孕妇生化代谢指标与胎儿神经管畸形的相关研究

Correlation study of biochemical metabolic indexes of pregnant women and fetal neural tube defects

目的了解母体叶酸、维生素B12与胎儿神经管畸形发生的相关性，为预防和治疗胎儿神经管畸形提供科学依据。方法选择山西省神经管畸形高发地区的孕妇作为本次研究的对象，其中孕12～20周B超诊断为神经管畸形（NTDs）的孕妇52例为病例组，孕12～20周因各种原因需要终止妊娠进行引产，经病理解剖证明胎儿正常的52例患者为对照组。对两组孕妇进行问卷调查，检测两组孕妇血清叶酸、维生素B12、总同型半胱氨酸（tHcy）、S-腺苷甲硫氨酸（SAM）、S-腺苷同型半胱氨酸（SAH）、DNA甲基化指数水平及比较其对神经管畸形的诊断价值，并比较病例组及对照组的差异性。结果孕妇血清叶酸〈7．6nmol／L、维生素B12〈169pmol／L、tHcy≥11．3umol／L，SAM〈49nmol／L，SAH≥11nmol／L，DNA甲基化指数〈4．4是神经管畸形的危险因素（OR值分别为：5．95、3．20、2．56、11．11、479．40和625，均P〈0．05）。DNA甲基化指数诊断神经管畸形的ROC曲线下面积及约登指数最大。两组孕妇血清叶酸、维生素B12、同型半胱氨酸、一碳基团中间代谢物、DNA甲基化指数均有显著差异性（均P〈0．05）。结论叶酸、维生素B12缺乏可能通过改变母体一碳基团代谢水平影响胎儿DNA甲基化，最终导致神经管畸形的彤成。DNA甲基化指教诊断神经管畸形的价值最高。

Objective To understand the correlation between maternal folic acid and Vitamin B12 with the incidence of fetal neural tube defects （NTDs） , so as to provide scientific basis for prevention and diagnosis of NTDs. Methods Pregnant women in areas of Shanxi Province with high incidence of NTDs were selected. The case group included 52 pregnant women at 12-20 gestational weeks diagnosed with NTDs by B-ultrasonography, and the control group recruited 52 pregnant women at 12-20 gestational weeks undergoing induced abortion due to various reasons, whose fetuses were confirmed to be normal by pathological anatomy. Questionnaire survey was conducted on two groups. The levels of folic acid, Vitamin B12, total homocysteic acid （tHcy） , S-adenosyl methionine （SAM） , S-adenosyl homocysteine （SAH） , index of DNA methylation of two groups were measured and their diagnostic values in diagnosis of NTDs were compared, The differences between two groups were analyzed. Results The risk factors of NTDs included folic acid 〈 7.6 nmol/L, Vitamin B12 〈 169 pmol/L, tHcy acuity ≥ 11.3 umol/L, SAM 〈 49 nmol/L, SAH≥ 1 l nmol/L, and DNA methylation index 〈 4.4 （OR value was 5.95, 3.20, 2.56, 11.11, 479.40 and 625, respectively, all P 〈 0.05 ）. When diagnosing NTDs with DNA methylation index, the area under ROV curve and Youden index were biggest. Two groups were significantly different in maternal folio acid, Vitamin B12, homocysteic acid, one carbon group intermediate metabolites, and DNA methylation index （P 〈 0.05 ）. Conclusion Deficiency of folic acid and Vitamin B12 may affect fetal DNA methylation by changing one carbon group metabolic level, and ultimately induce the formation of NTDs. DNA methylation index has the highest valoe in diagnosis of NTDs.