宁波地区非叶酸因素致胎儿神经管畸形(NTDs)的研究

A study on fetal neural tube malformations(NTDs) caused by non-folic acid factors in Ningbo

目的 探讨非叶酸因素如孕妇年龄、单双胎、生态环境、遗传基因、胎儿性别等对胎儿形成神经管畸形的影响。方法 使用B超对高危孕妇(筛查阳性、高龄)进行产前超声诊断以明确是否有神经管畸形,对确诊为神经管畸形行流产手术后的胎儿组织经知情同意后取样并进行基因芯片检测。结果 诊断为NTDs的35岁以下孕妇占0.06%,35岁以上孕妇占0.11%,双胎为NTDs的比率是单胎的2.5倍,有统计学差异,孕妇来自生态环境指数较低的镇海等工业区占比80%,来自生态环境指数较高的象山仅有1例,基因芯片有24例正常,10例致病性异常包括了染色体微缺失、微重复导致的一些综合征,胎儿性别男女比例约为53∶47,符合正常出生性别比例。结论 年龄35岁以上的高龄孕妇生育NTDs胎儿的比例约为35岁以下孕妇的2倍,双胎妊娠患NTDs的风险是单胎妊娠的2.5倍,生态环境指数较高的地区如象山患NTDs的风险较工业区要低得多,提示生活在环境好的地区有可能可以降低NTDs的风险,染色体的微缺失及微重复是导致一部分NTDs产生的一个重要原因,但还不能完全排除叶酸相关代谢的影响,胎儿性别对NTDs产生没有明显影响。

Objective To explore the effects of non-folic acid factors such as maternal age, single/twins, ecological environment, genetic genes, fetal gender, etc. on the formation of neural tube malformations in fetuses. Methods Ultrasound was used for prenatal diagnosis of high risk pregnant women(screening positive, elderly) to determine whether the neural tube defects existed or not. The fetal tissue taken from the abortion operations which diagnosed with neural tube defects were agreed with the informed consent and the CMA testing were also conducted. Results Pregnant under the age of 35 diagnosed with NTDs accounted for 0.06% while those over the age of 35 accounted for 0.11%, and the ratio of twins with NTDs was 2.5 times that of singletons. There was a statistical difference in the ratio. Pregnant from industrial areas such as Zhenhai with low ecological environment index accounted for 80%, and those from Xiangshan with high ecological environment index only harbor 1 case. Additionally, 24 cases CMA results were normal and 10 cases with pathogenic abnormalities, including some syndromes caused by chromosome microdeletion and microduplication. The gender ratio of fetus is about 53∶47, which is in line with the normal gender ratio of birth. Conclusion The proportion of pregnant over the age of 35 giving birth to NTDs fetuses is about twice that of pregnant under the age of 35. The risk of NTDs in twin pregnancy is 2.5 times that of singleton pregnancy. The risk of NTDs in areas with high ecological environment index, such as Xiangshan, is much lower than that in industrial areas, suggesting that living in areas with better environment may reduce the risk of NTDs. Chromosome microdeletion and microduplication are important causes for the formation of some NTDs. However, the effects of folic acid related metabolism cannot be completely excluded, and fetal gender has no significant effects on NTDs.