitB₁₂水平低于对照组（P <0.05）；miR-424 mRNA和sFlt-1 mRNA与胎儿出生体重、身高、腹围、头围及BMI呈负相关（P <0.05）；FA和VitB₁₂与胎儿出生时体重、身高、腹围、头围及BMI呈正相关（P <0.05）。miR-424 mRNA预测胎儿生长受限的AUC为0.790，截断值>0.18时，敏感性为74.14%（95% CI：0.476，0.790），特异性为71.55%（95% CI：0.378，0.800）；sFlt-1 mRNA预测胎儿生长受限的AUC为0.777，截断值> 6.39时，敏感性为56.03%（95% CI：0.448，0.664），特异性为91.38%（95% CI：0.207，0.985）；FA预测胎儿生长受限的AUC为0.826，截断值≤ 11.24 μg/L时，敏感性为85.34%（95% CI：0.576，0.892），特异性为66.38%（95% CI：0.500，0.716）；VitB₁₂预测胎儿生长受限的AUC为0.831，截断值≤ 255.24 ng/L时，敏感性为85.34%（95% CI：0.322，0.948），特异性为67.24%（95% CI：0.517，0.802）；各指标联合预测胎儿生长受限的AUC为0.909，敏感性为85.34%（95% CI：0.672，0.957），特异性为82.76%（95% CI：0.767，0.905）（P <0.05）；血清miR-424 mRNA和sFlt-1 mRNA与FA和VitB₁₂呈负相关（P <0.05）。结论 胎儿生长受限孕妇血清miR-424 mRNA、sFlt-1 mRNA呈高表达，并能通过影响FA、VitB₁₂水平，负调控胎儿生长发育，检测各指标有望成为预测胎儿生长受限的一个血清学方法。

Abstract:

Objective To investigate the effects of serum microRNA-424 (miR-424) and soluble vascular endothelial growth factor receptor-1 (sFlt-1) mRNA expression on the levels of folate (FA) and vitamin B₁₂ (VitB₁₂) in pregnant women with fetal growth restriction (FGR).Methods The clinical data of 116 pregnant women with FGR (FGR group) and 116 pregnant women with normal fetus (control group) delivered in our hospital from January 2017 to January 2019 were retrospectively analyzed. Comparing the fetal growth parameters [body weight at birth, length, abdominal circumference, head circumference, body mass index(BMI)], serum miR-424, sFlt-1 mRNA, FA, VitB₁₂ between the two groups. Pearson was used to analyze the correlation between serum indexes and fetal growth parameters and the correlation between serum miR-424 and sFlt-1 mRNA expression and FA and VitB₁₂. Receiver operating characteristic curve(ROC) and area under ROC(AUC) were used to analyze serum indexes to predict the efficacy of FGR.Results The body weight, length, abdominal circumference, head circumference, and BMI of the fetus at birth in the FGR group were lower than those in the control group(P <0.05); miR-424 and sFlt-1 mRNA in FGR group were higher than those in control group, FA and VitB₁₂ were lower than control group(P <0.05); miR-424 was negatively correlated with the body weight, body length, abdominal circumference, head circumference, and BMI of the fetus at birth(P <0.05); sFlt-1 mRNA was negatively correlated with body weight, body length, abdominal circumference, head circumference, and BMI of the fetus at birth(P <0.05); FA and VitB₁₂ was positively correlated with fetal body weight, body length, abdominal circumference, head circumference, and BMI at birth (P <0.05). The AUC of FGR predicted by miR-424 was 0.790; when the cutoff value was > 0.18, the sensitivity was 74.14%(95% CI: 0.476, 0.790), and the specificity was 71.55%(95% CI: 0.378, 0.800). The AUC predicted by sFlt-1 mRNA for FGR was 0.777; when the cutoff value was >6.39, the sensitivity was 56.03%(95% CI: 0.448, 0.664), and the specificity was 91.38%(95% CI: 0.207, 0.985). The AUC of FGR predicted by FA was 0.826；when the cut-off value was ≤11.24 μg/L, the sensitivity was 85.34% (95% CI: 0.576, 0.892), and the specificity was 66.38%(95% CI: 0.500, 0.716). The AUC of FGR predicted by VitB₁₂ was 0.831; when the cutoff value was ≤ 255.24 ng/L, the sensitivity was 85.34% (95% CI: 0.322, 0.948), and the specificity was 67.24% (95% CI: 0.517, 0.802). The AUC of combined indexes to predict FGR was 0.909, the sensitivity was 85.34% (95% CI: 0.672, 0.957), and the specificity was 82.76% (95% CI: 0.767, 0.906) (P < 0.05). Serum miR-424 and sFlt-1 mRNA were negatively correlated with FA and VitB₁₂ (P <0.05).Conclusion Serum miR-424 and sFlt-1 mRNA of FGR pregnant women are highly expressed, and can negatively regulate fetal growth and development by affecting the levels of FA and VitB₁₂. Detecting the expression of various indicators is expected to become a serological method for predicting FGR.