Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Two factors affecting the success rate of the second non-invasive prenatal screening after initial no-call result: experience from a single tertiary center in China

Background:One inevitable shortcoming of non-invasive prenatal screening(NIPS)/cell-free DNA(cfDNA)sequencing is the uninterpretable(“no-call”)result,which is mainly caused by an insufficient fetal fraction.This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results.Methods:We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center.We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time.Results:Among the 33,684 women who underwent NIPS,137 with a no-call result underwent a retest.Comparison between the 87(63.50%)women with a successful retest and the other 50(36.50%)women showed a significant difference in both the initial fetal fraction and maternal body mass index(BMI),whereas the other factors showed no significant differences.In addition,with an initial fetal fraction of<2.00%,the retest success rate was very limited.Conclusions:We identified two major factors associated with a successful NIPS retest:the initial fetal fraction and the maternal BMI.These findings suggest the need for specialized management for this subset of women and would be instructional for the counseling for these women.

Role of different examination methods in colorectal cancer screening:Insights and future directions

Colorectal cancer is a malignant tumor with the third and second highest incidence and mortality rates worldwide,and its mortality rate is increasing annually.Colorectal cancer evolves gradually over a long period of time.The evolving process from colorectal adenoma to colorectal cancer takes approximately 10-15 years,providing a sufficiently long"window period"for early screening and diagnosis of colorectal cancer.The recurrence and mortality rates can be controlled at a low level with an early intervention.Metaxas et al summarized existing screening methods and their applicable scope in a recent publication.Moreover,they provide suggestions on how to improve adherence.This editorial provides a commentary on their article and discuss the roles of different screening methods in the early screening of colorectal cancer.

Validity of Different Methods to Prenatal Screening for Down’s Syndrom During First and Second Trimester Pregnancy of Chinese Women

Objective To identify and determine the optimal method to screening for fetal Down＇s syndrome （DS）. Methods Three large cohorts with 17 118, 39 903, 16 646 subjects were enrolled for the first trimester double marker （pregnancy-associated plasma protein A and free [B-human chorionic gonadotropin） screening （FTDMS）, second trimester double marker （c{-fetoprotein and free B-human chorionic gonadotropin） screening （STDMS）, and second trimester triple marker （a-fetoprotein, free 13-human chorionic gonadotropin and unconjugated estriol 3） screening （STTMS）, respectively. The sensitivity, specificity, false positive rate （FPR）, false negative rate （FNR） and the areas under ROC curves （AUCs） were estimated in order to determine the optimal screening method in women under or above 35 years old. Results For women under 35 years old, STTMS was the best method with a detection rate of 68.8% and FPR of 4.3% followed by the STDMS with a detection rate （sensitivity） of 66.7% and FPR of 4.9%. The FTDMS had a lower detection rate of 61.1% and FPR of 6.3%. For women above 35 years old, the detection rate of all the methods was similar, but STTMS method had a lowest FPR of 15.9%. For women under 35 years old AUCs were 0.77 （95% CI, 0.64 to 0.91）, 0.81 （95% CI, 0.71 to 0.91）, and 0.82 （95% CI, 0.69 to 0.96） for FTDMS, STDMS, and STTMS methods, respectively; for those above 35 years old, AUCs were 0.70 （95% CI, 0.56 to 0.83）, 0.70 （95% CI, 0.59 to 0.82）, 0.78 （95% Cl, 0.58 to 0.97） for FTDMS, STDMS and SITMS, respectively. Conclusion Findings from our study revealed that STDMS is optimal for the detection of fetal DS in pregnant women aged under 35. For individual women, if economic condition permits, STFMS is the best choice, while for women aged above 35, STTMS is the best choice in this regard.

Non-invasive Prenatal Diagnosis of Trisomy 21 by Dosage Ratio of Fetal Chromosome-specific Epigenetic Markers in Maternal Plasma

This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Maternal plasma samples were collected from 388 singleton pregnancies, and placental or chorionic villus tissues from 112 of them. Methylation-specific PCR （MSP） and methylation-sensitive restriction enzyme digestion followed by fluorescent quantitative PCR （MSRE ＋ PCR） were employed to detect the maternal-fetal methylation difference in AIRE and RASSF1A. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. Moreover, the differential methylation for each locus could be seen during the whole pregnant period. The positive rates of fetal AIRE and RASSF1A in maternal plasma were found to be 78.1% and 82.1% by MSP and 94.8% and 96.9% by MSRE ＋ PCR. MSRE ＋ PCR was superior to MSP in the identification of fetal-specific hypermethylated sequences （P〈0.05）. Based on the data from 266 euploidy pregnancies, the 95% reference interval of the fetal AIRE/RASSF1A ratio in maternal plasma was 0.33-1.77, which was taken as the reference value for determining the numbers of fetal chromosome 21 in 102 pregnancies. The accu-racy rate in 98 euploidy pregnancies was 96.9% （95/98）. Three of the four trisomy 21 pregnancies were confirmed with this method. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.

Enrichment of Fetal Nucleated Red Blood Cells by Multi-core Magnetic Composite Particles for Non-invasive Prenatal Diagnosis

A novel kind of multi-core magnetic composite particles, the surfaces of which were respectively mo- dified with goat-anti-mouse IgG and antitransferrin receptor（anti-CD71）, was prepared. The fetal nucleated red blood cells（FNRBCs） in the peripheral blood of a gravida were rapidly and effectively enriched and separated by the mo- dified multi-core magnetic composite particles in an external magnetic field. The obtained FNRBCs were used for the identification of the fetal sex by means of fluorescence in situ hybridization（FISH） technique. The results demonstrate that the multi-core magnetic composite particles meet the requirements for the enrichment and speration of FNRBCs with a low concentration and the accuracy of detetion for the diagnosis of fetal sex reached to 95%. Moreover, the obtained FNRBCs were applied to the non-invasive diagnosis of Down syndrome and chromosome 3p21 was de- tected. The above facts indicate that the novel multi-core magnetic composite particles-based method is simple, relia- ble and cost-effective and has opened up vast vistas for the potential application in clinic non-invasive prenatal diag- nosis.

Non-invasive Prenatal Gene Diagnosis: Progress through Cell-free Fetal DNA and RNA in Maternal Plasma and Urine

Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also prevent tangential illness in fetuses and thus, reduce the incidence of diseases. Moreover, it is non-invasive prenatal gene diagnosis that prevents potential threaten and danger to both mothers and fetuses. Therefore, it is welcomed by clinical gynecologist and obstetrian, researchers of medical genetics, and especially, pregnancies. This review article touches briefly on the advanced development of using cell-free DNA, RNA in maternal plasma and urine for non-invasive prenatal gene diagnosis.

Discrepancy between non-invasive prenatal testing result and fetal karyotype caused by rare confined placental mosaicism: A case report

BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,who obtained a false-positive result on NIPT with a high risk for trisomy 21.Copy-number variation sequencing on amniotic fluid cells,fetal tissue,and placental biopsies showed that the fetal karyotype was 47,XXY,while the placenta was a rare mosaic of 47,XY,+21;47,XXY;and 46,XY.CONCLUSION The patient had a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,which caused a discrepancy between the result of NIPT and the actual fetal karyotype.It is important to remember that NIPT is a screening test,not a diagnostic test.Any positive result should be confirmed with invasive testing,and routine ultrasound examination is still necessary after a negative result.

Comparison of next generation sequencing-based and methylated DNA immunoprecipitation-based approaches for fetal aneuploidy non-invasive prenatal testing

Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.

Biomarkers for detecting colorectal cancer non-invasively: DNA,RNA or proteins?

Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.

A perspective study and financial analysis of different protocols of second trimester maternal serum screening for Down's syndrome

Objective:To compare the efficiency and related financial parameters of the double- and triple-marker test for the second-trimester maternal serum screening for Down's syndrome. Methods:The serum samples were collected from the 2^(nd) trimester pregnant women in this hospital and were examined for three biomedical markers[alpha-fetoprotein(AFP),freeβ-human chorionic gonadotropin(freeβ-hCG) and unconjugated estriol(uE_3)]by TR-FIA.The pregnancy outcomes were followed up and screening efficiency calculated for double-marker(AFP+freeβ-hCG) and triple-marker(AFP+ freeβ-hCG+uE_3) test. Results:(1)A total of 4,707 serum samples of 2^(nd) trimester pregnancy were collected in this study,of which 4,245 pregnancy outcomes got followed up by May 30,2009,with 462 cases lost to follow-up.The follow-up rate was 90.2%.3 cases of Down's syndrome,4 cases of other chromosome abnormalities and 1 case of neural tube defect (NTD) were found.There was no medically induced miscarriage by invasive tests.(2) Detection rate and false positive rate of triple marker test for Down's syndrome screening were 66.7%and 5.26%,respectively,while those in double marker test were 33.3%and 4.01%,respectively.The detection rate of all chromosome abnormalities was 75%in triple marker test and 37.5%in double marker test.The detection rate of NTD was 100%either in double or triple marker test.(3) It costs 499,375 RMB to avoid one Down's syndrome birth by using triple marker test and 781,200 RMB by using double marker test. Conclusion:Triple-marker test is superior to double marker test in 2nd trimester maternal serum screening for Down's syndrome,and costs less to avoid a Down's syndrome birth.

Application of intelligent algorithms in Down syndrome screening during second trimester pregnancy

BACKGROUND Down syndrome(DS)is one of the most common chromosomal aneuploidy diseases.Prenatal screening and diagnostic tests can aid the early diagnosis,appropriate management of these fetuses,and give parents an informed choice about whether or not to terminate a pregnancy.In recent years,investigations have been conducted to achieve a high detection rate(DR)and reduce the false positive rate(FPR).Hospitals have accumulated large numbers of screened cases.However,artificial intelligence methods are rarely used in the risk assessment of prenatal screening for DS.AIM To use a support vector machine algorithm,classification and regression tree algorithm,and AdaBoost algorithm in machine learning for modeling and analysis of prenatal DS screening.METHODS The dataset was from the Center for Prenatal Diagnosis at the First Hospital of Jilin University.We designed and developed intelligent algorithms based on the synthetic minority over-sampling technique(SMOTE)-Tomek and adaptive synthetic sampling over-sampling techniques to preprocess the dataset of prenatal screening information.The machine learning model was then established.Finally,the feasibility of artificial intelligence algorithms in DS screening evaluation is discussed.RESULTS The database contained 31 DS diagnosed cases,accounting for 0.03%of all patients.The dataset showed a large difference between the numbers of DS affected and non-affected cases.A combination of over-sampling and undersampling techniques can greatly increase the performance of the algorithm at processing non-balanced datasets.As the number of iterations increases,the combination of the classification and regression tree algorithm and the SMOTETomek over-sampling technique can obtain a high DR while keeping the FPR to a minimum.CONCLUSION The support vector machine algorithm and the classification and regression tree algorithm achieved good results on the DS screening dataset.When the T21 risk cutoff value was set to 270,machine learning methods had a higher DR and a lower FPR than statistical methods.

无创产前检测:迈向下一个十年

无创产前基因检测(NIPT)是过去10余年来产前筛查领域的重大突破,是围产医学领域的引领技术。通过低深度全基因组测序分析孕妇外周血胎儿游离DNA(cffDNA),实现了高效的唐氏综合征产前筛查,同时可扩展应用于其他染色体非整倍体、拷贝数变异等常见胎儿基因组问题的筛查,实现胎儿疾病的早期无创检测。但是,NIPT依然需要更多循证医学证据支持,以迈向更为广阔的应用空间。文章从NIPT适应证选择、NIPT异常结果分析、NIPT结果报道与解读中的伦理学问题、NIPT在胎儿基因变异筛查中的应用以及非cffDNA来源NIPT技术开发等角度,探讨了NIPT目前面临的问题与未来的发展趋势。

超声检查联合NIPT在高龄孕妇产前筛查中的应用价值

目的探讨超声检查联合无创产前DNA检测(NIPT)在高龄孕妇中对胎儿染色体异常筛查的临床应用价值。方法选取2020-2023年在宝鸡市妇幼保健院接受产前检查的3820例高龄孕妇作为研究对象,所有孕妇均接受超声检查及NIPT,以羊膜腔穿刺结果或妊娠结局作为胎儿染色体异常的诊断标准,比较超声检查、NIPT及二者联合应用对胎儿染色体异常的诊断情况。结果3820例高龄孕妇中NIPT筛查出高风险57例;超声检查软指标异常95例,结构异常63例;超声检查联合NIPT诊断胎儿染色体异常的灵敏度、特异度和阳性预测值分别为93.18%、99.89%、91.11%。结论高龄孕妇胎儿染色体产前筛查中,超声检查联合NIPT可以相互补充参考,可有效提高染色体异常检出的灵敏度、特异度,降低假阳性率和假阴性率,实现对出生缺陷的早发现、早诊断及早干预。

884例性染色体异常胎儿产前诊断结果分析

目的 对884例无创产前筛查(NIPS)提示性染色体异常的羊水样本进行核型分析、荧光原位杂交技术(FISH)和拷贝数变异测序(CNV-seq)检测,探讨不同方法在产前诊断中的价值。方法 选取2015年1月—2022年12月天津市中心妇产科医院孕早期NIPS提示胎儿为性染色体异常的孕妇884例,于孕中期采集羊水样本,进行羊水细胞核型分析和FISH检测,对结果不一致或培养失败的样本进一步行CNV-seq检测。结果 884例孕妇中,有341例(38.6%)检出异常核型,11例(1.2%)羊水细胞培养失败。NIPS性染色体阳性预测值为39.2%(341/873)。341例核型分析异常样本中,最常见的核型异常类型是47,XXY(108例),其次为47,XXX(80例)、47,XYY(68例)、45,X(18例),共检出51例嵌合体。884例孕妇中,有862例FISH检测结果与核型分析或CNV-seq结果一致,FISH的阳性预测值为97.5%;24例与核型分析结果不一致,进一步行CNV-seq检测,有22例CNV-seq结果与核型分析结果一致,并能相互补充分析;2例不一致样本中,1例核型分析结果为46,~+mar,FISH和CNV-seq结果均为45,X;1例核型分析结果为嵌合Y染色体异染色质区缺失,FISH和CNV-seq结果均为嵌合体,结构未见异常。结论 NIPS提示性染色体异常时,建议首选FISH和核型分析联合检测,可快速、准确地诊断染色体异常。对于疑似染色体特殊结构异常,建议进行FISH、核型分析和CNV-seq联合检测,可明确遗传学病因。

胎盘植入性疾病的早期识别及规范诊治

胎盘植入性疾病发病率日益升高,是全球性医疗核心问题,严重威胁着母婴健康。为了更好地管理胎盘植入性疾病,我们根据最新国际指南及循证医学证据,对其诊断标准、高危人群的早期识别、妊娠早、中晚期影像学筛查征象、分娩时机、手术方式做了详细的介绍。旨在早期识别及规范诊治胎盘植入性疾病,降低母儿并发症。

产前序贯性筛查遗传性耳聋基因携带者的临床意义分析

目的分析产前序贯性筛查遗传性耳聋基因携带者的临床意义。方法选择2022年5月至12月于首都医科大学附属北京妇产医院进行遗传性耳聋基因突变位点筛查的孕妇9391例,采用微流控芯片法检测遗传性耳聋基因,分析其在孕妇人群中的携带率。对检出GJB2基因和SLC26A4基因变异的孕妇配偶采用靶向高通量测序进行相同致病基因筛查,当夫妻双方均检出同一基因致病变异时建议对胎儿进行致病基因的产前诊断。对于检出GJB3基因变异孕妇,建议其进行听力学评估和遗传咨询及随访。对检出线粒体12S rRNA基因变异孕妇进行遗传咨询及用药指导。结果9391例孕妇中检出遗传性耳聋基因突变携带者1002例,携带率为10.67%;GJB2、SLC26A4、GJB3及线粒体12S rRNA突变的携带率分别为7.93%、1.99%、0.28%和0.15%。突变经Sanger测序验证,符合率达99.80%。293例GJB2基因或SLC26A4基因突变携带者的配偶进行了序贯性筛查,其中4对夫妇双方检出携带相同基因上的致病突变位点,经羊水细胞测序,1例为GJB2 c.235 del C纯合突变,1例为SLC26A4 c.919-2 A>G纯合突变,其余2例均为杂合突变。结论产前序贯性筛查耳聋基因携带者不仅可以筛查遗传性耳聋基因突变的携带者,还可以发现药物性耳聋敏感性个体,从而实现耳聋胎儿早期诊断、早期干预和及时预警。

甘肃地区育龄夫妇基因扩展性携带者筛查研究

目的:探讨甘肃地区育龄夫妇单基因遗传病携带情况,为对高危家庭进行遗传咨询与产前诊断提供依据。方法:回顾性分析2021年1月—2023年12月在甘肃省妇幼保健院就诊的887对育龄夫妇,采用目标区域捕获二代测序技术进行100种单基因隐性遗传病扩展性携带者筛查(expanded carrier screening,ECS)。有3个家系的母亲于妊娠18~21周抽取羊水15 mL进行产前基因诊断。结果:在887对育龄夫妇中检出31对高风险夫妇,其中25对常染色体隐性遗传病高风险夫妇,6对X连锁隐性遗传病高风险夫妇。在1774人(887对夫妻)中,678人为常染色体隐性遗传病携带者。高风险夫妇中GJB2基因携带率最高,其次为PAH基因与CFTR基因。有3对高风险夫妇妊娠期进行了产前诊断,1对夫妇因胎儿为囊性纤维化患儿选择了终止妊娠;另两对夫妇分别因胎儿为携带者和野生型表型选择继续妊娠,2例生后新生儿表型均正常。结论:育龄夫妇进行ECS有助于实施精准的产前诊断及生育指导,对降低出生缺陷有重要意义。

超声科医师对胎儿闭合性脊柱裂诊断标准的掌握现状及影响因素分析

目的探讨从事产前超声检查的超声科医师对胎儿闭合性脊柱裂诊断标准的掌握情况。方法2021年3月至2022年3月,在从事中孕期系统超声筛查工作的超声科医师中,发放关于胎儿闭合性脊柱裂产前筛查的调查问卷260份。初次问卷结束后,每周发放闭合性脊柱裂产前诊断及预后的相关资料,3个月后再次评估调查对象的掌握情况。统计学分析采用χ^(2)检验和二元Logistic回归分析。结果回收有效问卷237份,回收率91.2%(237/260)。单因素分析结果显示,年龄较大、从业年限较长、学历较高、有培训经历、检出过胎儿脊柱裂的超声科医师,对胎儿闭合性脊柱裂的掌握率较高(P值均<0.05)。二元Logistic回归模型分析结果显示,年龄、从业年限、学历、参与培训经历、检出过胎儿脊柱裂均为超声科医师掌握胎儿闭合性脊柱裂的影响因素(P值均<0.05)。相对于年龄<30岁者,30~<45岁(OR=4.351,95%CI:0.167~0.729)、≥45岁(OR=10.510,95%CI:0.225~0.823)的医师掌握程度更好;相对于从业年限<5年者,5~<10年(OR=4.624,95%CI:0.146~0.687)以及≥10年(OR=5.256,95%CI:0.224~0.895)的医师掌握程度更好;相对于本科以下学历者,本科(OR=2.424,95%CI:0.269~0.758)和本科以上(OR=5.819,95%CI:0.174~0.853)的医师掌握程度更好;相对于无培训经历者,有参与培训经历(OR=4.349,95%CI:0.294~0.801)的医师掌握程度更好;相对于未检出过胎儿脊柱裂者,检出过胎儿脊柱裂(OR=3.404,95%CI:0.182~0.836)的医师掌握程度更好。初次问卷调查中,超声科医师对闭合性脊柱裂的超声诊断标准掌握率为32.1%(76/237);培训3个月后,掌握率提高至88.6%(210/237)(χ^(2)=158.294,P<0.001)。结论从事产前超声检查工作的部分超声科医师未掌握胎儿闭合性脊柱裂的诊断标准,应加强专业培训和宣传推广。