598例妊娠中晚期胎儿超声异常与染色体异常的关系

目的:探讨妊娠中、晚期胎儿超声异常时染色体异常情况,以指导脐血穿刺的选择。方法:对我院胎儿超声异常的598例妊娠中、晚期孕妇取脐血进行染色体检查,分析胎儿超声结构异常及超声软指标异常的异常染色体检出率及异常染色体分类。结果:598例孕妇中,染色体异常61例,检出率10.20%,其中三体儿42例,占染色体异常的68.85%;超声结构异常胎儿染色体异常检出率明显高于超声软指标异常胎儿(P0.05);2项、3项及以上超声软指标异常染色体异常检出率明显高于单项软指标异常胎儿(P0.05);鼻骨缺失染色体异常检出率41.67%,单脐动脉染色体异常检出率12.24%;超声异常合并高龄孕妇组染色体异常检出率明显高于合并低孕龄组(P0.05);超声异常合并羊水过多组异常染色体检出率明显高于合并羊水正常组(P0.05)。结论:当有胎儿超声结构异常、超声软指标鼻骨缺失、两项及以上软指标异常、超声软指标异常合并高龄或羊水过多的情况时,染色体异常发生率明显增加,建议行脐血管穿刺染色体检查。     

妊娠中晚期超声软指标与胎儿染色体异常及其围生结局

目的:探讨妊娠中晚期超声软指标与胎儿染色体异常的关系及其对妊娠结局的影响。方法:回顾性分析2012年4月至2015年12月于四川省人民医院就诊的妊娠中晚期(孕18~32周)超声检查发现软指标异常但未合并明确结构异常1141例患者的临床资料,分析其产前诊断、胎儿染色体情况及围生结局。结果:1检测出24例胎儿染色体异常,其中10例为唐氏筛查(唐筛)低风险,5例为临界风险,3例为高风险;9例无创基因检测高风险。18例引产,6例正常分娩,新生儿正常。2单项超声软指标异常者胎儿染色体异常检出率为1.81%(20/1107),两项超声软指标异常及以上者胎儿染色体异常检出率为11.76%(4/34);两组比较差异有统计学意义(P0.05)。3不同部位的超声软指标异常胎儿染色体异常检出率:鼻骨缺失或发育不良为31.58%(6/19),颈后皮肤皱褶(NF)增厚为25.00%(1/4),脉络丛囊肿为5.38%(7/130),侧脑室增宽为4.27%(5/117)。结论:妊娠中晚期超声软指标两项及以上异常和鼻骨缺失、发育不良及NF增厚的异常胎儿有较高的染色体异常检出率,建议可行介入性产前诊断;单项超声软指标及其他部位异常的可结合唐筛和无创基因检测,以获得良好围生儿结局。     

超声软指标在产前染色体异常系统筛查中的临床价值分析

目的分析胎儿超声软指标与染色体异常的相关性,探究超声检查在胎儿染色体异常的筛查中的临床价值。方法选取河北省邯郸市中国人民解放军第285医院近5年来早中孕期(11~28周)检查提示胎儿超声软指标阳性的病例178例均接受胎儿染色体核型检查,对异常染色体核型的检出结果进行统计分析。结果 178例胎儿中染色体异常19例,其中不良结局的染色体核型共11例(非整倍体9例,结构异常2例),多个软指标阳性染色体异常的发生率为42.11%,显著高于单个软指标阳性的6.92%,差异有统计学意义(P0.01)。结论对于多个超声软指标阳性的孕妇,建议行介入进一步明确诊断,对于单个软指标阳性的病例,应结合孕妇年龄等其他因素进行评估,减少介入性检查。     

产前系统超声筛查与胎儿染色体异常的关系

目的:探讨产前系统超声筛查中晚孕期胎儿结构异常对指导进行侵入性产前诊断的价值.方法:2008年1月至2009年6月对我院中晚孕期孕妇行系统超声及超声心动图筛查,发现胎儿异常时经产前咨询及孕妇知情同意后,进行侵入性产前检查即羊水或脐静脉穿刺,进行染色体核型分析,分析各种类型的超声异常表现与染色体异常发病风险的关系.结果:...     

不同孕周段针对性超声检查的价值及局限性分析

目的:探讨不同孕周段针对性超声检查在产前筛查中的应用价值。方法:回顾分析2008年1月至2011年11月在我院行超声检查的孕妇的资料,其中,早期超声筛查2820例,超声系统筛查44 416例,常规超声检查152 528例。结果:早期超声筛查发现染色体异常高危病例52例,占检查人数的1.84%,最终确诊染色体异常7例,结构异常13例;中孕期系统超声筛查发现胎儿结构异常1279例,占2.88%,其中多发畸形258例;晚期常规超声检查发现胎儿异常545例,占0.36%。中晚期结构异常中检查出染色体异常15例。超声检查共漏诊21例,其中心脏畸形12例,其他畸形9例。结论:11～14周早期胎儿超声筛查,不仅能够有效检出染色体异常的高危胎儿,而且能早期排除胎儿早发和严重的结构异常。中孕期产前超声系统筛查是检查发现胎儿结构异常的重要方法和时段。晚孕期的超声检查对胎儿迟发性畸形的检查有重要的临床价值。     

胎儿淋巴水囊瘤与染色体异常的相关性研究及妊娠结局分析

目的:探讨胎儿颈部淋巴水囊瘤(CCH)与染色体异常的相关性,以及早孕期CCH胎儿的妊娠结局。方法:选取2012年1月1日至2016年6月1日在广州医科大学附属第三医院胎儿医学科门诊行早孕期NT筛查发现CCH的胎儿160例。孕妇均行产前诊断,对染色体及基因芯片结果未见异常的胎儿,建议孕妇于妊娠20～24周接受详细的胎儿III级排畸超声筛查。新生儿随访时间为出生后2～25个月。结果:160例行遗传学诊断的早孕期CCH样本中,染色体核型分析44例,行高分辨CMA分析116例。染色体异常82例,其中最常见的染色体异常为Turner's综合征(31例,33.7%),其次为18三体(24例,26.1%)、21三体(17例,18.5%),13三体7例,染色体平衡易位2例,染色体嵌合1例。基因芯片异常10例,其中6例致病性拷贝数异常。染色体及芯片未见异常的68例中,除10例死胎外,发现超声结构异常18例。染色体、芯片及超声均未见异常且选择继续妊娠的病例中,活产率为98%。截止随访日,活产胎儿暂未发现明显异常。胎儿心脏异常尤其是室间隔缺损在非染色体异常病例中的发生率较高。26例双胎中,约57.7%发现明显染色体异常,染色体检查、芯片及超声检查均未见异常的病例中,选择继续妊娠的4例双胎均活产健康。结论:对于早孕期CCH的预后,需排除常见的染色体异常及致病性拷贝数变异,同时还需结合胎儿排畸超声情况综合判断。如均未见明显异常,且后期未发生胎儿水肿的孤立性淋巴水囊瘤的胎儿出生后预后良好。     

早孕期胎儿鼻骨缺失与染色体异常关系的研究

目的:探讨早孕期胎儿鼻骨缺失与胎儿染色体异常之间的关系。方法:回顾性分析2016年1月至2017年12月广州医科大学附属第三医院产前诊断及胎儿医学中心和福建医科大学附属第一医院超声影像科早孕期超声检查提示胎儿鼻骨缺失的相关资料,分析胎儿单纯鼻骨缺失及其在合并其他超声异常时对诊断染色体异常的价值。结果:高龄孕妇的胎儿单纯鼻骨缺失及合并其他超声异常时胎儿染色体异常的发生率分别为6.78%和75.00%,同非高龄孕妇的胎儿染色体异常率(分别为0.80%和42.50%)比较,差异均有统计学意义(P<0.05)。胎儿单纯鼻骨缺失的染色体异常率为2.72%,当合并其他异常指标时,胎儿染色体异常率升至58.75%,差异有统计学意义(P<0.01)。胎儿鼻骨缺失在合并颈项透明层(NT)增厚时,胎儿染色体异常的总发生率为60.81%。当NT>3.5 mm时胎儿染色体异常率达77.78%,与NT≤3.5 mm时的染色体异常发生率(34.48%)比较,差异有统计学意义(P<0.05)。结论:早孕期超声检查提示胎儿鼻骨缺失时,需详细的胎儿超声结构筛查评估,当发现合并其他超声异常时,临床医师应向孕妇提供遗传咨询,建议行产前诊断以排除胎儿染色体异常。     

9例18三体综合征胎儿的产前诊断

目的探讨利用孕妇血清筛查和胎儿超声筛查进行18三体综合征胎儿产前诊断的有效性。方法对36例首诊主诉为产前筛查胎儿18三体高危、92例首诊主诉为胎儿超声有异常发现的孕18~32周孕妇共128例，进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128例胎儿核型中，9例为18三体综合征，2例为其它染色体异常，染色体异常发现率为8．59％（11／128）。首诊主诉为18三体高危发现18三体4例，异常发现率11．11％（4／36）；首诊主诉胎儿超声异常发现18三体5例，其它染色体异常2例，异常发现率7．61％，其中2例18三体合并有筛查高危和超声异常。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18三体胎儿的有效筛查手段。     

产前胎儿超声异常标记作为侵入性产前诊断指征的临床应用

目的:探讨产前胎儿超声异常标记作为侵入性产前诊断指征的临床应用。方法:选择由于产前超声检查见胎儿异常标记而行产前胎儿染色体核型分析的孕妇750例,检测胎儿的染色体异常率。对孕妇年龄<35岁(A组,n=658)与≥35岁(B组,n=92)、超声检查到胎儿有单项异常标记(C组,n=496)与胎儿有≥2项异常标记(D组,n=254),分别比较染色体异常率。结果:750例孕妇中检出胎儿染色体数目异常44例,胎儿染色体异常率为5.9%。A组检出染色体异常率为4.6%(30/658),显著低于B组的15.2%(14/92)(P<0.01)。C组检出染色体异常率为2.8%(14/496),显著低于D组的11.8%(30/254)(P<0.01)。结论:胎儿超声异常标记作为侵入性产前诊断指征,会有较多的胎儿染色体异常被检出,但须合理和谨慎选择。     

妊娠中期羊水染色体检查662例临床分析

目的 分析妊娠中期染色体病高危胎儿染色体病的发生状况.方法 对2003年9月至2007年3月间中国医科大学附属盛京医院662例染色体病高危孕妇进行羊膜腔穿刺,采取羊水细胞培养,制备中期染色体,分析胎儿核型,进行产前诊断.结果 发现染色体异常21例,异常率3.2%,其中数目异常11例,结构异常10例,不同产前诊断指征分组中的异常率不同,以夫妇双方之一为平衡易位携带者组异常率最高,为53.8%.结论 妊娠中期对染色体病高危孕妇进行羊水细胞培养染色体核型分析是产前诊断的重要手段,孕母血清筛查阳性、高龄、超声检查异常及染色体平衡易位携带者是羊水染色体检查的指征.     

Second trimester prenatal ultrasound for the detection of pregnancies at increased risk of Down syndrome

OBJECTIVE: To determine the association between second trimester ultrasound findings (genetic sonogram) and the risk of Down syndrome. METHODS: Prospective population-based cohort study of women who were at increased risk of chromosome abnormality based on serum screening. RESULTS: Overall 9244 women with singleton pregnancies were included, including 245 whose fetuses had Down syndrome. Overall, 15.3% of the women had an abnormal genetic sonogram, including 14.2% of pregnancies with normal fetuses and 53.1% of those with Down syndrome. If the genetic sonogram were normal, the risk that a woman had a fetus with Down syndrome was reduced (likelihood ratio 0.55 [95% CI 0.49, 0.62]) However, if the normal genetic sonogram were used to counsel these high-risk women that they could avoid amniocentesis, approximately half of the cases of Down syndrome (115 of 245) would have been missed. The isolated ultrasound soft markers were the most commonly observed abnormality. These were seen in a high proportion of Down syndrome fetuses (13.9%) and normal fetuses (9.3%). In the absence of a structural anomaly, the isolated ultrasound soft markers of choroid plexus cyst, echogenic bowel, renal pyelectasis, clenched hands, clinodactyly, two-vessel umbilical cord, short femur, and short humerus were not associated with Down syndrome. Nuchal fold thickening was a notable exception, as a thick nuchal fold raised the risk of Down syndrome even when it was seen without an associated structural anomaly. LIMITATIONS: All women included in this study were at high risk of Down syndrome based on serum screening, and thus the results of this study cannot be used as a basis to modify maternal age-related risk. CONCLUSIONS: The accuracy of the genetic sonogram is less than previously reported. The genetic sonogram should not be used as a sequential test following serum biochemistry, as this would substantially reduce the prenatal diagnosis of Down syndrome cases. In contrast to prior reports, most isolated soft markers were not associated with Down syndrome.     

Ultrasonographic soft markers of aneuploidy in second trimester fetuses

ObjectiveTo evaluate ultrasound “soft markers” used in fetal genetic screening.OptionsUltrasound screening at 16–20 weeks is one of the most common genetic screening tests used during pregnancy. The practical concern for ultrasound screening is false-positive and false-negative results. The use and understanding of ultrasound soft markers and their screening relative risks are an important option in the care of pregnant women.IntroductionChromosomal abnormalities occur in 0.1–0.2% of live births, and the most common clinically significant aneuploidy among live-born infants is Down’s syndrome (trisomy 21). Soft markers of aneuploidy are nonspecific, often transient, and can be readily detected during the second and third trimester ultrasound. The most commonly studied soft markers of aneuploidy include a thickened nuchal fold, mild fetal pyelectasis, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst. There is a great deal of interest in the ultrasound detection of aneuploidy, as evidenced by the large number of publications in the literature on this topic.     

Expected performance of second trimester maternal serum testing followed by a 'genetic sonogram' in screening of fetal Down syndrome

OBJECTIVE: To assess the efficacy of screening for fetal Down syndrome through the sequential provision of second trimester maternal serum tests and fetal ultrasound (the 'genetic sonogram'). METHODS: Monte Carlo modeling was used to generate typical results for second trimester serum screening. Serum test likelihood ratios were then multiplied by likelihood ratios associated with the provision of a genetic sonogram. The impact of adding the genetic sonogram on the detection rate (DR) and false-positive rate (FPR) were assessed for typical protocols that are currently in use. The effect of expanding the number of women who receive the genetic sonogram, variation in the marker frequencies in the genetic sonogram, and a multivariate Gaussian model that incorporated both serum and ultrasound measurements as continuous variables were also considered. RESULTS: When the genetic sonogram is offered only to those women who are screen-positive by serum testing, there can be a substantial reduction in the number of women with an indication for amniocentesis but also some loss in detection. The extent of these changes will partially depend on the serum tests and cutoff used. Providing the genetic sonogram to more women can reduce loss in detection without resulting in high amniocentesis rates. As a sequential screening tool, the genetic sonogram can be improved by incorporating markers that have a high frequency in affected pregnancies and by using ultrasound measurements as continuous variables. CONCLUSION: It should be possible to provide highly effective multistep screening protocols that maximize the benefits of both maternal serum and ultrasound while minimizing the amount of testing offered.     

An isolated intracardiac echogenic focus as a marker for aneuploidy

OBJECTIVE: This study was undertaken to evaluate the relationship of an isolated fetal intracardiac echogenic focus in a population of patients with a mixed risk for aneuploidy when presenting for prenatal diagnosis. STUDY DESIGN: All women referred to our institution for screening ultrasound were prospectively evaluated for the presence of an intracardiac echogenic focus in the fetal heart. Each patient was evaluated for the presence of clinical risk factors including ultrasound findings, biochemical screening, and maternal age. The population of patients was then described and neonatal outcomes were obtained. RESULTS: A total of 10,875 patients were referred and 176 cases of fetal intracardiac echogenic foci were evaluated. There was an overall prevalence of 1.6% in our population. The patients with other ultrasound findings and/or maternal age older than 35 years who underwent amniocentesis had 3 abnormal karyotypes identified and had identifiable risk factors. In the group less than 35 years, the relative risk was 2.55 of having an amniocentesis for an isolated echogenic focus (with no cases of fetal aneuploidy found) in comparison with our referred group of nonadvanced maternal age patients without any ultrasound markers or findings. CONCLUSION: This isolated echogenic finding appears to be a benign variant and not an increased risk for fetal aneuploidy. The chromosomal abnormalities were seen in the group with risk factors including maternal age and/or other ultrasound findings. Evaluation of maternal age, biochemical markers, and ultrasound markers should be used together to help determine the risk of patients with an isolated echogenic focus.     

Ultrasound soft markers of chromosomal abnormalities; an ethical dilemma for obstetricians

With high-resolution ultrasound, it is possible to examine fetal anatomy in great detail. Soft markers promise to be useful in screening for chromosomal abnormalities when considered alongside maternal age, but the premature introduction of soft markers into routine fetal screening might have caused physical or psychological harm to an unknown number of expectant parents and unborn children.     

The role of the second trimester genetic sonogram in screening for fetal Down syndrome

The Genetic Sonogram is an ultrasound examination done on second trimester fetuses that not only evaluates the fetus for structural malformations, but also searches for the sonographic markers of fetal Down syndrome. The main markers that comprise the genetic sonogram include the nuchal fold, short femur and humerus, pyelectasis, hyperechoic bowel, echogenic intracardiac focus, and any major abnormality. The absence of any marker on a second trimester scan conveys a 60-80% reduction in prior risk of Down syndrome based on advanced maternal age or serum screen risk. The presence of sonographic markers, either singly or in combination, will raise the baseline risk of Down syndrome using likelihood ratios calculated for each individual marker. Using this approach, approximately 75% of fetuses with Down syndrome can be identified by modifying the patient's baseline risk according to the results of the ultrasound. The second trimester scan will likely continue to play an important role in the future in the detection of aneuploidy.     

Isolated Intracardiac Echogenic Focus on Routine Ultrasound: Implications for Practice

Ultrasound is widely used as a screening tool for fetal anomalies. An intracardiac echogenic focus (ICEF) is associated with fetal aneuploidy, particularly trisomy 21, when found with other minor abnormalities known as soft markers. However, when found in isolation, intracardiac echogenic foci are morphologic variations with little or no pathologic significance for the fetus. Ambiguity about the significance of ICEF and other soft markers and the lack of preparation prior to ultrasound can result in unnecessary worry for women and their partners. A variety of tools exist that providers can use to help pregnant women and their partners make informed decisions about ultrasound and fetal screening.     

Correlation of ultrasound findings and biochemical markers in the second trimester of pregnancy in fetuses with trisomy 21

OBJECTIVE: The aim of the present study was to assess possible correlations between ultrasound findings and maternal serum biochemical ('triple test') markers among fetuses with trisomy 21 in the second trimester of pregnancy. METHODS: The study was a retrospective cohort study of 72 pregnancies affected by trisomy 21 who had a second trimester ultrasound and biochemical screen performed at a single center between 1990 and 1999. The biochemical screen consisted of alpha-fetoprotein (AFP), total beta human chorionic gonadotrophin (hCG) and estriol (uE(3)). Marker levels were expressed in multiples of the median (MoM). The ultrasound findings assessed were major structural anomalies, short humerus length, short femur length, increased nuchal fold thickness (NF), hyperechoic bowel, echogenic intracardiac focus (EIF), ventriculomegaly, choroid plexus cysts and renal pyelectasis. RESULTS: Second trimester maternal serum biochemical markers and ultrasound findings appeared to be largely independent of each other. However, some significant correlations were observed. Estriol was significantly lower when a fetal cystic hygroma was detected on ultrasound compared to those with no cystic hygroma (0.40 vs. 0.70 MoM, p<0.05). The median hCG level was significantly lower in those pregnancies with a normal second trimester fetal ultrasound compared to those with positive ultrasound findings (2.07 vs. 2.87 MoM, p<0.05). Median hCG levels were also significantly higher in those cases with NF> or =5 mm as compared to those with NF<5 mm (2.99 vs. 2.49 MoM, p<0.05). This difference persisted after exclusion of the five cases with cystic hygromas (2.99 vs. 2.49 MoM, p<0.05). A significant positive correlation was observed between log(10) hCG and log(10) NF MoM (Spearman's rho=0.252, p<0.05). NF was significantly greater among fetuses with an identifiable cardiac defect compared with those without a detectable cardiac defect (median of 7.0 mm vs. 3.8 mm, p<0.01). This difference persisted when expressed as multiples of the median (2.8 vs. 1.3 MoM, p<0.01). CONCLUSION: Second trimester ultrasound and biochemical markers are largely independent in fetuses with trisomy 21, however significant correlations between the two were observed in the present series. These may be important in screening protocols that combine second trimester ultrasound and biochemical markers.     

Down syndrome risk estimation after normal genetic sonography

OBJECTIVE: The objective of this study was to determine whether there are any indication-specific variations in risk reduction for fetal Down syndrome after a normal genetic sonogram. STUDY DESIGN: A second-trimester genetic sonogram was offered to all pregnant women who were at increased risk for fetal Down syndrome (>/=1:274) because of either advanced maternal age (>/=35 years), an abnormal triple screen, or both. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. Normal genetic sonography was defined as the absence of all ultrasound aneuploidy markers. RESULTS: The overall prevalence of fetal Down syndrome in the tested population was 1.41% (53/3,753 pregnancies); however, in the presence of normal genetic sonography, the overall prevalence of fetal Down syndrome was 0.21% (7/3,291 pregnancies). The overall risk reduction for fetal Down syndrome in the presence of normal genetic sonography was 6.64-fold (95% CI, 3.01-14.62); the overall negative likelihood ratio was 0.15 (95% CI, 0.07-0.33). In the presence of normal genetic sonography, the risk for fetal Down syndrome was reduced by 83% in patients with advanced maternal age, 88% in patients with abnormal triple screen, 89% in patients with abnormal triple screen who were <35 years old, and 84% in patients who had both abnormal triple screen and advanced maternal age. CONCLUSION: There were no significant variations in the risk reduction for fetal Down syndrome in the presence of normal genetic sonography. Regardless of the indication for testing, the likelihood for fetal Down syndrome was reduced by 83% to 89%. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis.     

Role of ultrasound for Down syndrome screening in advanced maternal age.

OBJECTIVE: To determine the sensitivity and false-positive rate of Down syndrome screening by use of maternal serum screen and the genetic sonogram in women > or =35 years of age. STUDY DESIGN: We searched our perinatal databases retrospectively from January 1992 to January 2000 for the following criteria: known Down syndrome fetus or newborn, advanced maternal age, and genetic sonogram from 14-24 weeks' gestation. The a priori maternal age or maternal serum screen risk was modified by likelihood ratios for ultrasound markers. Without markers the risk was reduced by 50%. The cut-off was 1:270. RESULTS: Age and maternal serum screen had a sensitivity of 90.5% and a false-positive rate of 27.1%. Age and ultrasound had a 95.2% sensitivity and 43.5% false-positive rate, whereas the combination of age, maternal serum screen, and ultrasound had a 97.6% sensitivity and a 22.0% false-positive rate. CONCLUSION: The combination of age, maternal serum screen, and ultrasound improves the sensitivity for Down syndrome detection in the advanced maternal age population.