Fetal hydrops and anemia as signs of Down syndrome

Before the 20th week of gestation, the most common cause of nonimmune hydrops fetalis is chromosomal abnormalities. Herein, we report a case of fetal hydrops, anemia, and intrauterine growth retardation that presented at 27 weeks of gestation with a negative chromosomal abnormality screening. Cordocentesis and karyotype analysis revealed fetal pancytopenia and Down syndrome. Down syndrome rarely presents with fetal hydrops and anemia. Therefore, when hydrops and anemia are diagnosed, especially in the second trimester of gestation, the possibility of Down syndrome should be kept in mind. In addition, if the pregnancy results in a live birth, the baby should be examined for transient abnormal myelopoiesis.     

孕中期联合血清学和NIPT进行唐氏综合征筛查的回顾性分析

目的:探讨联合孕中期血清学筛查(second trimester serum screening,STSS)和胎儿染色体非整倍体无创DNA产前检测(noninvasive prenatal testing,NIPT)进行唐氏综合征(Down syndrome,DS)筛查在天津地区的临床应用价值。方法:对10 429例15~20~(+6)周妊娠妇女进行二联STSS,设定1/270为DS高风险切割值,所有妊娠妇女均具有妊娠结局随访记录。对二联STSS结果为DS高风险的妊娠妇女建议羊膜腔穿刺,同时告知NIPT的范围及局限性,由妊娠妇女自愿选择;建议二联STSS风险值在1/1 000~1/270之间(含1/1 000)的低风险妊娠妇女,及风险值小于1/1 000的高龄(预产期年龄≥35岁)妊娠妇女行NIPT。联合筛查结果以NIPT结果为最终筛查结果,若妊娠妇女没有进行NIPT,以二联STSS结果为最终筛查结果。结果:二联STSS的DS检出率为73.33%(11/15),假阳性率5.75%(600/10 429),阳性预测值为1.80%(11/611);NIPT的DS检出率为100%(13/13),阳性预测值为100%(13/13);孕中期联合筛查的DS检出率为93.33%(14/15),假阳性率为1.62%(169/10 429),阳性预测值为7.65%(14/183),较单纯二联STSS方案DS阳性预测值有所提高(P=0.000)。结论:联合STSS和NIPT的DS筛查能够提高二联STSS的阳性预测值,减少因侵入性产前诊断造成的胎儿流产,为天津地区提供可参考的DS产前筛查方案。     

血清学筛查与胎儿超声检查在18、13三体综合征产前诊断中的应用

目的:探讨利用孕妇血清学筛查和胎儿超声检查进行18、13三体综合征胎儿产前诊断的有效性。方法:①对78例(A组)产前血清学筛查18、13三体高风险孕妇,拒绝进行产前诊断的孕妇进行随访观察。②对56例(B组)首诊主诉胎儿超声检查有结构异常的孕妇、134例(C组)首诊主诉为产前血清学筛查胎儿18三体高风险的孕妇,于孕18～32周行羊膜腔穿刺羊水细胞培养,或脐血管穿刺脐血细胞培养染色体分析。结果:A组的18三体筛查高风险孕妇有2例出现B超检查结构异常而放弃妊娠,1例产后检查新生儿先天性心脏病。B组发现18三体3例,13三体3例,其他染色体异常7例,异常发现率23.21%(13/56);其中2例18三体合并有血清学筛查高风险。C组发现胎儿异常4例,其中2例确诊为18三体,异常发现率2.99%(4/134)。结论:孕妇血清生化指标筛查结合胎儿超声检查是产前检出18、13三体综合征胎儿的有效检查方法。     

游离胎儿DNA高通量基因测序技术在产前筛查的临床应用

目的:探讨应用孕妇血浆中游离胎儿DNA高通量基因测序技术在无创性产前诊断中的可行性.方法:采用化学发光法对22977例孕中期妇女进行唐氏综合征筛查,对筛查结果为高风险的1173例孕妇采用高通量基因测序技术检测母体血浆胎儿游离DNA,分析胎儿染色体拷贝数,检测结果为高危的孕妇再做羊膜腔穿刺及脐血穿刺术进行胎儿染色体核型分析.结果:1173例孕妇中游离胎儿DNA高通量基因测序技术检测出11例染色体高风险胎儿,羊水/脐血核型分析证实其中10例为染色体异常,分别为7例21-三体和2例18-三体,1例13-三体.游离胎儿DNA高通量基因测序技术的敏感度为100.00％(10/10),特异度为99.91％(1162/1163),假阴性率为0(0/1173),假阳性率为0.09％(1/1173).结论:母体血浆游离DNA高通量基因测序技术可用于胎儿染色体拷贝数异常的检测,有准确性高、假阴性和假阳性率低、无创取样的优点,但由于费用较高,可结合血清学唐氏综合征筛查在有条件的地区进行推广应用.     

唐氏综合征智力低下的细胞分子机制

唐氏综合征发生机制是母体21号染色体上某些基因过度表达引起各种基因表达失衡。解释发病机制2种假说：基因剂量效应假说和放大的发育不稳定假说。前一假说主要解释21号染色体上的剂量敏感的基因过度表达产生的效应,从而引起各种基因表达失衡的累积效应。发育不稳定假说认为．21号染色体上基因剂量整体失衡干扰了基因表达和基因调控,破坏细胞内环境平衡。Rachidi提出唐氏综合征智力低下的细胞分子机制模型：所有这些基因表达的失常共同导致脑部的一级表型．由此决定更为复杂的二级表型,直接导致唐氏综合征患者智力低下。     

产前行妊娠相关血浆蛋白A筛查联合FISH诊断Down综合征

目的 :应用单项妊娠相关血浆蛋白A(PAPP A)筛查与羊水间期荧光原位杂交 (FISH)产前诊断相结合预防妊娠Down综合征胎儿。方法 :采用酶联免疫方法 (ELISA)对孕周分别为 6～ 2 7周的 1839例孕妇进行母血PAPP A单项筛查 ,以低于同一孕周的中位数时视为可能妊娠Down综合征胎儿的高风险孕妇。取高风险孕妇羊水细胞直接进行间期FISH产前诊断并同时用部分羊水细胞遗传学检查作对照。结果 :检出 1例孕 7周孕妇其PAPP A值为 0 0 5 1U/L ,低于同一孕周中位数 2 0多倍。羊水细胞间期FISH结果显示 ,含 5个杂交信号的核占所有杂交核的 38 5 % ,与细胞遗传学分析的 2 1三体核型完全一致。结论 :单项PAPP A筛查与羊水间期细胞FISH相结合是早期防治妊娠Down综合征有效可行的方法。     

产前超声估测胎重多参数新回归方程及准确性比较

目的:创建新的适合于中国人的多参数回归公式用于胎重估测。方法:750例孕妇,在分娩前3d以内超声检查,记录胎儿双顶径(BPD)、头围(HC)、腹围(HC)和股骨长(FL),出生后记录新生儿体重。其中600例用于公式创建,采用非线性回归设计公式,另150例用于公式的验证。结果:Log10EFW=1.0163+0.0023(HC)+0.0603(AC)+0.2571(FL)+0.0011(BPD)(AC)-0.0074(AC)(FL)(R=0.846)。在验证组,新公式与其他常用公式相比,平均绝对误差及平均绝对百分误差均为最低,准确性较高。结论:新公式更适宜于评估中国胎儿体重。     

First trimester Down syndrome screening: public health implications

Down syndrome (DS) screening has been an integral part of routine prenatal screening for the last three decades. Recent efforts have been directed at developing additional non-invasive prenatal screening techniques that could not only improve sensitivity of prenatal screening, but also be employed in the first trimester to offer earlier diagnostic and interventional opportunities. Nuchal translucency has proven to be an effective and cost-effective screening test that, when combined with serum markers (hCG and pregnancy-associated plasma protein [PAPP-A]) in the first and/or second trimester, broadens the diagnostic possibilities and improves the diagnostic capabilities of current prenatal DS screening methods. Despite the potential benefits, significant operational issues regarding access to and availability of such testing may limit its widespread application and necessitates the maintenance of both non-sonographic and second trimester screening methods. The implementation of first trimester DS testing requires the development and maintenance of nationally standardized quality control systems to ensure the reliability of serum and ultrasound measurements and the accurate assessment of risk. Future efforts to improve prenatal screening should continue to emphasize the need for improved access to all aspects of prenatal care, stress the importance of provider education and the necessity for extensive patient counseling, and reinforce the role of patient education and choice.     

Value of humerus length shortening for prenatal detection of Down syndrome in a Thai population

OBJECTIVE: To assess the value of humerus length shortening for prenatal detection of Down syndrome in a Thai population. METHODS: A prospective study was performed on 3053 women undergoing second-trimester amniocentesis, between 16 and 24 weeks gestation, for the indications of advanced maternal age and a past history of chromosomal abnormality. Biparietal diameter (BPD) and humerus length measurements were obtained before the procedures. Regression equations relating BPD to humerus length were used to calculate observed humerus length/expected humerus length ratio in chromosomally normal and Down syndrome fetuses. Sensitivity, specificity, false-positive rate and likelihood ratio of a positive test result at various observed humerus length/expected humerus length ratios for detection of Down syndrome were calculated. A receiver-operator characteristic curve was used to determine the threshold screening ratio. RESULTS: There were 3003 chromosomally normal pregnancies and 24 fetuses with Down syndrome. The relationship between humerus length and BPD was: expected humerus length = 0.7403BPD - 5.1057, R2= 0.77, P < 0.001. Humerus length in Down syndrome fetuses was significantly shorter than in normal fetuses (P < 0.001). A ratio of 0.91 for observed humerus length/expected humerus length yielded a sensitivity of 41.7%, specificity of 88.3%, a false-positive rate of 11.7% and likelihood ratio of a positive test result of 3.63 (95% confidence interval 2.24-5.88) for detection of Down syndrome. CONCLUSIONS: Humerus length shortening in the second trimester appears to be a useful adjunctive screening parameter for fetal Down syndrome in a Thai population.     

2000例孕中期唐氏综合征的筛查分析

目的 :探讨孕中期筛查唐氏综合征 (Downsyndrome,DS)的临床意义。方法 :对 2 0 0 0例孕中期孕妇血清进行AFP和β hCG两项指标的筛查。 结果 :2 0 0 0例中 ,DS高风险 1 40例 ,筛查阳性率 7%。DS高风险 1 40例中 40例做了产前诊断 ,发现 1例常染色体 3号、4号相互易位 ,1例 9号染色体臂间倒位 ,1例Y染色体长臂缺失。 1 6例神经管缺陷(hervoustubedefect,NTD)高风险 ,占筛查总数的 0 .8% ,其中 5例晚期流产。结论 :对孕期母血清筛查是预防DS患儿出生的重要途径。对DS高风险孕妇及时产前诊断是阻断染色体病遗传的有效方法     

PREGNANCY: Triple-Test Screening in In Vitro Fertilization Pregnancies

Purpose: To determine whether the results of triple-test analysis differ between spontaneous and IVF pregnancies.Methods: The study population consisted of 140 women with singleton pregnancies, 70 by IVF, and 70 by spontaneous conception. The groups were matched for maternal age, gestational week, and laboratory batch. The levels of all triple-test markers—alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (u-E₃)—were compared between the groups.Results: Significantly higher HCG levels were detected in the patients with IVF pregnancies than in the control group (1.31 ± 0.8 vs. 0.95 ± 0.5 multiple of the medians, respectively, (p < 0.006), but there were no significant differences in AFP or u-E₃ levels. Overall, 18.5% of the IVF group were found to be screen-positive as compared with 11.4% of the control group (difference not statistically significant). Only 8 IVF pregnancies (11.4%) reached the lowest calculated risk possible (1:9999) compared with 17 (24.2%) in the control group (p < 0.05).Conclusions: Our findings support previous data demonstrating elevated maternal serum HCG in IVF patients in comparison with spontaneous ones.     

15230例孕中期唐氏筛查产前诊断的临床应用

目的:探讨孕中期唐氏筛查对检出胎儿染色体异常的预测价值。方法:2008年1月至2009年10月,采用时间荧光免疫分辨法对我院15230例孕中期(15～20+6周)妇女进行血清标志物甲胎蛋白(AFP)、游离雌三醇(uE3)、绒毛膜促性腺激素(β-HCG)3项指标进行检测,对于筛查结果为高风险的孕妇于孕20～24周行羊膜腔穿刺进行胎儿羊水细胞染色体核型分析,并对唐氏筛查情况进行效果评价。结果:984例孕妇唐氏筛查为高风险,高风险率为6.46%,其中唐氏综合征阳性孕妇736例,18-三体阳性78例,神经管缺陷阳性169例。有773例高风险孕妇接受羊水穿刺,发现胎儿染色体异常29例,异常检出率为3.75%,其中唐氏综合征11例,18-三体1例,69,XXX1例。唐氏筛查的敏感性和特异性分别为92.86%和95.25%。结论:孕中期唐氏筛查是预测异常胎儿和不良妊娠结局的有效手段之一,羊水细胞核型分析在产前诊断中具有重要的实用价值。     

Non-invasive prenatal screening of fetal Down syndrome by maternal plasma DNA sequencing in twin pregnancies

Non-invasive prenatal screening for fetal Down syndrome (NIFTY) by maternal plasma sequencing was performed in 12 subjects with twin pregnancies, including 11 with normal fetuses and 1 with discordant fetal Trisomy 21. For every sample, it was processed, sequenced and reported as soon as it was collected as other clinical samples for singleton pregnancies. The NIFTY test was negative in the 11 pregnancies carried normal fetuses, and was positive (high risk) in the case with discordant fetal Trisomy 21. The sensitivity and specificity were both 100%. This small case series suggested the NIFTY as a screening test for fetal Trisomy 21 is feasible in twin pregnancies.     

Prenatal diagnosis of Down syndrome: A 13-year retrospective study

Objective

The aim of this study is to summarize the experience on prenatal diagnosis of Down syndrome.

Fetal nuchal translucency in severe congenital heart defects: experiences in Northern Finland

Objective: To evaluate the performance of first-trimester measurement of fetal nuchal translucency (NT) in the detection of severe congenital heart defects (CHDs).

Methods: During the study period of 1 January 2008 – 31 December 2011, NT was measured in 31,144 women as a part of voluntary first-trimester screening program for Down’s syndrome in Northern Finland. NT was measured by personnel trained on the job by the experienced staff. No certification or annual audits are required in Finland. However, the recommendation is that the examiner should perform 200 scans on average per year. Severe CHD was classified as a defect requiring surgery in the first year of life or a defect that led to the termination of the pregnancy. All severe CHDs diagnosed during the study period in Northern Finland could not be included in this study since all women did not participate in the first-trimester screening and some cases were missing important data.

Results: Fourteen (17.7%) out of 79 severe CHDs were found with NT cutoff of 3.5?mm. Amongst the 79 severe CHD cases, there were 17 chromosomal abnormalities. With NT cutoffs of 2.0 and 1.5?mm the detection rates would have increased to 25.3% (n?=?20) and 46.8% (n?=?37). Using a randomly selected control group of 762 women with normal pregnancy outcomes, false positive rates (FPRs) were calculated. For NT cutoffs of 1.5, 2.0 and 3.5?mm, the FPRs were, 18.5, 3.3 and 0.4%, respectively.

Conclusions: A greater than 3.5?mm NT measurement in the first-trimester ultrasound is an indication to suspect a fetal heart defect but its sensitivity to detect severe CHD is poor. In our study, only 17.7% of severe CHDs would have been detected with an NT cutoff of 3.5?mm.