孕早期产前筛查在染色体异常胎儿诊断中的应用

目的 评价孕早期产前筛查在降低染色体异常胎儿出生率中的应用价值.方法 采用时间分辨荧光免疫技术对2 806例单胎孕妇外周血妊娠相关蛋白-A (PAPP-A)和游离人绒毛膜促性腺激素β亚基(β-HCG)含量进行检测,综合超声测量胎儿颈项透明膜厚度(NT)及孕妇年龄、体质量和孕周,用LifeCycle3.0软件计算出胎儿患21-三体和18-三体的风险率,高风险孕妇经绒毛或羊水细胞染色体核型分析确诊.结果 在2 806例孕妇中共筛查出高风险孕妇115例,阳性率为4.1％,其中83例高风险孕妇经绒毛或羊水细胞染色体核型分析发现异常核型14例,异常发生率为16.9％,其中包括6例21-三体,1例21-三体嵌合体,3例18-三体,2例Turner综合征,1例三倍体和1例染色体结构异常核型.结论 孕早期产前筛查可以有效筛查出染色体异常胎儿.     

侵入性产前诊断指征与染色体核型检出结果的对比分析

目的探讨侵入性产前诊断指征选择对胎儿染色体异常核型检测的意义。方法对我院2004-07～2009-09间1 133例因妊娠中期孕母血清学筛查高危、孕母年龄≥35岁、超声筛查或检查异常、不良孕产史(包括自然流产史、死胎死产、胎儿畸形、出生缺陷)等不同指征的孕妇进行侵入性产前诊断,取材羊水或脐带血,经培养成功后进行染色体核型分析,指征分单一指征及复合指征。结果全部病例中共检出异常核型38例(3.35%)。在单一的指征中,超声测量胎儿NT值增高、母高龄、母血清学筛查高危的常染色体三体(包括21+三体、18-三体)检出率分别为5.0%、1.62%和0.49%;总的异常核型检出率最高为生育畸形儿或畸胎史11.76%,其次为胎儿B超异常6.9%,自然流产史5.9%。而复合指征中,高龄+NT值增高的常染色体三体检出率为14.29%;高龄+胎儿B超异常的常染色体三体检出率为5.88%;总异常核型检出率为17.65%。结论对高龄孕妇直接进行产前诊断,仍是一条检测出胎儿常染色体三体综合征的主要途径。关注超声检测胎儿NT值增高、胎儿异常以及有不良孕产史孕妇,尽可能地在孕期检出患有染色体疾病的胎儿,降低出生缺陷。     

超声检测胎儿颈背皮肤透明带厚度在产前筛查21-三体综合征的研究

目的 探讨超声测量胎儿颈背皮肤透明带厚度(nuchalskinfold thickness,NT)在染色体异常疾病21-三体综合征筛查的应用价值.方法 经腹超声测量孕12～27周孕妇1500例胎儿颈背皮肤透明带厚度,并与染色体核型分析及随访后结果作对照.结果 1 500例胎儿中,21-三体综合征的发病率为3.3‰,其中NT增厚者有62例,其中4例为21-三体综合征;无NT增厚中,有1例21-三体综合征.敏感性为80%,特异性为96.07%,准确性为96.12%,阳性预测值为6.45%.结论 NT检测对于21-三体综合征的早期诊断具有重要的意义,是早中期妊娠阶段产前筛查有效可行的方法.     

沈阳地区962例孕妇羊水细胞染色体异常产前诊断的分析

目的分析在羊水中染色体异常核型与产前诊断指征的关系。方法回顾性分析该院产前诊断中心2012-01~2012-12共962例孕妇的羊水穿刺产前诊断指征和染色体异常结果资料。结果羊水染色体培养成功率99.7%。发现异常核型45例(4.6%),其中常染色体三体(13-三体、18-三体、21-三体等)11例(1.1%);性染色体5例(0.5%),结构异常20例(2.1%),嵌合体9例(0.1%),正常染色体核型中发现染色体多态性改变56例(5.8%)。结论沈阳地区羊水染色体异常核型检出率较高,具有产前诊断指征的孕妇行胎儿羊水染色体诊断对防止先天缺陷有实用性价值。     

超声测量颈项透明层厚度对孕早期胎儿畸形的筛查效果观察

目的探讨超声测量颈项透明层厚度对孕早期胎儿畸形的筛查效果。方法通过对2017年7月-2018年12月在我院进行常规超声检查的孕早期孕妇为研究对象,测量颈项透明层厚度,对孕妇的妊娠结局、染色体核型和结构进行随访,分析颈项透明层不同界值在预测胎儿畸形特异度和敏感度差异。结果216例胎儿中,颈项透明层厚度<2.5 mm胎儿208例,染色体核体、结构正常胎儿203例,平均颈项透明层厚度为(1.60±0.39)mm。颈项透明层厚度≥2.5 mm胎儿8例,2例胎儿染色体异常,颈项透明层厚度平均值为(3.46±0.32)mm,两组差异具有显著性(P<0.05)。203例正常胎儿中,男性胎儿和女性胎儿所占比例及项透明层厚度无统计学意义(P>0.05);异常胎儿孕妇年龄较正常胎儿孕妇年龄明显增加(P<0.05);项透明层厚度临界值增加,敏感度逐渐下降,漏诊率随之提高。结论颈项透明层厚度为孕早期诊断胎儿染色体异常和结构异常的重要指标,对评价妊娠不良结局具有重要参考价值,值得推广应用。     

双胎妊娠孕早期双胎发育不均衡对新生儿结局的影响

目的探讨双胎妊娠孕早期两个胎儿间的发育不均衡对新生儿结局的影响。方法选择孕早期双胎孕妇120例,于孕11~12周行超声检查,将两个胎儿间头臂长(CRL)、颈项透明层厚度(NT)、胎儿心率(HR)、最大羊水深度(DVP)差异均<20%的孕妇纳入生理组(共74例孕妇148例胎儿),将上述四项指标中任一项≥20%的孕妇纳入病理组(共46例孕妇92例胎儿)。对两组孕妇分娩后新生儿结局情况进行随访,记录分娩时新生儿异常(脐带异常、输血综合征、畸形、心脏异常、死亡)例数,计算新生儿异常总发生率。所有患者随访至胎儿出生后3个月,记录出生时及出生后3个月新生儿体质量及两新生儿的体质量差异。结果生理组、病例组新生儿异常总发生率分别为1.35%(2/148)、8.69%(8/92),病理组新生儿异常总发生率高于生理组(P<0.05)。出生时两组新生儿体质量比较无统计学差异(P>0.05),但生理组两新生儿体质量差值小于病理组(P<0.05)。出生后3个月,生理组新生儿体质量大于病理组(P<0.05),两新生儿的体质量差值小于病理组(P<0.05)。结论双胎妊娠者孕早期双胎病理性发育不均衡可导致新生儿异常的发生率增高。     

孕中期血清学、超声检查在胎儿染色体异常筛查中的应用

目的观察孕中期血清学、超声检查在胎儿染色体异常筛查中的应用效果。方法采用化学发光法测定38 165例单胎孕妇血清中甲胎蛋白、游离人绒毛膜促性腺激素和(或)游离雌三醇浓度,利用随机配载软件计算胎儿21-三体、18-三体和神经管畸形风险值;采用系统超声检查孕中期的10 727例孕妇。血清学提示高风险胎儿者及系统超声检查提示胎儿结构异常者行羊膜腔穿刺羊水细胞培养核型分析。结果血清学检查异常核型检出率为4.0%(69/1 708)。超声检查对各种先天结构异常检出率为2.2%(236/10 727),异常核型检出率为28.8%(49/170)。超声检查胎儿异常核型检出率高于血清学检查(P<0.01)。血清学或超声检查之一异常并接受羊膜腔穿刺者1 819例,其中异常核型者103例,阳性率为5.7%。血清学、超声检查均异常者59例,其中异常核型检出率为25.4%(15/59),高于单一血清学检查(P<0.01),但与单一超声检查比较无统计学差异。结论孕中期血清学检查胎儿染色体异常假阳性率高,超声检查胎儿染色体检出率高于血清学检查。以血清学检查为基础,联合超声检查,可以提高产前胎儿染色体异常筛查准确率。     

经腹绒毛取样侵入性产前诊断60例报告

目的总结早孕期经腹绒毛取样(transabdominal chorionic villus sampling,TA-CVS)操作的适应证、并发症及胎儿结局。方法选取该院门诊孕妇60例,单胎妊娠,平均年龄(29.27±4.1)岁,平均孕周(12.61±0.86)周。手术适应证为胎儿染色体异常高危因素20例;双亲同型地贫携带者42例。无手术禁忌证,术前测量体温、血压、脉搏。超声引导TA-CVS,52例标本送染色体核型分析(染色体高危因素20例,因地贫基因诊断而同时送检32例),42例送检地中海贫血基因(β-地贫11例,α-地贫31例)。结果检出β-地贫双重杂合子或纯合子6例,重型α-地贫8例,血红蛋白H病6例。7例超声检测胎儿水肿/颈部囊性水囊瘤中检出常染色体三体3例。无手术并发症。1例术后2周流产,流产率为1.67%。结论 TA-CVS的优点在于早诊断、早干预,且胎儿丢失率低。主要产前诊断适应证是单基因遗传病和早孕期超声检测异常病例的染色体病检出。     

伴8号染色体异常急性单核细胞白血病临床特征与预后分析

目的探讨8号染色体异常急性单核细胞白血病(acute monocytic leukemia, AML-M5)的临床特征和预后。方法回顾性分析2016年1月至2018年1月浙江大学医学院附属第一医院143例初发AML-M5患者的临床资料及预后特征,并分析影响预后的因素。结果 143例初治AML-M5患者中,37例伴8号染色体核型异常[其中t(8;21)占6.99%(10/143),8号三体占16.08%(23/143),其他8号异常占2.80%(4/143)],73例核型正常,33例为其他非8号染色体异常。3组患者年龄、性别、血常规、骨髓细胞比例方面,无明显差异(P0.05),而伴8号染色体异常组倾向于低白细胞(P0.05)。131例接受化疗的患者,第一个疗程化疗缓解率为63.36%(83/131),1年生存率61.1%。单因素分析提示,年龄、第一次诱导化疗后缓解情况(是否缓解)、8号三体核型、治疗方式(是否联合造血干细胞移植)对预后有影响(P0.05)。多因素分析提示,影响预后的独立危险因素包括年龄≥60岁(HR=2.134,95%CI 1.204～3.784,P0.05)和确诊后第一次化疗缓解(HR=0.408,95%CI 0.227～0.733,P0.05)。结论 8号染色体为AML-M5患者易受累的染色体,累及该染色体的患者初诊白细胞比较低,预后不良。化疗缓解后行异基因造血干细胞移植有利于延长生存期。     

老年急性白血病患者的染色体核型分析

目的 探讨急性白血病患者的染色体核型分布特征及不同年龄组患者染色体预后分层特征.方法 采用骨髓短期培养和G显带技术对215例急性白血病患者进行染色体核型分析.结果 215例患者中,有足够可供分析分裂相者202例,检出异常克隆149例(73.8％),各年龄组异常克隆检出率分别为,≤30岁组73.0％(27/37),31～59岁组74.4％(64/86),≥60岁组73.4％(58/79),各年龄组异常克隆检出率差异无统计学意义(P=0.982).在检出分裂相的171例急性髓性白血病(AML)患者中,预后良好核型41例(24.0％),预后中等核型80例(46.8％),预后不良核型50例(29.2％);预后良好核型中以t(15;17)最多(占65.9％);预后中等核型中以正常核型为主(占53.8％);预后不良核型中以复杂异常为主(占84.0％).≤30岁组预后良好、中等及不良染色体核型所占百分比分别为50.0％、36.4％和13.6％;31～59岁组分别为24.3％、48.7％和27.0％;≥60组分别为16.0％、48.0％和36.0％.≤30岁组预后良好核型所占比例较其他两组高(分别为P=0.021和0.001),≥60岁组预后不良核型所占比例高于≤30岁组(P=0.046).29例急性淋巴细胞白血病(ALL)患者具有预后不良核型者10例.结论 急性白血病患者染色体核型分析可为预后分层提供重要依据,AML患者随着年龄增长预后不良核型比例逐渐增高.     

Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia

Cytogenetic studies (CG) of 475 chronic lymphocytic leukemia (CLL) cases showed trisomy 12 in 6.1% or 26% of patients with abnormal karyotypes. Fluorescence in situ hybridization (FISH) detected trisomy 12 in 35% of 117 CLL patients. Only 34.6% of cases detected by FISH were detected by CG. Twelve patients had low levels of trisomic cells (4% to 11%) relative to clonal B cells (47.5% to 86%), suggestive of clonal evolution. Untreated patients with trisomy 12 were predominantly male (P < .05) and had an increased incidence of splenomegaly (P < .03). Patients with trisomy 12 were more likely to be previously treated and had advanced Binet stage compared with those without trisomy 12. The median survival was shorter in patients with trisomy 12 (7.8 years) and patients with other chromosomal abnormalities without trisomy 12 by FISH (5.5 years) than in patients with diploid karyotypes (14.4 years). The response to fludarabine was similar to that of patients with diploid karyotypes, but there was a trend for earlier disease progression. FISH detected residual disease in all patients with trisomy 12 in complete (n = 6) or partial remission (n = 4). As few as 1 trisomic cell in 5,000 was detected by performing FISH on fluorescence-activated cell sorter-sorted cells. Trisomy 12 was absent in T cells in patients with trisomy 12. We conclude that FISH identifies trisomy 12 approximately 2.6 times more often than CG, readily identifies minimal residual disease, and predicts for a shorter median survival.     

Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients

We have analysed the clinical and laboratory features in 544 patients with chronic lymphocytic leukaemia (CLL) with available cytogenetics and fluorescence in-situ hybridization (FISH) analysis for trisomy 12 in half of them, to examine the correlation between chromosome abnormalities and clinical or laboratory parameters. Five chromosome groups were defined: (1) trisomy 12 (18%), detected as the sole abnormality or associated with other changes; (2) del(13)(q12–14) (7%); (3) other abnormal karyotypes (20%); (4) normal karyotype (41%); and (5) no divisions (14%). There were no differences in the age distribution between the five groups. Clinical stages (Binet) were: A (74%), B (12%) and C (14%). Stage A was common in cases with del(13q)(82%), normal (84%) and other abnormal karyotypes (74%), whereas it was less common in trisomy 12 cases (64%) and those with no divisions (48%). Typical CLL morphology was found in 83% of cases; 10% had more than 10% prolymphocytes (CLL/PL) and 7% had other atypical features. CLL with trisomy 12 was the only group with a high frequency of either CLL/PL (31%) or atypical morphology (24%). Atypical morphology and CLL/PL were even more frequent when trisomy 12 was associated with other chromosomal abnormalities (70% v 46%). The incidence of cases with CLL/PL and other atypical morphology was significantly lower in the other chromosome groups ( P <0.001. There were no differences in immunophenotype among the various groups except for a higher frequency of stronger Smlg and FMC7 expression in cases with trisomy 12, particularly those with CLL/PL and other atypical morphology. Our findings confirm that trisomy 12 defines a subgroup of CLL with more frequent atypical morphology, including CLL/PL, stronger SmIg and FMC7 expression, more advanced stages (B and C in 18%) and possibly worse prognosis.     

Spectrum and outcome of atrioventricular septal defect in fetal life

OBJECTIVES OF THE STUDY: to analyse the features and outcomes of different types of atrioventricular septal defects, detected during fetal life, as compared to postnatal data. MATERIAL AND METHODS: We analysed retrospectively the data concerning 82 fetuses with atrioventricular septal defect, diagnosed from 19 through 37 weeks gestation with a median of 26 weeks. In 46 cases (56.1%), the diagnosis has been made before the age of 24 weeks. RESULTS: Characteristics of the series--in 44 fetuses the atrioventricular septal defect was not associated with other cardiac anomalies, while 38 fetuses had a more complex form. Chromosomal anomalies were present in 33 of the fetuses (40.2%), more frequently in cases without associated intracardiac defects (56.8%). Trisomy 21 occurred in just over one quarter the series, and in 43.2% of cases without associated defects. In addition, 11% of fetuses had trisomy 18, and one had trisomy 13. Extracardiac anomalies were present in 12 of the fetuses (14.6%), more frequently in cases without associated abnormalities. Of fetuses with more complex defects, 46.4% had hypoplasia of the left ventricle and aorta. Complete atrioventricular block was present in 10 of the fetuses (12.2%), mainly in fetuses with other malformations, and particularly with left isomerism. Recurrence of congenital heart disease was observed in 5 of the fetuses (6.1%). OUTCOME: In 25 instances (30.5%) the parents opted for termination of pregnancy. Of 57 cases that continued through pregnancy, 9 fetuses died prior to term (15.8%), 32 died postnatally (56.13%) and only 16 fetuses (28.1%) survived. Overall, the mortality was higher in cases with associated malformations, in those with heart failure or those with atrioventricular block. Cardiac surgery was performed in 19 infants, with 5 dying postoperatively, and one late. CONCLUSIONS: Our data show a high prevalence of atrioventricular septal defect associated with other malformations when diagnosed during fetal life. This combination is less frequently associated with chromosomal and extracardiac anomalies, but more often with obstructive lesions of the left heart and with atrioventricular block. The association results in a less favourable outcome.     

Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait

Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.     

Prognostic significance of karyotypic abnormalities in B cell chronic lymphocytic leukemia: an update

Cytogenetic analyses by G-banding and/or Q-banding techniques of leukemic B cells were performed in 102 patients with chronic lymphocytic leukemia (CLL), including six with prolymphocytic leukemia (PLL), one with hairy cell leukemia (HCL), and one with Waldenstrom's macroglobulinemia (WM) from 1979 through 1983. Follow-up after cytogenetic study ranged from 24 to 70 months. Seventeen patients had stage 0, 10 had stage I, 31 had stage II, and 44 had stage III or IV. Adequate metaphases were obtained for karyotypic analysis in 86 (84%) of 102 patients. Of these 86 patients with adequate metaphases, 43 had normal karyotypes (50%) and 43 had abnormal karyotypes (50%), of which trisomy 12 was the most frequent. Ten patients had trisomy 12 as the sole abnormality, 14 had trisomy 12 in combination with other abnormalities, and the remaining 19 had other abnormalities without trisomy 12. Abnormal karyotypes were more frequently associated with patients with advanced stages than those with early stages of the disease. Response rate to chemotherapy was significantly higher in patients with normal karyotypes than in those with abnormal karyotypes. Of eight patients who subsequently developed Richter's syndrome, seven initially had complex karyotypic changes with or without trisomy 12. These observations suggest that the chances of development of Richter's syndrome in CLL patients with multiple chromosome changes may be much higher than in those with either simple trisomy 12 or a normal karyotype. Mean frequency of abnormal metaphases was significantly higher in patients with complex trisomy 12 in combination with other changes than in those with trisomy 12 as the sole abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tricuspid valve dysplasia or displacement in intrauterine life

In 450 cases of structural heart disease diagnosed prenatally, 38 fetuses (8.5%) had either a dysplastic or a displaced tricuspid valve. The tricuspid valve was dysplastic in 22 fetuses, all of which had evidence of tricuspid regurgitation resulting in right atrial dilation and increased cardiothoracic ratio. An associated abnormality of the pulmonary valve occurred in 16 fetuses. The remaining 16 fetuses had Ebstein's malformation, 14 with evidence of tricuspid incompetence at presentation and 10 with an associated abnormality of the pulmonary valve. Of the 38 cases, the pregnancy was interrupted in 17, spontaneous intrauterine fetal death occurred in 8, 11 infants died postnatally and 2 infants are still alive; additional abnormalities were found in 8 cases (chromosomal anomalies in 2, ventricular septal defects in 2, corrected transposition in 2, the Chiari malformation in 2, supraventricular tachycardia in 1 case and coarctation of the aorta in 1). Fetuses with severe abnormalities are selected for fetal echocardiography by the four chamber screening program and a high rate of natural loss both in intrauterine life and immediately after birth was observed in the 21 cases in which pregnancy was continued. This would explain the higher incidence of tricuspid valve disease in our prenatal compared with postnatal series. Although increased cardiothoracic ratio and associated lesions of the right ventricular outflow tract contribute to the poor outcome in the cases detected prenatally, the absence of these features does not always indicate a good prognosis because progression of disease can occur with advancing gestational age. No absolute measurement or single echocardiographic feature emerged as a consistent predictive factor of prognosis.     

Cytogenetic Studies in Preleukaemia Using the G-Banding Staining Technique

15 patients with preleukaemia were cytogenetically studied during the preleukaemic state by using the G-banding staining technique. It was found that 9 patients had a completely normal karyotype, while the other 6 showed various chromosomal abnormalities, numerical (trisomies in 5 cases) and structural (deletion in 1 case and a marker chromosome in 1 case). The abnormalities concerned group C in all 6 cases, while group A was involved in 3 cases. G-banding technique revealed that trisomy C affected the chromosomes nos 8 (2 cases) and 9 (3 cases); also a deleted chromosome 11 (11q-) was identified in 1 case and a marker chromosome in 1, the origin of which was established as a translocation between chromosomes 3 and 6. The abnormalities of group A concerned chromosome no 3. The abnormalities found in our cases, using the G-banding technique, were similar to those described in acute leukaemia.     

Karyotype in myelodysplastic syndromes: Relations to morphology,clinical evolution,and survival

One hundred eighty-eight unselected consecutive patients with “de novo” myelodysplastic syndrome (MDS) were studied cytogenetically. They were subclassified as 4 refractory anemia with ringed sideroblasts (RARS), 67 refractory anemia (RA), 58 refractory anemia with excess of blasts (RAEB), 40 RAEB in transformation (RAEB-t), and 19 chronic myelomonocytic leukemia (CMML). The overall incidence of chromosome abnormalities was 69%. The RAEB and RAEB-t patients showed karyotypic changes, more often than RA and CMML (76% and 100% vs. 56% and 42%, respectively). The most frequent single anomaly was del(5)(q13-q22q33) (22 cases), followed by monosomy 7 or del 7q (11 cases), del(11) (q14q23) (8 cases), trisomy 8 (4 cases). Complex karyotypes (defined by the presence of three or more structural or numerical abnormalities) were detected in 33 patients. With regard to the FAB classification, del (5)(q13q33) was associated with RA, and complex rearrangements with RAEB and RAEB-t. Leukemic transformation occurred in 66 patients (46%), none with a normal karyotype or del(11)(q14q23) as single abnormality. In patients carrying 5q- alone, acute evolution correlated with proximal breakpoint localization, being found in no case with del(5)(q13q33) but in three out of four cases with del(5)(q22q33). Acute leukemia (AL) progression happened in all cases with complex rearrangements and monosomy 7 or del(7q). Two of the four trisomy eight patients evolved in AL. By using the Cox proportional hazard regression analysis it was demonstrated that the karyotype abnormality was a significant predictor of leukemic transformation (P < 0.001). Patients with abnormal karyotypes without complex abnormalities had a survival (median survival 12 months) shorter than that of cases with only normal metaphases (median 83 months) (P < 0.001); patients with a mixture of normal/abnormal metaphases had a median survival of 31 months. The median survival for complex karyotypes was 7 months. Among cases with single defects, del(5)(q13q33) showed the best survival (64 months), mono- somy 7 and del (7q) the worst (7 months) (P < 0.001). © 1994 Wiley-Liss, Inc.     

Atrioventricular septal defects diagnosed in fetal life: associated cardiac and extra-cardiac abnormalities and outcome

OBJECTIVES: We sought to establish the outlook for fetuses diagnosed with atrioventricular septal defect (AVSD) prenatally and its relation to additional cardiac, extracardiac and chromosomal abnormalities. BACKGROUND: Prediction of likely outcome of AVSD presenting prenatally is complicated by the wide variation in associated features. METHODS: Computerized records from 14,726 pregnancies referred to a fetal cardiology center were reviewed retrospectively. Pathological reports, postnatal records, follow-up inquiries and review of echocardiographic video recordings supplemented analysis of the records for all those with AVSD. RESULTS: Atrioventricular septal defect was confirmed in 301 fetuses. Eighty-six (39%) of the 218 with known karyotype had trisomy 21, and 21/218 (10%) had other chromosome abnormalities. Right isomerism occurred in 37/301 (12%) fetuses, left isomerism in 62 (20%), mirror image atrial arrangement in 2 (1%), and 200 (67%) had usual arrangement. Atrioventricular septal defect occurred without any other intracardiac abnormality in 155 fetuses (51%). Extracardiac abnormalities and nonkaryotypic syndromes were evident in 40 fetuses (13%, confidence interval [CI] 9.5-17.1%). Uncomplicated cardiac anatomy was significantly associated with the presence of karyotype abnormality (p < 0.0001). Parents opted for termination of pregnancy in 175/298 (58.5%). For the continuing pregnancies, Kaplan-Meier estimates for live birth, survival past the neonatal period and survival to three years were 82% (CI 75.3-88.9%), 55% (CI 46.0%-0/64.3%) and 38% (CI 27.1-48.6%), respectively. Fetal hydrops and earlier year of diagnosis were independent variables with adverse influence on survival. CONCLUSIONS: Despite some improvements in the outlook for AVSD diagnosed prenatally, the overall prognosis remains considerably poorer than that implied from surgical series. The detection of associated cardiac and extracardiac abnormalities is important in order to give the best indication of the likely outcome when counseling parents.     

Aplastic anemia or aplastic preleukemic syndrome?

 The incidence of aplastic anemia appears to be relatively high in some parts of the world, including Pakistan. Since some of the etiological factors are shared by aplastic anemia and the preleukemic syndrome, there is a strong possibility that a proportion of cases of aplastic anemia may in fact be preleukemia.The study of chromosomes offers a relatively easy method of detecting cases of preleukemia, because some chromosomal abnormalities are frequently observed in this condition. Chromosomal studies were carried out in peripheral blood cell cultures of 31 patients with otherwise typical aplastic anemia. Chromosomal abnormalities were detected in 7 (22.5 %) cases. The most common chromosomal abnormality detected was trisomy 8, seen in four cases. Other abnormalities detected were 22q-, t(14;22) and t(15;21), in one case each. These abnormalities have been found to be associated with AML, MDS, ALL, and NHL as well. We hypothesize that a proportion of cases of otherwise typical aplastic anemia may in fact be due to a leukemic process in evolution. Received: 7 April 1997 / Accepted: 16 June 1997