Combination Of Nuchal Translucency Research Articles

First trimester screening with biochemical markers and ultrasound in relation to non-invasive prenatal testing (NIPT).

Non-invasive prenatal testing (NIPT) is often erroneously received as a diagnostic procedure due to its high discriminatory power in the field of fetal trisomy 21 diagnosis (wording: "NIPT replaces amniocentesis"). Already a look at the methodology of NIPT (statistical gene dose comparison of a primarily maternofetal DNA mixture information at selected sites of the genome) easily reveals that NIPT cannot match the gold standard offered by cytogenetic and molecular genetic analysis procedures from the matrix of the entire human genome (origin: vital fetal cells), neither in diagnostic breadth nor in diagnostic depth. In fact, NIPT in fetal medicine in its current stage of development is a selective genetic search procedure, which can be applied in primary (without indication) or secondary (indication-related) screening. Thus, NIPT competes with established search procedures for this field. Here, the combined nuchal translucency (NT) test according to Nicolaides has become the worldwide standard since 2000. The strength of this procedure is its broad predictive power: NT addresses not only the area of genetics, but also the statistically 10 times more frequent structural fetal defects. Thus, NIPT and NT have large overlaps with each other in the field of classical cytogenetics, with slightly different weighting in the fine consideration. However, NIPT without a systematic accompanying ultrasound examination would mean a step back to the prenatal care level of the 1980s. In this respect, additional fine ultrasound should always be required in the professional application of NIPT. NIPT can thus complement NT in wide areas, but not completely replace it.

The implementation of a combined nuchal translucency screening service

IntroductionCombined nuchal translucency (cNT) screening was established within a 3000 delivery unit at a cost of £18000. The uptake, changes in sensitivity and specificity and effect on the rate of...

A case report of a complex corpus callosal abnormality using advanced sonographic techniques

Mrs K P, a 29 year old P0G1 who presented at 12 weeks gestation for routine antenatal care. Aneuploidy screen revealed that her composite risk for Down's syndrome using a combination of nuchal translucency (measurement was 1.1mm), nasal bone assessment and biochemistry was low. Her blood group was O positive and screening tests for syphilis, rubella and HIV were negative. There was no family history of genetic or congenital anomalies. The rest of the antenatal care until 22 weeks was uneventful.

P11.18: Impact of ductus venosus assessment in screening Down syndrome protocols

Screening by combination of nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta hCG) and pregnancy-associated plasma protein-A (PAPP-A) is an effective strategy to detect Down syndrome. Our objective is to estimate the improvement in screening efficiency when ductus venosus (DV) Doppler studies are added to existing Down syndrome (DS) screening protocols. First-trimester combined screening for DS was prospectively carried out, from February 2007 to January 2009, in 4408 singleton pregnancies at 11 + 0 to 13 + 6 gestational weeks, including maternal age, biochemistry (beta hCG and PAPP-A) and nuchal translucency. Ductus venosus pulsatility index for veins was calculated at the same time. The maternal serum biochemistry was measured using the Kryptor analyzer (Brahms Diagnostica) in a two-step strategy. The detection rate (DR) and false-positive rates (FPR) for standard screening strategy (maternal age, NT and biochemistry) and the same strategy but including DV assessment were calculated. The mean maternal age was 33 (range 18–46) years. The mean gestation age at blood test was 71 (+/− 10) days. The mean gestation age at scan was 12,6 (range 10,5–13.6) weeks. The population included 35,8% over 35 years. Down syndrome was identified in 16 pregnancies. At a fixed 1% FPR, the DR for trisomy 21 at screening time was 68,8% for standard screening strategy and 81,3% when including DV assessment, respectively. Compared to the standard DS screening strategies, DV assessment can improve screening efficiency by significantly reducing the false-positive rate. Early evaluation of DV can be introduced to standard DS screening strategies in experienced centers as a first level screening test to reduce invasive test rate derived from the extended existing DS screening protocols.

Estudo da translucência nucal, ducto venoso, osso nasal e idade materna na detecção de cromossomopatia fetal em uma população de alto risco

OBJETIVO: Avaliar a translucência nucal, o ducto venoso, o osso nasal e a idade materna > 35 anos como testes de rastreamento para aneuploidias entre 12 e 14 semanas de gestação em pacientes de alto risco. MATERIAIS E MÉTODOS: Estudo prospectivo observacional envolvendo 92 gestantes entre 12 e 14 semanas submetidas a biópsia de vilo corial por alto risco de trissomia, baseado na medida da translucência nucal (17,4%) e idade materna >35 anos (78,3%). Antes da biópsia de vilo corial, realizaram-se medida da translucência nucal, avaliação de fluxo no ducto venoso e identificação do osso nasal. Calcularam-se a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo para testes realizados em paralelo e em seqüência. RESULTADOS: Encontrou-se alteração cromossômica em 12 (13,5%) fetos; 7 (58,3%) apresentavam trissomia 21. Osso nasal foi identificado em todos os fetos com trissomia. Translucência nucal, ducto venoso e idade materna isolados mostraram baixa sensibilidade (41,67-58,33%) e baixo valor preditivo positivo (10-45,45%). A associação translucência nucal + ducto venoso + idade materna apresentou o melhor resultado (sensibilidade: 100%; especificidade: 6,49%; valor preditivo positivo: 14,29%; valor preditivo negayivo: 100%). CONCLUSÃO: Em gestantes com idade > 35 anos, a associação translucência nucal + ducto venoso mostra-se como a mais sensível para a indicação de procedimento invasivo.

The Use of Nuchal Translucency in Contemporary Obstetric Practice

Nuchal translucency sonography is the most powerful single prenatal marker for Down syndrome. Its detection rate is 75% at a 5% false-positive rate. The combination of nuchal translucency and maternal serum-free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A can identify 85% to 90% of fetuses with Down syndrome for a false-positive rate of 5%. This method can also identify more than 90% of fetuses with trisomies 18 and 13, Turner syndrome, and triploidy for a screen-positive rate of 1%.

Prospective audit of a one-centre combined nuchal translucency and triple test programme for the detection of trisomy 21

To determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan. A prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 19-46). Women were offered NT screening at 11 to 14 weeks. Those with NT > or =3 mm were offered chorionic villus sampling. Those declining CVS, and those with NT <3 mm, were offered early triple tests. Women with a term combined risk of trisomy 21 > or = 1:250, based on age, NT, and triple test results were offered amniocentesis. Using a 3-mm NT 'cut-off' identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9). Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%) had a > or = 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to achieve an 88% detection rate using the triple test alone, the predicted FPR would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the detection rate would be only 60%. In a high-risk group, the combination of NT with triple test offers detection of trisomy 21 at least equivalent to either test, while allowing disclosure of an abnormal NT at the scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably lower than expected for triple test alone for this population.

The best marker combination using the integrated screening test approach for detecting various chromosomal aneuploidies

To evaluate the cross-trimester multiple marker correlation and the minimum marker combination needed for detecting various chromosomal aneuploidies. Parturient women with singleton pregnancies who underwent non-interventional sequential screening test and followed prospectively were recruited. They all underwent first trimester combined nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (f-betahCG), followed by second trimester measurement of unconjugated estriol (uE3), human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). Pearson correlation was applied to compute any cross-trimester marker correlation and logistic regression analysis was used to determine the minimum marker combination for detecting various categories of chromosomal aneuploidies. The current study included 552 normal and 43 chromosomal-affected pregnancies (24 Down's syndrome [DS], 7 Turner's syndrome, 8 Edward's syndrome, 4 Klinefelter syndrome and 5 triploidy) for which the results of both the screening tests and the pregnancy outcome were available. In the normal cases, a significant correlation was found between f-betahCG and hCG (r=0.52), as well as between PAPP-A and uE3 (r=0.174). In DS pregnancies, the NT correlated with both hCG (r=0.45) and uE3 (r=-0.39). In Turner's syndrome, uE3 correlated both with PAPP-A (r=0.97) and f-betahCG (r=0.97). No other significant correlations were found. Furthermore, with the exception of f-betahCG and hCG in the unaffected cases, all other markers correlation appeared very weak. For detecting all the above categories of aneuploidies, the combination of NT, PAPP-A and uE3 and the maternal age background risk were found adequate, with a 74% detection rate (DR) for a 5% false positive rate (FPR). For DS only, the combination of maternal age-related background risk and the combination of NT, PAPP-A, hCG and AFP yielded a 79% DR for a 5% FPR. The current study agrees with a previous report that, overall, there is no strong correlation between first and second trimester markers. The extension of the integrated test for detecting various categories of common chromosomal aneuploidies using NT, PAPP-A and uE3 deserves further evaluation.

Expectation and knowledge of women undergoing first-trimester combined screening for Down syndrome in a Chinese population

To study the preference of pregnant women regarding the time taken to report the results of first-trimester combined screening for Down syndrome and their knowledge about it. A questionnaire survey was conducted on a cohort of 325 pregnant participants who attended our first-trimester combined nuchal translucency and biochemical screening programme for fetal Down syndrome. This service was operated in a one-stop setting and the result of the screening test was available within 1 to 2 h after the collection of blood sample. The majority of participants: (1) could recall the quoted detection rate correctly (96.6%); (2) understood that a negative test does not exclude Down syndrome (91.1%); (3) understood that a positive test does not equate to an affected fetus (91.0%), and (4) could decide on the need for further invasive tests on the basis of the screening test results (98.1%). Twenty-nine percent of participants considered that a one-stop setting was very important because any delay in releasing the results made a significant difference to them, while 48.9% considered it acceptable if the results were available on the same day. The percentage dropped dramatically to 6.3% (within 2 days), 6.7% (within 3 days), 5.7% (within 1 week), and 3.1% (more than 1 week). The majority of the pregnant women in our test considered same day reporting of screening test results to be no different from a one-stop clinic. This would have important implications for the organisation and structuring of our service provision, since the operation of a one-stop clinic imposes significant stresses on the clinical staff involved.

The cost effectiveness of prenatal ultrasound screening for trisomy 21

The cost-effectiveness of opportunistic nuchal translucency ultrasound screening in pregnancy was compared with alternative screening strategies for trisomy 21 in Australia. A decision analytic model was used of various pregnancy screening strategies based on a systematic review of the literature on the effectiveness of nuchal translucency ultrasound and serum screening and costs based on current reimbursement fees. The model included the likelihood and cost of terminations after diagnostic testing and the associated risk of fetal loss. All prices are in 2001 Australian dollars. With a twenty percentage point difference in detection rate, the incremental cost for a combination of nuchal translucency and serum screening with age in the first trimester compared with maternal serum screening in the second trimester was 105,484 dollars per extra case detected and 374,779 dollars per live trisomy 21 birth avoided. Serum screening in the second trimester had an incremental cost per extra case detected of between 61,700 dollars and 117,100 dollars per extra live birth avoided when compared with no screening. The cost-effectiveness of ultrasound screening for trisomy 21 would appear to be more attractive if it were done at the same time as current dating ultrasound. Any funding mechanism for screening should take this strategy into account by incorporating, as far as possible, provision of nuchal translucency screening into existing services provided in early pregnancy.

Nuchal translucence incorporated into a one-stage multifactorial screening model for Down syndrome prediction at second-trimester pregnancy

The aim of this study was to achieve one-stage screening for trisomy 21 using a combination of nuchal translucency ( NuT) measurement and maternal serum alpha-fetoprotein (AFP) and free β-human chorionic gonadotrophin (hCG) biochemistry levels in the second trimester among a high-risk study population. From January 1998 to June 2001, 45 cases of trisomy 21 were prenatally found and confirmed in the hospital-based cytogenetic diagnosis laboratory. A total of 867 normal singleton pregnancies were enrolled as controls from the antenatal care clinics in the hospital. All study and control subjects between 13 weeks and 18 weeks of gestation with a mean age of 15.2 ± 1.3 weeks underwent one-stage nuchal translucence measurements and maternal serum biochemical screening for Down syndrome. The final logistic model contained β-hCG (multiples of the gestational median or MoM), maternal age ( matA), nuchal translucence ( NuT MoM) and AFP (MoM) as covariates. Also, the estimated coefficients of the regression were highly significant. This model provided the estimated probability of Down syndrome as follows: Pr (Down syndrome) = exp ( Z )/ [1 + exp ( Z )], where Z = −11.18 + 0.64 × (β-hCG MoM) + 0.25 × matA + 1.32 × NuT MoM −2.23 × AFP MoM. The logistic regression with estimated coefficients was installed in a Palm digital assistant (PDA) equipped with Excel® (Microsoft). The risk probability of Down syndrome could be readily calculated after inputting data for all four predictor variables. (E-mail: jhhung@vghtpe.gov.tw)

First-trimester screening for aneuploidy with fetal nuchal translucency in a United States population.

To examine the detection rate of chromosomal abnormalities using a combination of nuchal translucency (NT) and maternal age in a United States population. A total of 2131 pregnancies with 2339 fetuses underwent NT screening from April 2000 to April 2002 in our ultrasound unit. Nuchal translucency was measured from 11 to 14 weeks' gestation. Fetal crown-rump length (CRL) was also measured. The risk for trisomy 21 was calculated from a combination of maternal age and fetal NT with the use of software provided by The Fetal Medicine Foundation (FMF). Sensitivity and false-positive rates were calculated for different risk cut-offs. Chromosomal defects were diagnosed in 32 cases, including 12 cases of trisomy 21 and 10 cases of trisomy 18. The estimated risk based on maternal age and fetal NT was 1 in 300 or greater in 195 (8.3%) cases and these included 10/12 (83.3%) pregnancies with trisomy 21 and 9/10 (90.0%) pregnancies with trisomy 18. A combination of maternal age and fetal NT provides an effective method of screening for chromosomal defects. Using ultrasound techniques and risk algorithms from The FMF, the performance of the test in an American population is similar to that described in international populations.

Nuchal translucency screening and antenatal maternal serum screening for Down syndrome: results of a project

Objectives: To asses the implementation of antenatal screening for Down syndrome using individual risk estimates based on maternal age, nuchal translucency and three serum markers; alpha fetoprotein, unconjugated estriol and human chorionic gonadotrophin (hCG) in maternal blood. Women with an estimated risk of 1 in 250 or greater were classified as screen positive and offered diagnostic amniocentesis.Subjects: A total of 1956 women of all ages with singleton pregnancies seen between June 1999 and March 2001.Results: The screening result of combination of first trimester ultrasonographic and serum screening was 85% Down syndrome detection and the false positive rate was 3%. The median gestational age of nuchal translucency was 11 weeks and the time of serum screening was 16 weeks.Conclusion: The combination of nuchal translucency and serum screening increases the Down syndrome detection and decreases the false positive rate. Is very important because the amniocentesis is associated with a risk of pregnancy loss from 0.5 to 1%. Besides, it is cost‐effective and performs better than the selection for amniocentesis on the basis of maternal age only, nuchal translucency only or serum screening.

Sonographic screening for fetal aneuploidy: first trimester.

Screening for fetal aneuploidy is now possible during the first trimester using sonographic and biochemical markers. The aim of this review was to summarize the efficacy and use of nuchal translucency in screening for fetal aneuploidy, especially fetal Down syndrome, and other anomalies. We reviewed available literature regarding first-trimester screening. This includes more than 16 studies of nuchal translucency as a marker for fetal aneuploidy published since 1995. Although early studies showed wide variation in detection of fetal Down syndrome when using nuchal translucency, more recent studies showed sensitivities of approximately 70% to 80%, for a 5% false-positive rate. Increased nuchal translucency has also been found to be a marker for other aneuploidies, including trisomy 18, trisomy 13, and Turner syndrome. Maternal serum biochemical screening can be used as a test for aneuploidy during the first trimester The 2 maternal serum markers that appear to be most useful in the late first trimester are the free beta subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Together with maternal age, these markers yield a detection rate for trisomy 21 of approximately 60%, for a 5% false-positive rate. Because sonographic and biochemical markers appear to be largely independent, their combined risk results in improved detection rates compared with either method alone. As a result, the combination of nuchal translucency, biochemical markers, and maternal age has achieved a detection rate of approximately 85%, for a 5% false-positive level for detection of trisomy 21. A newly proposed "integrated" approach using a panel of first- and second-trimester markers suggests that further improvement in the screening performance is possible. A number of questions regarding first-trimester screening remain. We address some of these questions: is first-trimester screening more effective than second-trimester screening? How to account for intrauterine lethality? Is earlier diagnosis important, and will it be accepted by patients? Is first-trimester screening cost-effective? How should first-trimester screening be interpreted with second-trimester tests? Despite encouraging data and general enthusiasm for first-trimester screening for fetal Down syndrome and other aneuploidies, a number of questions remain about its implementation in the United States. Multicenter studies currently under way should help answer some of these questions.

First-Trimester Down Syndrome Screening Using Dried Blood Biochemistry and Nuchal Translucency

In Brief Objective To assess the effectiveness of free β-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18. Methods Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the combination of nuchal translucency and biochemistry (n = 5809). Results The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15.8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0.9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%. Conclusion First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients. First-trimester screening for Down syndrome and trisomy 18 is effective and results in identification of a high yield of affected cases for each diagnostic procedure done.

First-Trimester down syndrome screening using dried blood biochemistry and nuchal translucency

Objective: To assess the effectiveness of free β-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18. Methods: Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only ( n = 10,251), nuchal translucency only ( n = 5809), and the combination of nuchal translucency and biochemistry ( n = 5809). Results: The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15.8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0.9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%. Conclusion: First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients.