经皮脐静脉穿刺取材进行产前诊断的指征构成变化

Indications of percutaneous umbilical cord blood sampling in prenatal diagnosis

目的评估现有产前筛查诊断体系中,经皮脐静脉穿刺(percutaneous umbilical cord blood sampling,PUBS)的应用指征变化趋势及安全性,探讨减少不必要PUBS的可能性。方法回顾性收集2015年1月至2017年12月在北京大学第一医院通过PUBS取材行产前诊断的病例。分析PUBS指征、取材孕周、后续检测项目(胎儿淋巴细胞染色体核型分析、分子遗传学检测、病原学检查)、检测结果以及妊娠结局。采用单因素方差分析、R×C列联表χ2检验、Fisher精确概率法、线性趋势χ2检验或独立样本Cruskal-Wallis秩和检验,对数据进行分析。结果(1)研究期间共412例单胎PUBS病例,穿刺孕周为孕20~38周,其中孕34周前取材379例(92.2%)。检测结果阳性共43例(10.4%)。1.5%(6/412)穿刺术后发生流产。2015与2016年各有1例出现体外细胞培养失败。(2)304例(73.8%)单一指征中,14例为早孕期已知指征[高龄(年龄>35岁)、曾生育染色体病患儿、夫妻一方为染色体异常携带者],2015和2017年单纯因高龄行PUBS的病例分别为4和1例,2016年无此指征病例。290例(70.4%)指征为中晚孕期所发现(筛查高风险、产前超声检查怀疑胎儿染色体异常及其他指征)。因双重指征行PUBS者(105例)所占比例呈现逐年增多趋势,但差异未见统计学意义。其中8例(7.6%)以高龄及筛查高风险作为指征,占总体的1.9%(8/412)。(3)中晚孕期超声提示异常作为指征者共363例(88.1%)。其中280例为单纯超声异常,比例为76.9%(280/363),呈现逐年下降趋势;其余83例合并高龄、不良孕产史及筛查高风险等其他指征(双重和三重指征分别为80和3例),所占比例为23.1%(83/363),显现逐年上升的趋势;但差异均未见有统计学意义。经分子诊断检出异常结果共18例,均见于超声异常指征。结论尽管PUBS并发症发生率较低,但存在风险,因单一指征进行PUBS的比例逐年下降。在产前筛查体系逐步健全及分子核型普遍应用的前提下,应避免出现早中孕期存在指征者延误取材时间。应用分子诊断,可减少中晚孕期对PUBS取材的依赖。合理规范应用PUBS,减少不必要的PUBS,存在改善空间。

Objective To investigate the tendency and safety of percutaneous umbilical cord blood sampling(PUBS)in prenatal screening and diagnosis,and the possibilities of avoiding unnecessary PUBS.Methods This was a retrospective study of pregnant women who underwent PUBS for prenatal diagnosis in Peking University First Hospital from January 2015 to December 2017.Clinical indications,timing of PUBS,further investigations(chromosome karyotype,molecular genetics and pathogen testing),results,and pregnancy outcomes were collected and analyzed.One-way analysis of variance(ANOVA),Chi-square test for linear trend,Fisher's exact probability test/Cochran-Armitage analysis and Cruskal-Wallis rank-sum test were used for statistical analysis.Results(1)A total of 412 singleton pregnancies underwent PUBS at 20-38 gestational weeks during the study period,and 379(92.2%)of them received PUBS before 34 gestational weeks.The positive test results accounted for 10.4%(43/412).There were six(1.5%)miscarriages after PUBS.In vitro cell culture failure occurred in two cases,one in 2015 and the other in 2016.(2)Among the 412 cases,304(73.8%)had only one indication.Fourteen cases could be identified as high risk in the first trimester,such as advanced maternal age(AMA,>35 years),pregnant history with chromosomal abnormal fetus and one of the couples carrying abnormal genes.There were four,zero and one case receiving PUBS only for AMA in 2015,2016 and 2017,respectively.Indications,including high risk suggested by serum screening and fetal abnormality found by ultrasound were identified in 290 cases(70.4%)in the second or third trimester.Other than AMA,there were no statistically significant differences in single indicators.The proportion PUBS with double indicators increased from 2015 to 2017 but without significant difference.AMA and positive serum screening as indicators of aneuploidy screening accounted for 7.6%(8/105)in double-indicator group and 1.9%(8/412)in all.(3)There were 363 PUBS(88.1%)performed for ultrasound abnormalities.Among them,76.9%(280/363)only had abnormal ultrasound findings,and the percentage was decreased year by year.The other 83 cases(80 with double indicators and three with triple indicators)also presented with other indicators,including AMA,adverse pregnancy history and positive serum screening.The proportion of PUBS performed with the presence of multiple indicators tended to increase recently,but no statistically significant difference was found.All the 18 cases with abnormality diagnosed by molecular genetic testing had abnormal ultrasound findings.Conclusions Although PUBS's complications are rare,it carries some risks.The constitution of single indication has been declined every year.With the improvement of prenatal screening system and application of molecular karyotyping,the necessity of invasive prenatal diagnosis with PUBS is greatly reduced.An improvement in reasonable and standardized application of PUBS needs to be achieved.