Fetal nuchal translucency thickness and risk for chromosomal defects

In normal pregnancy fetal nuchal translucency (NT) thickness increases with gestation, in trisomy 21 and other major chromosomal defects fetal NT is increased. The risk for trisomies can be derived by multiplying the a priori maternal age and gestation related risk by a likelihood ratio, which depends on the degree of deviation in fetal NT measurement from the normal median for that crown-rump length. In a pregnant population with a mean maternal age of 28 years, using the risk cut-off of 1 in 300 to define the screen positive group would detect about 80% of trisomy 21 fetuses for a false positive rate of 5%. It was estimated that, for a 5.4% false positive rate, 90% of trisomy 21 fetuses could be detected. Prospective studies have demonstrated that such results are achievable by screening with fetal NT and maternal serum free b-hCG and PAPP-A in the first-trimester. It is therefore essential that, in screening, attention is paid to the provision of high quality sonographic and biochemical services for early diagnosis of chromosomal defects.     

Fetal cardiac defects and increased nuchal translucency thickness: a prospective study

OBJECTIVE: The purpose of this study was to examine prospectively the association between increased nuchal translucency thickness and major cardiac defects in chromosomally normal fetuses. STUDY DESIGN: A prospective cohort study of 263 chromosomally normal fetuses with an increased nuchal translucency thickness at 11 to 14 weeks of gestation at a tertiary referral center was performed. The incidence of major cardiac defects was examined in relation to the fetal nuchal translucency thickness at the 11 to 14 week ultrasound examination. RESULTS: The nuchal translucency thickness measurements ranged from 2.2 to 8.0 mm (median, 3.1 mm). There were 13 cases of major cardiac defects in this cohort, which gave a prevalence of 49.4 of every 1000 fetuses. With the use of the 99th percentile of nuchal translucency thickness, the prevalence rose to 106.7 of every 1000 fetuses. CONCLUSION: In this population of chromosomally normal fetuses with an increased nuchal translucency thickness, the incidence of cardiac defects was high, which suggests that fetal echocardiography is indicated in this group.     

First trimester increased nuchal translucency associated with fetal achondroplasia

A 30-year-old woman, gravida 2, para 1, was referred for nuchal translucency, free beta-human chorionic gonadotropin (beta-hCG), and pregnancy-associated plasma protein A (PAPP-A) screening at 12 weeks gestation. The nuchal translucency was increased to 3.8 mm, resulting in a post-test result of 1:15 risk for Down syndrome by a combination of maternal age plus nuchal translucency, and 1:5 by a combination of maternal age plus nuchal translucency plus free beta-hCG plus PAPP-A. The patient underwent uncomplicated chorionic villus sampling that demonstrated a normal 46,XY fetus. The patient was then followed-up weekly by ultrasound. At 18 weeks gestation, generalized features of rhizomelic micromelia together with macrocrania and narrow thorax were seen. All fetal long bones were less than 2 standard deviations from the mean value. At that time, DNA analysis was performed on stored villi and a G380R mutation in the locus gene encoding for the fibroblast growth factor receptor 3 on chromosome 4p16.3 was found, leading to a prenatal diagnosis of achondroplasia. The couple opted for termination of pregnancy after counseling. Postmortem X-ray was done and confirmed the ultrasound diagnosis of achondroplasia. This is the second known case of increased nuchal translucency in the first trimester associated with prenatal confirmed diagnosis of fetal osteochondrodysplasia.     

Association between fetal nuchal translucency thickness in first trimester and subsequent gestational hypertension and preeclampsia

Increased fetal nuchal translucency (NT) in the first trimester is associated with adverse pregnancy outcomes. Whether the increased NT is also associated with an increased frequency of pregnancy-associated hypertension (PAH) is not known. Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome screening and delivered their babies at our hospital by September 2000 were enrolled into this study. Among these women, there are 46 cases of preeclampsia, 68 cases of gestational hypertension (GH); 665 women without any adverse pregnancy outcomes served as controls. Correlation analysis demonstrated that NT MoM (multiples of median) level had a positive association with maternal diastolic blood pressure at the time of admission for delivery (r = 0.104; p < 0.01). The severity of PAH was concordant with the stepwise increase of mean NT MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13 in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM) percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and 1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58 respectively. It is concluded that the pathological changes in the placenta responsible for the development of PAH may also influence the physiological decrease of NT thickness in late first trimester. However, the sensitivity of fetal NT measurement in first trimester is not sufficient as a single marker for predicting the pregnant women at risk for subsequent PAH.     

Submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency and normal karyotype

Objective: To investigate the submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency (NT) and normal karyotype.

Methods: Total of 296 fetuses with increased NT (≥3.0?mm) were tested by conventional karyotyping. When cytogenetic analysis showed normal chromosome, the pregnancies were then consulted for array-comparative genomic hybridization (CGH) analysis and received subsequent morphology scan between 20 and 24 weeks gestation. Submicroscopic chromosomal abnormalities were assessed and compared between the fetuses with and without structural defects.

Results: Chromosomal abnormality was identified in 19.9% (59/296) fetuses. Two hundred and twenty samples were tested by array CGH. Submicroscopic chromosomal abnormalities were detected in 9.1% (20/220) fetuses. For the fetuses with abnormal morphology scan, the detection rate of submicroscopic chromosomal abnormalities was higher than those with normal morphology scan (26.9% versus 6.7%, p?Conclusions: Submicroscopic chromosomal abnormalities should be accessed when the fetus was found to be with increased NT and normal karyotype, especially when the structural defects were found at second or third trimester.     

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities

Objective.?The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

Methods.?We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency.

Results.?We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%).

Conclusions.?The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.     

Serum parameters and nuchal translucency in first trimester screening for fetal chromosomal abnormalities

Objective To assess the relation between serum parameters and nuchal translucency in pregnancies affected by fetal aneuploidy in the first trimester.
Design Retrospective study of different serum parameters collected prior to chorionic villus sampling and measurement of nuchal translucency in relation to fetal aneuploidy.
Setting Switzerland (German and Italian sector) and Bregenz, Austria.
Population One thousand one hundred and fifty-one women aged 25 to 44 years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13.
Main outcome measure Fetal karyotype, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of nuchal translucency.
Results Serum PAPP-A was decreased in all common chromosomal abnormalities. Free β-hCG levels were increased in trisomy 21 but decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and other chromosomal abnormalities. Nine of twenty-three abnormal embryos had evidence of an increased nuchal translucency. Nuchal translucency, however, did not seem to be associated with any alteration in the levels of the biochemical parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A or an increased nuchal translucency was seen in two-thirds of all pregnancies with chromosomal abnormalities.
Conclusion A nuchal translucency 3 mm and depressed serum PAPP-A levels have a good predictive value in the detection of fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free 0-hCG and alpha-fetoprotein levels may give additional information. An increased nuchal translucency was not-associated with altered serum parameters. This would allow these different markers to be used in combination.     

First-trimester fetal heart block and increased nuchal translucency: an indication for early fetal echocardiography

Prevalence of congenital heart disease increases with nuchal translucency (NT) thickness. First-trimester fetal bradycardia may result from heart block associated with complex congenital heart disease. We report two cases detected in the first trimester of pregnancy, in which both fetuses showed an increased nuchal translucency and bradycardia. Fetal karyotype was normal in both fetuses. First-trimester fetal echocardiography was performed and, in both cases, complex congenital heart disease was diagnosed. We discuss the added role of fetal heart rate in first-trimester ultrasound screening, in fetuses with increased nuchal translucency and normal karyotype. We stress, as well, the importance of echocardiography performed in the first trimester as a potential tool for early diagnosis in selected cases.     

First trimester diagnosis of 13q-syndrome associated with increased fetal nuchal translucency thickness. Clinical findings and systematic review

13q-syndrome is a rare chromosomal disorder caused by partial deletion of the long arm of chromosome 13 with variable phenotypic presentation. Further sonographic features involve fetal growth restriction, bradycardia, encephalocele, facial dysmorphism and upper extremity deformity. We report a case of 13q-syndrome presenting as increased nuchal translucency diagnosed by chromosome studies and confirmed by array comparative genomic hybridization (CGH) analysis in the first trimester of pregnancy. Pregnancy was terminated at 14 weeks' gestation. The parents did not give consent for a postmortem examination. Furthermore we performed a systematic review of the international literature on previous cases of 13q-syndrome diagnosed prenatally. Our case emphasizes the importance of a detailed 11-14 week ultrasound assessment in diagnosing fetal chromosomal aberrations in combination with the modern aspects of array CGH, thus providing more precise and rapid prenatal diagnosis.     

Screening for fetal chromosomal abnormalities with nuchal translucency measurement in the first trimester

OBJECTIVE: To describe the detection rate of first-trimester chromosomal abnormality screening with nuchal translucency (NT) measurement and maternal age in our population. METHODS: We have screened the fetuses between 11 to 14 weeks' gestation according to the Fetal Medicine Foundation's (London) instructions and used the FMF's software to assess the risk based on maternal age, crown-rump length (CRL) and NT. Fetal karyotyping was offered when screening for Down syndrome identified a risk greater than 1 in 300. Sensitivity and false-positive rates were calculated for different cut-offs. RESULTS: Pregnancy outcome was obtained from 4,598 babies of 4,365 mothers. The median maternal age of the 4,365 women was 28.2+/-5.3 (range 15-47) years, and the median fetal CRL was 65.4+/-9.4 (range 45-81) mm. There was risk estimate of >or=1 in 300 in 214 fetuses (4.7%). Chromosomal abnormalities were identified in 32 fetuses, including 19 cases of trisomy 21, and 13 cases of other abnormalities. The sensitivity using NT and maternal age in detecting trisomy 21 with a cut-off 1 in 300 was 73.6% (14/19) with a false-positive rate of 4.7%. At a false-positive rate of 3%, with a cut-off level 1 in 210, the detection rate was 73.6%. The detection rate for all chromosomal abnormalities with a cut-off level 1 in 300 was 68.8% (22/32) at a false-positive rate of 4.7%. CONCLUSION: The first-trimester screening for chromosomal anomalies with NT measurement, when carried out according to the accepted standards of quality, is useful.     

胎儿颈项透明层增厚和静脉导管血流频谱异常与胎儿染色体异常的关系

目的探讨胎儿颈项透明层(nuchal translucency, NT)超声检查在早孕期胎儿筛查中的应用价值。 方法收集104例于广州市妇女儿童医疗中心诊断NT增厚的孕妇的染色体核型分析资料,回顾性分析胎儿NT增厚、静脉导管血流频谱异常与胎儿染色体异常的关系。 结果(1)9980例孕妇中,NT异常增厚的胎儿共104例,占1.0%,颈项透明层厚度为(3.7±1.2)mm;(2)104例NT异常增厚的胎儿中,有28例胎儿染色体核型异常,包括染色体数目异常22例,结构异常6例,其中前3位为21-三体综合征、18-三体综合征和47,XXX;(3)随着NT厚度的增加,染色体异常的检出率相应增加;(4)NT增厚及静脉导管血流频谱正常预测染色体异常的阳性预测值是20.93%,NT增厚及静脉导管血流频谱异常的阳性预测值是55.56%,其差异具有统计学意义( χ²＝7.07,P<0.01)。 结论在早孕期进行胎儿NT超声检查,NT增厚及静脉导管血流频谱异常联合筛查更能有效筛查出染色体核型异常的高危胎儿。     

Temporal relationship between increased nuchal translucency and enlarged jugular lymphatic sac

OBJECTIVE: To study the relationship between the volume of the jugular lymphatic sacs and nuchal translucency thickness in fetuses with increased nuchal translucency with advancing gestation. METHODS: Seventy-four fetuses with a nuchal translucency greater than the 95th percentile were examined weekly between 11 and 17 weeks of gestational age. The fetal neck region was studied by ultrasonography, followed by measurement of nuchal translucency and jugular lymphatic sacs. The measurements were analyzed using multilevel analysis. In case of termination of pregnancy postmortem examination was performed. RESULTS: In 40 euploid fetuses and 34 aneuploid fetuses, 159 measurements of jugular lymphatic sac volume and nuchal translucency thickness were analyzed. The volume of the jugular lymphatic sacs and gestational age showed a quadratic relation, which differed between euploid and aneuploid fetuses (P < .01). The maximum volumes were larger and present longer in fetuses with aneuploidy than in euploid fetuses (P < .01). In case of a cardiac anomaly, jugular lymphatic sac volume was larger than in cardiac normal fetuses (nonsignificant). Furthermore, the development of jugular lymphatic sac volume and increased nuchal translucency were related, whereby an increase of the nuchal translucency preceded enlargement of the jugular lymphatic sacs (P < .001). In each fetus an increase in jugular lymphatic sac volume was followed by a decrease with advancing gestation. The gestational age at maximum jugular lymphatic sac volume differed between fetuses, indicating a fetus-specific pattern. Nuchal translucency development showed a similar pattern. Postmortem examination confirmed distension of the jugular lymphatic sacs in all cases. CONCLUSION: Increased nuchal translucency is associated with abnormal lymphatic development, in which nuchal translucency enlargement precedes enlargement of jugular lymphatic sacs on ultrasound examination. Aneuploid fetuses have a more disturbed lymph angiogenesis. LEVEL OF EVIDENCE: III.     

First-trimester ductus venosus velocimetry in relation to nuchal translucency thickness and fetal karyotype.

AIM: To evaluate first-trimester ductus venosus flow in relation to nuchal translucency (NT) and fetal karyotype. METHODS: Ductus venosus flow was measured in fetuses with NT greater than or equal to the 95th centile (group A) and in fetuses with NT less than the 95th centile (group B). The waveforms were classified as normal if the lowest forward velocity during atrial contraction (ACV) was positive and abnormal if it was absent or negative. The results were compared with the fetal karyotype. RESULTS: Ductus venosus measurement was carried out in 330 fetuses. In group A, there were 156 fetuses: in 4 cases, it was not possible to obtain the measurement, and in the other 152 cases, 93 (61%) had a normal ACV and 59 (39%) an abnormal ACV. NT thickness was significantly greater in fetuses with abnormal ACV. In 34 out of 156 cases (22%), chromosomal abnormalities were found. Twenty-three chromosomopathies out of 33 (70%) had an abnormal ACV, and 10 (30%) had a normal ACV. A significant association between abnormal karyotype and abnormal ACV was found. Ductus venosus measurement was carried out in 174 fetuses of group B. In 1 case, it was not possible to obtain the measurement. One hundred and seventy-one (99%) cases had a normal ACV, and in 2 (1%) cases the ACV was abnormal. No chromosomal abnormalities were found in group B. Considering group A and group B, a significant association between the finding of an enlarged NT and abnormal ACV was detected (p < 0.05). CONCLUSIONS: An abnormal ACV is more frequent in fetuses presenting enlarged NT than in those having normal NTs and in fetuses having the larger nuchal thickness. The probability of having a chromosomal abnormality in fetuses with enlarged NT is greater when an abnormal ACV is found.     

Outcome of fetuses with increased nuchal translucency

Recent reports on nuchal translucency screening in unselected patient populations show results that are comparable with those reported by the thus far largest series on screening for Down's syndrome based on maternal age and nuchal translucency measurement. Much interest is focused on the prognostic value of increased nuchal translucency in fetuses with normal chromosomes. Increased nuchal translucency is regarded as a clear sign of declining fetal health, which can be associated with fetal demise, structural anomalies, rare genetic syndromes, and in particular congenital heart defects. A clear association is demonstrated between nuchal translucency above the 99th centile and congenital cardiac defects. Such a finding should prompt specialized echocardiography. However, on the whole the sensitivity of nuchal translucency screening is too low to consider this as the sole criterion to screen for critical heart defects.