Objectives This study aimed to investigate copy number variations (CNVs) and potential candidate genes associated with fetal congenital heart disease (CHD) and to compare the prevalence of CNVs among different CHD subtypes. Methods A retrospective analysis was performed on 391 fetuses diagnosed with CHD between 2019 and 2023. 391 fetuses with case were divided into three groups: isolated CHD (Group 1), complex CHD (Group 2), and CHD with extracardiac anomalies (Group 3). Amniocentesis was performed for all pregnant women, with both karyotyping and CMA conducted. Gene Ontology (GO) annotation and KEGG pathway analyses were conducted for isolated and complex CHD cases. Results CMA and karyotype detected total abnormalities in 22 % of all CHD fetuses, including a chromosomal aneuploidy rate of 7.2 %, a pathogenic CNV (pCNV) rate of 6.1 %. The overall detection rates for Groups 1, 2, and 3 were 11.6 %, 12.5 %, and 50 %, respectively. Group 3 exhibited significantly higher rates of chromosomal aneuploidy (23.7 %) and pCNV (17.8 %) compared to Groups 1 and 2 (p < 0.001 ). No significant differences in maternal age were observed among the three CHD groups. KEGG pathway analysis identified the top three enriched pathways for complex CHD were nucleocytoplasmic transport, cell adhesion molecules, and the mRNA surveillance pathway. Conclusions The rates of chromosomal aneuploidy and CNV abnormalities in CHD cases with extracardiac anomalies were significantly higher than in the other two groups. Maternal age was not associated with the chromosomal abnormalities observed in CHD cases. KEGG pathway analysis indicated more intricate molecular pathways in complex CHD.

Abstract Objective To evaluate the value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of high-risk pregnancies.Methods A total of 3459 pregnant women admitted to the Wuxi Maternal and Child Health Hospital between June 2020 and August 2022 were selected for this study. Both G-banding karyotype analysis and CMA were offered to all patients who underwent invasive prenatal diagnosis. Short tandem repeat (STR) analysis was performed to eliminate maternal contamination for interpretation.Results Chromosomal aberrations, including aneuploidies or triploid and mosaic aberrant karyotypes and copy number variants (CNVs) ≥ 5Mb, were detected by both G-banding karyotyping and CMA in 174 (5.0%) cases. A total of 326 (9.4%) cases with normal karyotypes were reported as CNVs in CMA, including 71 (2.1%) cases with pathogenic and likely pathogenic CNVs and 217(6.3%) cases with variants of uncertain significance (VOUS). On the other hand, 11 inversions, 23 balanced translocations, and 22 other chromosomal rearrangements were detected by karyotyping with normal CMA results.Conclusion The top 3 detection rates of different indications by CMA or karyotyping were 43.5% for NIPT high risk, 17.5% for abnormal ultrasound, and 17.7% for other indications. CMA is an effective diagnostic tool for high-risk pregnancies in perinatal medicine.

Background Chromosomal abnormalities are one of the common causes of birth defects,and karyotype analysis is still an important method for prenatal diagnosis of chromosomal abnormalities as well as an effective way to prevent and control birth defects.However,karyotype analysis,especially chromosomal image segmentation and classification mainly depends on manual work at present,which is laborious and time-consuming.As an emerging approach to karyotype analysis,it is of great significance to investigate the application value of artificial intelligence(AI)in prenatal chromosomal karyotype diagnosis.Objective To investigate the application effect and clinical value of AI in prenatal karyotype diagnosis.Methods A total of 1 000 pregnant women who received interventional prenatal diagnosis and karyotype analysis of amniotic fluid cells in the department of medical genetics and prenatal diagnosis of Wuxi Maternity and Child Health Care Hospital between 2020 and 2022 were selected as the study subjects.The karyotype analysis of all cases was performed using two-line mode,the results of the AI reading were reviewed by one geneticist in the first line,and another geneticist analyzed the karyotypes by Ikaros karyotype analysis workstation in the second line,the diagnostic results and time were recorded respectively.The final diagnosis of the samples were based on the manual review of the first line and the manual reading of the second line.Results Among the 1 000 amniotic fluid samples,735 cases were diagnosed as normal karyotype,233 cases as aneuploidy,0 case as structural abnormality and 32 cases as mosaicism by AI.The numbers of normal karyotype,aneuploidy,structural abnormality and mosaicism assessed by AI-assisted geneticist were 689,233,45 and 33,which were completely consistent with those evaluated by geneticist using Ikaros system.Compared with AI-assisted geneticist,AI-based diagnosis had strong consistency(Kappa=0.895,95%CI=0.866-0.924,P<0.01).The diagnostic accuracy,sensitivity and positive predictive value of AI-based diagnosis was 95.4%,95.4%and 100.0%,respectively,among which the normal karyotype,aneuploidy,structural abnormality and mosaicism were detected with a sensitivity of 100.0%,100.0%,0 and 97.0%,and the positive predictive value of 100.0%,100.0%,0 and 100.0%.The average diagnostic time of AI was shorter than that of AI-assisted geneticist and Ikaros-assisted geneticist(P<0.001),and AI-assisted geneticist took less time on average to diagnose than the Ikaros-assisted geneticist(P<0.001).Conclusion AI-assisted karyotype analysis of amniotic fluid cells has a high degree of automation,but its ability to recognize chromosomal structural abnormalities needs to be improved.It is suggested that AI be combined with the geneticist for karyotype analysis in clinical application to ensure the quality of prenatal diagnosis and improve efficiency.

Objective:To explore the clinical phenotypes, pregnancy outcomes, and follow-up of fetuses with 1q21.1 distal microdeletion/microduplication, and to provide a basis for prenatal and genetic counseling.Methods:This was a retrospective study involving 14 singleton fetuses with 1q21.1 distal microdeletion/microduplication that were prenatally diagnosed by karyotype analysis and chromosomal microarray analysis (CMA) at Wuxi Maternity and Child Health Care Hospital from January 2017 to June 2022. The results of ultrasound and genetic analysis, pregnancy outcome after genetic counseling, and postnatal follow-up were summarized using descriptive statistical methods.Results:All 14 fetuses had normal karyotypes. Out of the 14 cases, CMA indicated 1q21.1 distal microdeletion in eight cases and 1q21.1 distal microduplication in six cases. The fragments ranged from 813 kb to 4.48 Mb, all of which contained the key region of 1q21.1 microdeletion/microduplication syndrome and were pathogenic copy number variations (CNV). Among eight fetuses with distal 1q21.1 microdeletion, four cases had abnormal prenatal ultrasound findings, including one case with overlapping fingers of left hand and polyhydramnios, two were small for gestational age, and one with small head circumference. Among the six cases who underwent parental origin detection, the microdeletions were de novo in four fetuses and two fetuses were inherited from the parent with normal phenotype. As for six fetuses with distal 1q21.1 microduplication, nasal bone absence or hypoplasia was shown by ultrasound in four cases and no obvious abnormality was found in the other two cases. Parental origin detection was performed in four cases, which found that one case was de novo and the other three cases were inherited from their phenotypically normal parents. After genetic counseling, five families chose to terminate the pregnancies and the remaining nine cases continued the pregnancies to delivery. The last follow-up showed that all of the nine live births grew well, whose ages ranged from seven months to half past five years old. Conclusions:CMA is of great value in prenatal diagnosis of 1q21.1 distal microdeletion/ microduplication. Ones carrying pathogenic CNV may not develop the disease. Combined with ultrasound findings and parental genetic tracing results, individualized genetic counseling and long-term follow-up are of great importance for reasonable guidance in pregnancy outcome and reproduction.

Objective:To summarize the prenatal diagnosis and postnatal follow-up of 15q11.2 BP1-BP2 microdeletion syndrome (Burnside-Butler syndrome, BBS), and provide a reference for the management of BBS.Methods:A retrospective analysis was performed on 27 singleton pregnancies with fetal BBS that were prenatally diagnosed by single nucleotide polymorphism(SNP) array of amniotic fluid in Wuxi Maternity and Child Health Care Hospital from January 2017 to September 2021. Prenatal diagnosis indications, serological screening, prenatal ultrasound features, SNP array results, and postnatal growth and development were described and summarized.Results:(1) Of the 27 cases, the indications of prenatal diagnosis in 14 cases were abnormal sonographic findings, including eight cases with increased nuchal translucency, two with cleft lip and palate/alveolar process cleft, one with fetal multiple joint contracture syndrome, one with fetal right diaphragmatic hernia and single umbilical artery, one with suspected fetal duodenal atresia and one with nasal bone absence. Other indications included high risk of Down syndrome by serological screening in six cases, history of adverse pregnancy in six cases, and advanced age in one case. (2) Karyotyping of amniotic fluid in these 27 BBS fetuses showed normal results and SNP array indicated the deletion range of 311.8-855.3 kb. Parental verification of 23 cases confirmed one was a new mutation, seven were inherited from the father and 15 from the mother. (3) Five pregnancies were terminated in the second trimester and the remaining 22 cases were live births. (4) The median follow-up of the 22 children was 1 year 8 months (range 0.5 months to 4 years 3 months), which found low body weight and/or growth retardation in six cases, low body weight with language retardation in one case, low body weight with growth retardation and hyperactive behavior in one case, language retardation with left ear appendage in one case, cleft palate accompanied by duodenum/cleft lip and alveolar cleft in two cases without abnormal development after surgical treatment, and no abnormal growth in the remaining 11 cases.Conclusion:For BBS fetuses, the proportion of ultrasound abnormalities is high but with a low specificity in prenatal diagnosis, and the risk of abnormal postnatal growth and development/behavior is high, which requires continuous monitoring.

Objective:To investigate the ultrasonographic and genetic features of Cri-du-chat syndrome (CDCS).Methods:In this retrospective study, cases with CDCS diagnosed in Wuxi Maternal and Child Health Care Hospital from 2004 to 2021 and with complete data were reviewed to describe and analyze the maternal serum prenatal screening, non-invasive prenatal testing (NIPT), ultrasound, genetic examination data, and pregnancy outcomes.Results:All cases were diagnosed by karyotype analysis, seven of them were diagnosed prenatally through amniotic fluid, and four were diagnosed after birth through peripheral blood. Five of the seven cases diagnosed prenatally had an abnormal serological screening, including two cases with 5p- indicated by NIPT. Of the 11 cases, prenatal ultrasonography showed cerebellar transverse diameter less than －2 SD in eight cases, including four with cerebellar hypoplasia (CH), two with fetal growth restriction, and two with cranial diameters less than －2 SD. One case was shown with an increased nuchal translucency, accompanying bilateral choroid plexus cysts of the lateral ventricles, and suspected persistent left superior vena cava. No obvious ultrasound abnormality was observed in the remaining two cases. Among the seven cases diagnosed prenatally, excluding one case that refused parental verification, further single nucleotide polymorphism array (SNP array) showed that all six cases inherited the de novo mutations from the parents. The cytogenetic analysis found the breakpoints at 5p13, 5p14, and 5p15 in five, three, and three cases. All seven pregnancies were terminated in the second trimester. Four children diagnosed postnatally presented with CDCS phenotype during the follow-up at three years old. Conclusions:Fetal CDCS should be considered with CH detected by prenatal ultrasonography, though the correlation between CH and CDCS still needs further investigation. Gene mapping with an SNP array is helpful for phenotypic profiling and genetic counseling.

OBJECTIVE:To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.METHODS:Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.RESULTS:The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).CONCLUSION:The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.

OBJECTIVE:To assess the value of combined cytogenetic and molecular techniques for the prenatal diagnosis of a pregnant woman with intellectual disability (ID).METHODS:The fetus and its parents were subjected to G-banding karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis.RESULTS:G-banding karyotype analysis revealed that the woman has carried a chromosomal microdeletion 46,XX,del(11)(q24), and the fetus was a carrier of 46,XN,del(11)(q24)mat. Subsequent SNP-array and FISH analysis of the pregnant woman indicated that the microdeletion has mapped to 11q24.1-q25. Both the pregnant woman and her fetus were diagnosed with Jacobsen syndrome.CONCLUSION:Combined use of cytogenetic and molecular genetic techniques can facilitate diagnosis of patients with intellectual disability.

目的 确定FMR1基因CGG重复序列正常型、中间型和前突变型在无锡地区育龄妇女中的分布情况.方法 应用PCR技术对我院产前诊断中心育龄妇女(18～49岁)120例外周血样本进行FMR1基因的CGG重复序列进行检测.用GeneMapper 4.0软件分析毛细管电泳结果,用SPSS 11.0软件进行数据分析.结果 120例受检者中无前突变及全突变检出.共检测到2例灰区携带者,其余118例(CGG)n重复数范围为21 ～44,其中(CGG)n重复数为28和29的占所有受检者的最高.结论 本文为首次在无锡地区普通育龄期妇女开展的FMR1基因突变携带频率的研究,为今后筛查试验的可行性提供数据.

Objective To explore the screening efficiency about the first trimester screening of pregnancy-associated plasma protein A (PAPP-A)combined with the second trimester screening of alpha fetoprotein (AFP),free β-human cho-rionic gonadotropin (free β-HCG),uncojugated estriol (uE3)strategies for Down's Syndrome (DS)and Edwards' syn-drome (ES). Methods The clinical data from 7055 cases of pregnant women with pregnancy outcome,who underwent prenatal screening test,were retrospectively analyzed. The serum PAPP-A,free β-hCG in the first trimester,and AFP, free β-HCG,and uE3 in the second trimester were detected in all pregnant women. We designed three screening tests as three groups:projects A,B,and C. The risk evaluation of project A was serum free β-hCG and PAPP-A levels in the first trimester screening. Project B included free β-hCG,AFP,and uE3 levels in the second trimester. As for project C - so called the integrated serum test,included the serum PAPP-A levels in the first trimester,and AFP,β-hCG,and uE3 in the second trimester. The risks of DS and ES were evaluated by LifeCycle 4. 0 software based on the age,weight and gesta-tional week of gravidas. The cut-off value (high risk)and the intermediate risk value were > 1 / 270 and 1 / 1000 - 1 / 270 in DS,> 1 / 350 and 1 / 1000-1 / 350 in ES,respectively. We compared the high risk rate,intermediate risk rate in both DS and ES as well as the total positive rates among the three screening tests mentioned above. The women who terminated preg-nancy were identified by prenatal diagnosis via amniocentesis. Furthermore,those who did not terminate pregnancy were confirmed by the pregnancy outcomes,and were followed up based on karyotype of newborns. We evaluated screening effi-ciency of DS and ES such as the detection rate (DR)and false positive rate (FPR)among the three screening strategies. Results The high risk and the intermediate risk in DS as well as the screening positive rate of the project C were signifi-cant lower than those of projects A and B,respectively (P < 0. 05)(neural tube defect were excluded). A total of 9 fetus with true DS were diagnosed via amniocentesis and follow-up pregnancy outcomes. In the project A,the number of high risk was 7,DR and FPR for trisomy 21 was 77. 8% (7 / 9)and 3. 95% (279 / 7055),respectively. In the project B,the num-ber of high risk was 6,DR and FPR for trisomy 21 was 66. 7% (6 / 9)and 4. 24% (299 / 7055),respectively. In the project C,DR and FPR for trisomy 21 was 88. 9% (8 / 9)and 1. 80% (127 / 7055),respectively. The DR and FPR for DS in the project C were both superior to those in the projects A and B (DR:P > 0. 05,FPR:P < 0. 05). We diagnosed two fetus with true ES through amniocentesis and follow-up pregnancy outcomes. Only one case was successfully detected by all three screening projects. The other case was detected as high risk in the combined screening test. The detection rate for ES in the project C was higher than those in both projects A and B. Conclusion The screening efficiency about the first trimester screening of PAPP-A combined with the second trimester screening of AFP,free β-HCG,and uE3 for DS and ES is superior to both the first trimester double test (PAPP-A and free β-HCG)and the second trimester triple test including AFP,free β-HCG,and uE3.

The aim of this study was to examine the clinical and cytogenetic results of 4761 amniocentesis (AS) cases retrospectively in our clinic in southeast China. The prenatal diagnosis indications, detected chromosomal anomalies and the detection rate of chromosomal abnormalities were studied in 4761 patients who underwent AS between June 2014 and July 2016 retrospectively. Chromosomal abnormality was detected in 137 (2.88%) of the 4761 samples (89.1% numerical, 10.9% structural). The most frequent numerical chromosomal abnormality was trisomy 21 (59.0%). Clinically insignificant polymorphisms were the most frequent structural changes (n = 284). In our study, the frequency and proportion of abnormal karyotypes varied substantially across different maternal AS indications.Impact statementWhat is already known on this subject: Several studies on amniocentesis indications and results have been reported from China and from other countries. It has been known that the most common indications were the increased risk at maternal serum screenings (MSS) and advanced maternal age (AMA).What the results of this study add: In our study we make a conclusion that the indications and results of AS cases from our centre indicated the significance of genetic screening.What the implications are of these findings for clinical practice and/or further research: Our data could offer informative data for proper prenatal genetic counselling of pregnant women and their partners in Wuxi, China.

目的 联合应用染色体核型分析及芯片检测,对一例反复缺陷儿妊娠史有再生育需求夫妇进行产前诊断与遗传咨询,为有效预防出生缺陷提供诊疗思路.方法 夫妇双方及本次妊娠胎儿进行G显带染色体核型分析,采用微阵列比较基因组杂交(array-based comparative genomic hybridization,array-CG H)技术排除致病性染色体微缺失微重复.结果 丈夫核型为46,XY,t(5;6)(p13;p25),孕妇核型正常,胎儿染色体核型46,XN,结合第二胎猫叫综合征(Cri-du-Chat syndrome,CDCS)引产史,考虑为父源性CDCS;array-CGH检测未发现致病性拷贝数变异(Copy number variation,CNV);孕妇继续妊娠并顺产健康男婴,随访至今无异常.结论 细胞与分子遗传学方法相结合合理应用,可为反复缺陷儿妊娠史夫妇查找病因,减少再发风险,改善妊娠结局,达到优生优育的目的.

OBJECTIVE:To determine the karyotype of a fetus with transverse aortic arch hypoplasia, and to investigate the feasibility of array-based comparative genomic hybridization (array-CGH) for molecular genetic diagnosis.METHODS:G-banding was performed to analyze the karyotypes of the fetus and its parents, and array-CGH was applied to identify the chromosomal abnormality of the fetus.RESULTS:G-banding analysis revealed that the pregnant woman has carried a balanced translocation 46,XX, t(8;16)(p21;q24), while the fetus has carried an unbalanced translocation 46,XX,der(16)t(8;16)(p21;q24)mat. Array-CGH analysis suggested that the derivative chromosomal fragment has originated from 8p with breakpoints in 8p23.3-p21.3.CONCLUSION:Trisomy 8p23.3-p21.3 may have predisposed to transverse aortic arch hypoplasia in the fetus. Parental karyotype analysis could help to characterize the translocation and evaluate the recurrent risk. Compared with routine karyotype analysis, aCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations.

Objective To study the value of nuchal translucency(NT)thickness and nasal bone(NB)ab-normal in diagnosis of fetal chromosomal abnormalities at first trimester of pregnancy.Method Crown rump length was measured between 45 ~84 mm in the center of the fetal sagittal section,then the thick-ness of nuchal translucency(NT)and the status of nasal bone were detected.Combined with maternal se-rological screening and the age of pregnant women,the risk of chromosomal abnormalities was evaluated, for high-risk cases,there was suggestion for amniocentesis.NT thickness and nasal bone abnormalities were evaluated in the value of screening fetal chromosomal abnormalities with the results of chromosome examination as comparison.Results The PPV of NT thickness for predicting fetal chromosomal abnor-mality was 15 .93%,for nasal bone(NB)absence,the PPV was 40.00%.Combined both of them to pre-dict fetal chromosomal abnormalities,the PPV was 55 .56%.P <0.05 ,the differences are statistically significant.Conclusions NT thickness and nasal bone dysplasia have higher relation with fetal chromo-somal abnormalities,there are important indicators for chromosome abnormalities in the first trimester. Combined NT and nasal bone,it can further improve the detection rate of fetal chromosomal abnormali-ties,and it has great value of fetal chromosomal abnormalities screening.

OBJECTIVE:To verify the diagnosis of Angelman syndrome(AS) in a proband in order to provide prenatal diagnosis for his family.METHODS:Array comparative genome hybridization(array-CGH) and fluorescence in situ hybridization(FISH) on metaphase chromosomes were performed.RESULTS:The karyotype of the proband was normal, and a regional deletion of 15q11.1-11.2 was detected by array-CGH. FISH analysis has confirmed loss of heterozygosity in 15q11.2. No positive results were obtained by array-CGH or karyotype analysis. Amniotic fluid sample was taken from the proband's mother upon her subsequent pregnancy. The karyotype of the fetus was normal, but SNP microarray chip analysis has identified loss of heterozygosity in 8p23.1-p22. As no abnormality was observed by ultrasound and other prenatal examinations, the pregnancy was recommended to continue to full-term, and a healthy infant was born.CONCLUSION:Clinically suspected AS can be diagnosed by array-CGH and FISH. The result may facilitate accurate genetic counseling and prenatal diagnosis for the affected family.

目的 分析181例羊水染色体异常的临床资料,探讨其遗传咨询与处理方式以合理指导妊娠结局.方法:2008年1月-2013年12月,无锡市妇幼保健院产前诊断中心对4 879例具有产前诊断指征孕妇行羊膜腔穿刺、羊水细胞培养、G显带核型分析.获得染色体报告后,予以遗传咨询,跟踪随访胎儿妊娠结局.结果 4 879例羊水细胞中,共检出异常核型181例,阳性检出率3.71％.异常核型中,各项高危指征所占比例分别为产前筛查高风险40.33％、高龄16.02％、夫妻一方染色体异常13.26％、超声软指标异常8.29％、无创高风险6.63％、不良孕产史4.42％、具有两项以上指征11.05％.异常核型的遗传咨询:①染色体数目异常尤其是常染色体数目异常的胎儿,建议终止妊娠;②嵌合体复查脐血验证,并结合临床、超声资料慎重给予建议;③来源不明的mar染色体,运用不同显带方式,必要时加做父母染色体,采用分子遗传方法探明来源后指导妊娠结局;④平衡易位、倒位携带者一般无异常表型但不排除少数特例,结合影像学检查情况,告知风险;⑤几例衍生染色体、环状染色体含有染色体的部分缺失、重复可产生异常表型,建议终止妊娠;⑥多态性变异一般影响不大,但应告知有生殖异常等风险.结论 ①产前诊断高危指征的孕妇,胎儿染色体异常率增加,应建议其行侵入性产前诊断;②羊水染色体核型异常的胎儿,根据不同情况,咨询医生的综合判断与个体化遗传咨询相结合、合理指导妊娠结局十分重要.

目的：探讨母体血清学筛查-产前超声筛查-染色体核型分析的序贯诊断模式在产前诊断三倍体胎儿中的应用价值。方法对2008年10月至2014年4月，无锡市妇幼保健院产前诊断中心确诊为三倍体综合征的5例患者的血清学指标、超声特征、染色体结果及临床表现进行综合分析。结果（1）母体血清学筛查：1例行妊娠早期唐氏综合征筛查，结果发现游离绒毛膜促性腺激素β亚单位（free beta subunit of human chorionic gonadotropin，free β-hCG）和妊娠相关血浆蛋白A均明显低于正常；4例行妊娠中期唐氏综合征筛查，结果free β-hCG和游离雌三醇也显著低于正常；5例患者均为18-三体高风险。（2）产前超声筛查：5例胎儿均呈不对称性胎儿生长受限、小胎盘、羊水偏少；体位均不同程度受限，脊柱异常弯曲，始终保持极度俯屈状态；合并并指畸形2例、单脐动脉2例、心脏畸形2例。（3）胎儿染色体核型分析：5例三倍体胎儿中1例为69,XXY，4例为69,XXX。结论三倍体胎儿母体血清学筛查、超声筛查均有特征性异常表现，提示需行核型分析明确诊断。序贯诊断模式对产前诊断中尽早确诊三倍体胎儿并进行临床干预具有重要价值。

Objective To investigate pregnancy outcome of women with abnormal increased HCG level and low risk of Down's syndrome in the mid trimester of pregnancy,to provide theoretical basis for clinical consultation about abnormal HCG in Down's screening. Methods 212 pregnant women with low risk of Down's syndrome through Down's screening in the mid trimester of pregnancy in Wuxi hospital for maternal and child health care affiliated to Nanjing medical university during October 2012 to December 2013,were selected as study subjects,among whom 112 cases with abnormal increased HCG level were included in test group,the other 100 cases with normal HCG level were included in control group. Their pregnancy outcome was followed up, and the abnormal pregnancy ( premature rupture of membranes, macrosomia, fetal anomaly and anomaly of placenta)of two groups of cases was analyzed. Results Prevalence of macrosomia,fetal anomaly and anomaly of placenta among cases in test group were significantly higher than those among cases in control group,respectively(P<0. 05). There was no significant difference in prevalence of premature rupture of membranes between two groups( P>0. 05 ) . Among 5 fetal anomaly cases in test group,3 cases had cardiac abnormalitis,1 case had lung cystadenoma,1 case had suspected Down's syndrome by noninvasive gene screening,and Down's syndrome was proved by amniocentesis,then the case underwent odinopoeia. Among 9 cases with placental abnormality,6 cases had placental adherence,2 cases had placenta morphologic abnormality,and 1 case had placental abruption. Conclusion Abnormal increased HCG level in the mid trimester of pregnancy is related to adverse pregnancy outcomes such as macrosomia,fetal anomaly and anomaly of placenta.

孕妇 27岁．因“三胎一产，停经25同，羊水偏多1周”来院就诊。夫妻二人体格、智力发育正常．非近亲结婚．孕期无不良因素接触史。首次妊娠孕37＋3周时因“胎儿宫内窘迫”剖宫产一男婴，出现新生儿呼吸窘迫综合征、病理性黄疸、多脏器水肿等系列表现（高度疑诊Beckwidl—Wiedernann综合征），

ObjectiveTo investigate the effects of isotope labeled folate targeting albumin nanoparticles(188Re-fo late-CDDP/HAS MNP) on human SKOV3 ovarian cancer cells in vivo.MethodsThe human SKOV3 ovarian cancer model was established in mice.Sixty-four tumor-bearing mice were randomly divided into eight groups:(A) negative control group,(B) chemotherapy group,(C) radiotherapy alone group,(D) hyperthermia alone group,(E) chemotherapy combined with radio therapy group,(F) chemotherapy combined with hyperthermia therapy group,(G) radiotherapy combined with hyperthermia therapy group and(H) hyperthermia,chemotherapy and radiotherapy combined treatment group.After treatment,the cell pro liferation and tumor growth were observed.The inhibitory rate of tumor mass was measured.The histopathological changes of tumor were observed in all groups.ResultsThe quality of tumor was significantly lower in treatment groups than that of control group(P < 0.05).There was the lowest quality of tumor in hyperthermia,chemotherapy and radiotherapy combined treatment group than that of other treatment groups(P < 0.05).ConclusionThe combination of magnetic induction hyper thermia,chemotherapy,targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer,which has the potential application for ovarian cancer treatment.