Trimester Nuchal Translucency Measurement Research Articles

Testing for Noonan syndrome after increased nuchal translucency.

The aim of this study was to report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. This is a retrospective chart review. (1) first trimester NT measurement ≥3mm, (2) normal karyotype by either a CVS or an amniocentesis procedure, and (3) prenatal molecular genetic testing for NS completed. Results with known pathogenic variants were considered positive, while those with variants of unknown clinical significance, or with no variants, were considered negative. A total of 804 fetuses had an NT measurement of ≥3mm, with a median NT thickness of 3.6mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3mm were not tested for NS (p=0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. In euploid fetuses, increased NT is associated with a 10% risk of NS. © 2017 John Wiley & Sons, Ltd.

Analyse du parcours de dépistage prénatal des femmes ayant donné naissance en France à un enfant atteint de trisomie 21

ObjectiveThe main objective of this study was to screen the prenatal follow-up of women with live birth trisomy 21 child in order to evaluate the proportion of prenatal screening failure versus cases where the women refused either the screening or the prenatal diagnosis of Down syndrome. This study covers the period of time from 2009 to 2012 when the national prenatal screening policy changed from second to first trimester and allows for a comparative assessment of the nationwide efficiency of the various maternal serum marker based strategies. MethodAll authorized cytogenetic laboratories sent required data for all cases of trisomy 21 diagnosed in FRANCE in new-borns (less than 1-year-old) from January 2010 to July 2013. ResultsA total of 1253 cases of trisomy 21 were diagnosed before 1 year of age whose mother did not had prenatal diagnosis. For 861 of them, information on the prenatal follow-up was available, with 72% of cases where a prenatal screening was organized either by maternal serum marker or by ultrasound. Results of the screening strategy was positive with maternal serum marker in 28% of cases (calculated risk≥1/250), positive because of abnormal ultrasound in 5% and negative with maternal marker screening (whatever the strategy used) in 67% of cases. Detection rate over the period of the study was 82%, with similar efficiency of first and second trimester strategies (83%) but significantly lower with sequential association of first trimester Nuchal translucency measurement and second trimester serum screening (70%). ConclusionSwitching from second trimester to first trimester screening strategy, with as many trisomy 21 foetuses diagnosed with half invasive procedures fulfilled national health policy objectives. Analysis of these data gives useful insights to elaborate a future screening policy involving cell-free foetal DNA sequencing.

Extremely large nuchal translucency measurement predicts adverse pregnancy outcome

A prospective study was conducted to determine the outcome of pregnancies with 1st trimester nuchal translucency measurement of ≥ 6.5 mm. The risk of fetal abnormalities increases with enlarging nuchal translucency, being around 45% with a measurement of ≥ 6.5 mm. A total of 27,144 women with singleton pregnancies participated in the combined Down syndrome screening within the public healthcare system in Northern Finland. The study period was 1 May 2002 to 31 May 2009. The nuchal translucency measurement was ≥ 6.5 mm in 16 cases (0.06%). Pregnancy outcome was normal in one case (6.3%). The risk of abnormality was higher in our study than reported in the literature. According to our study, immediate diagnostic tests should be offered after an nuchal translucency measurement of ≥ 6.5 mm. We should also consider analysis of fetal micro-deletions associated with certain syndromes.

Is there any relationship between adverse pregnancy outcome and first trimester nuchal translucency measurements in normal karyotype fetuses?

Aim: This study aims to research whether there is a relationship between first trimester nuchal translucency (NT) measurements and pregnancy complications such as gestational diabetes mellitus (GDM), gestational hypertension (GHT), intrauterine growth restriction (IUGR) and oligohydramnios.Method: This study included 225 singleton pregnancies attending Canakkale Onsekiz Mart University Obstetrics and Gynecology clinic for all monitoring and examinations, and gave birth at our clinic between January 2011 and December 2012. Data sources were clinical records and the hospital's automation system, and the study was planned as retrospective cohort. NT measurement was made between 10 weeks 3 days and 13 weeks 6 days gestation. For data analysis, the chi-square, Mann–Whitney U test and Spearman correlation were used.Results: Of pregnancies, in the study, 5 (2.2%) developed GDM, 6 (2.6%) developed GHT, 2 (0.89%) developed IUGR and 10 (4.4%) developed oligohydramnios. There was no correlation identified between NT measurements and development of GDM, GHT, IUGR and oligohydramnios.Conclusion: There was no relationship found between first trimester NT measurements and complications that could develop in pregnancy. For the first time in the literature, NT and oligohydramnios were studied and no relationship was observed.

OP12.01: Low sensitivity in screening for congenital heart diseases by nuchal translucency in a low risk population of 102,472 pregnancies

Objectives: In Flanders (the Dutch speaking Northern part of Belgium) the prenatal detection rate of congenital heart diseases (CHD) is very low. The primary goal of this retrospective study is to determine the sensitivity, positive and negative predictive value (PPV and NPV) of nuchal translucency (NT) measurement for prenatal CHD diagnosis in a general low risk population and to consider if NT measurement is an effective screening tool for CHD. Methods: We used the registry of the General Medical Laboratory, handling the largest percentage of maternal serum samples for first trimester aneuploidy screening in Flanders, to select those fetuses with an enlarged NT. The outcome of these pregnancies was collected from the referring gynecologists and ultrasonographers. Results: In 102,472 maternal serum samples over a 9 years period, 303 (0.30%) pregnancies, had -at least onefetus with a NT of ≥3.5 mm. 156 fetuses were suitable for analysis. In this group the overall incidence of CHD was 7.7% in fetuses with a normal karyotype. The sensitivity for CHD in the group with a NT of ≥3.5 mm and normal fetal karyotype is 1.9% with a specificity of 99.9%, positive predictive value of 7.1% and negative predictive value of 99.4%. The false positive rate is 0.14%. The false negative rate is 98.1%. The likelihood ratio is 13.6. Conclusions: Low sensitivity and high false negative rate make first trimester NT measurement not an effective screening tool for CHD detection at population level.

Serum PAPP-A Levels at 10–14 Weeks of Gestation Are Altered in Women After Assisted Conception

The most sensitive and specific first-trimester Down syndrome screening test employs a combination of maternal age, nuchal translucency (NT) thickness, fβhCG, and PAPP-A. First trimester NT measurements do not differ significantly between pregnancies resulting from assisted reproductive technology (ART) and those resulting from spontaneous conception, but maternal blood levels of free beta human chorionic gonadotropin (fβhCG) are higher following in vitro fertilization-embryo transfer (IVF-ET), and levels of pregnancy-associated plasma protein-A (PAPP-A) are lower. Whether or not this results in a higher rate of false positive screening test results is controversial. The investigators compared the screen-positive rates of the first trimester Down syndrome screening test in women with singleton ART pregnancies to those of women whose pregnancies resulted from spontaneous conception. Participants included 130 women who were pregnant after IVF-ET (group 1); 54 who conceived after intracytoplasmic sperm injection (ISCI; group 2); and 914 control women who conceived spontaneously. Fetal NT thickness was estimated at 10–14 weeks’ gestation. Women who conceived via ICSI were 2.8 times as more likely to be screen positive than control women. Although ovarian stimulation in group 1 and group 2 women was associated with significantly lower PAPP-A levels than were present in the control group, women who conceived via IVF-ET were not more likely to be screen positive than control women. Levels of PAPP-A declined significantly as the number of retrieved oocytes or transferred embryos increased, but the levels of other markers were not affected. When a single embryo was transferred, or when ART conception occurred without ovarian stimulation, marker levels were similar to those following spontaneous conception. Although ICSI appears to be associated with a higher rate of false positive first trimester screening test results than that in spontaneously conceived pregnancies, women who conceive by other ART methods are not at increased risk.

Elevated first-trimester nuchal translucency increases the risk of congenital heart defects

We sought to evaluate the association between first trimester nuchal translucency measurement and the risk for major congenital heart defect in chromosomally normal fetuses. First trimester (10 weeks 4 days of gestation to 13 weeks 6 days of gestation) nuchal translucency was obtained in a large prospective multicenter National Institute of Child Health and Human Development study for Down syndrome prediction. The study, which was conducted between May 1998 and December 2000, was restricted to singleton pregnancies. Gestational age was determined by crown rump length measurements. Perinatal outcomes were determined and included the frequency of major congenital heart defect, which was defined as those cases that potentially could require surgery, intensive medical therapy, or prolonged follow-up time. Logistic regression analysis was used to determine whether nuchal translucency was a significant predictor of congenital heart defect. There were 8167 chromosomally normal pregnancies, of which 21 cases of major congenital heart defect were identified at follow-up examination (incidence, 2.6/1000 pregnancies). The risk of congenital heart defect rose with increasing nuchal translucency measurements. The mean nuchal translucency value for the normal and congenital heart defect groups were 1.5 mm and 1.9 mm, respectively (P = .05). With a nuchal translucency measurement of < 2.0 mm, the incidence of congenital heart defect was 13 of 6757 pregnancies (1.9 of every 1000 pregnancies). At 2.0 to 2.4 mm, the incidence was 5 of 1032 pregnancies (4.8 of every 1000 pregnancies). At 2.5 to 3.4 mm, the incidence was 2 of 335 pregnancies (6.0 of every 1000 pregnancies). At > or = 3.5 mm, the incidence was 1 of 43 pregnancies (23 of every 1000 pregnancies). Logistic regression analysis confirmed that nuchal translucency was associated significantly with congenital heart defect (odds ratio, 2.1; 95% CI, 1.4-3.1; P = .0004). Increased first trimester nuchal translucency measurement was associated with a higher risk of major congenital heart defect in chromosomally normal pregnancies. The practical implications of our findings are that patients with unexplained elevations of nuchal translucency may need referral for a fetal echocardiogram.

Measurement of Nuchal Translucency as a Single Strategy in Trisomy 21 Screening

In Brief OBJECTIVE To evaluate the role of nuchal translucency thickness as a single marker in screening for trisomy 21 at 10–16 weeks' gestation. METHODS From December 1996 to October 2001, nuchal translucency was measured in 11,281 consecutive early second trimester fetuses referred to our unit for prenatal care and delivery. Scans were performed by eight experienced ultrasonographers, under strict methodological criteria. RESULTS Chromosomal abnormalities were found in 118 cases (52 trisomy 21). Using nuchal translucency greater than the 95th centile as a cut-off, the overall detection rate was 71.2% with a specificity of 95.4%, and a positive predictive value of 14%. In the trisomy 21 selected group, detection rate, specificity, and positive predictive value for nuchal translucency were 92.3%, 95.4%, and 8.5%, respectively. The detection rate of trisomy 21 reached 100% when nuchal translucency was measured between 10 and 14 weeks' gestation, maintaining the same specificity. CONCLUSION Early second trimester nuchal translucency measurement can achieve prenatal detection rates of trisomy 21 greater than 95% with a 5% false-positive rate. With a detection rate so high, the benefits of using additional markers may be less than previously considered. Although maternal age, other sonographic or Doppler markers, and maternal serum biochemistry might play a role in prenatal strategies to detect fetal chromosomal abnormalities, the high detection rate of trisomy 21 fetuses using nuchal translucency as a single parameter suggests that early nuchal translucency measurement between 10 and 14 weeks' gestation can be a simple screening strategy for this condition. Early second-trimester nuchal measurement can be a simple screening strategy to detect fetal trisomy 21.

Measurement of nuchal translucency as a single strategy in trisomy 21 screening: should we use any other marker?

OBJECTIVE:To evaluate the role of nuchal translucency thickness as a single marker in screening for trisomy 21 at 10–16 weeks’ gestation.METHODS:From December 1996 to October 2001, nuchal translucency was measured in 11,281 consecutive early second trimester fetuses referred to our unit for prenatal care and delivery. Scans were performed by eight experienced ultrasonographers, under strict methodological criteria.RESULTS:Chromosomal abnormalities were found in 118 cases (52 trisomy 21). Using nuchal translucency greater than the 95th centile as a cut-off, the overall detection rate was 71.2% with a specificity of 95.4%, and a positive predictive value of 14%. In the trisomy 21 selected group, detection rate, specificity, and positive predictive value for nuchal translucency were 92.3%, 95.4%, and 8.5%, respectively. The detection rate of trisomy 21 reached 100% when nuchal translucency was measured between 10 and 14 weeks’ gestation, maintaining the same specificity.CONCLUSION:Early second trimester nuchal translucency measurement can achieve prenatal detection rates of trisomy 21 greater than 95% with a 5% false-positive rate. With a detection rate so high, the benefits of using additional markers may be less than previously considered. Although maternal age, other sonographic or Doppler markers, and maternal serum biochemistry might play a role in prenatal strategies to detect fetal chromosomal abnormalities, the high detection rate of trisomy 21 fetuses using nuchal translucency as a single parameter suggests that early nuchal translucency measurement between 10 and 14 weeks’ gestation can be a simple screening strategy for this condition.

Screening for aneuploidy by first trimester nuchal translucency measurement: results from a prospective trial including 1980 cases in a single center in Switzerland

The purpose of this study was to evaluate the efficiency of first trimester screening for chromosomal abnormalities using the sonographically determined thickness of nuchal translucency (NT) combined with maternal age. Risk screening was offered to all patients with a fetal crown rump length (CRL) between 45 and 84 mm after extensive counselling. For the risk assessment the software provided by the Fetal Medicine Foundation was used. In accordance with the recommendation of the Swiss Working Group on First Trimester Screening a cut-off risk of 1 : 400 was chosen. A total of 1980 consecutive pregnancies participating in the risk screening programme with due dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522 (26.4 %) patients were 35 yrs or older. A positive risk screening result was obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %) cases with unbalanced chromosomal abnormalities. The detection rate for unbalanced chromosome abnormalities in general (89.2 %) as well as the one for trisomy 21 (93.3 %) in particular are very high with a moderate false-positive rate (9.6 %) in this series. As a comparison in the series presented here, traditional "maternal age screening" (cut-off age 35 yrs) would have yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and 73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false-positive rate by raising the cut-off age to 38 yrs would yield detection rates of 40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a false-positive rate of 8.9 %. The number of invasive procedures performed to detect one unbalanced chromosome count may be calculated as 21.75 using the cut-off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The outcome of this ongoing study is in good accordance with the earlier observation that the main benefit of the addition of first trimester NT measurements to the risk screening protocol is a very high detection rate at a moderate false-positive rate.

The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's syndrome.

To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. Retrospective five-year review. Maternity unit of a university hospital. An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were > or = 37 years old. A subgroup (n = 4,864) also had second trimester biochemical testing by alpha-fetoprotein and free beta-human chorionic gonadotrophin. Prenatal and postnatal diagnosis of trisomy 21. Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester.

The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's Syndrome

Objective To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. Design Retrospective five-year review. Setting Maternity unit of a university hospital. Population An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were ≥ 37 years old. A subgroup ( n=4864) also had second trimester biochemical testing by alpha-fetoprotein and free β-human chorionic gonadotrophin. Main outcome measures Prenatal and postnatal diagnosis of trisomy 21. Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. Conclusion First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester.

Dépistage de la trisomie 21 : clarté nucale et/ou marqueurs sériques ?

Objectives – To compare alternative methods of antenatal screening for Down’s syndrome (nuchal translucency measurement and second trimester maternal serum screening) in a low-risk population and to evaluate the consequences of a sequential estimation of risk. Methods – In a consecutive series of 4308 women aged less than 38 with a singleton pregnancy, we examined the detection rate of nuchal translucency (NT) measurement at 10-14 weeks and maternal serum screening (MSS) by human chorionic gonadotropin and alpha-feto-protein at 14-18 weeks. Women with a NT measurement = 3 mm and women with a MSS derived risk =1/250 were recommended to have an amniocentesis. A second trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was entered in a computerized database and the detection rate and false-positive rate of different screening strategies were analysed. Results – Of the 4308 pregnancies that were followed (mean maternal age 30.1 years), there were 12 cases of Down’s syndrome (0.28 %), all detected prenatally. Seven of twelve cases had a NT measurement above 3 mm (58 %), and 6 out of ten cases with available MSS had a calculated risk =1/250 (60 %). Four of the five cases with NT measurement below 3 mm were detected by subsequent MSS. At a threshold giving 5 % of positive tests, the sensitivity of NT screening and MSS were 75 % and 60 %, respectively. Discussion and conclusion – Sequential screening for Down’s syndrome by nuchal translucency and second trimester biochemistry is effective and appears to increase the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of MSS derived risk should be combined to the first trimester NT measurement.

Ultrasonographic markers for chromosomal abnormalities in women with negative nuchal translucency and second trimester maternal serum biochemistry.

To analyze the value of second trimester ultrasound examination among those women whose fetuses were indicated to be at low risk of chromosomal anomalies on the basis of both first trimester nuchal translucency measurement and second trimester biochemical screening. A retrospective study of 5500 pregnancies carried out at the fetal medicine unit, Royal Free Hospital. During a period of over 3 years 5500 pregnancies underwent a first trimester scan and nuchal translucency measurement which enabled the detection of 62% (20 of 32) of all chromosomal anomalies. From the remaining pregnancies that underwent second trimester biochemical screening, 3548 were considered negative (risk < 1:250; using maternal serum free beta human chorionic gonadotrophin and alpha fetoprotein). The ultrasound markers that were examined were: shortened femur length, echogenic bowel, pyelectasis, choroid plexus cysts and echogenic intracardiac foci. The likelihood ratios for chromosomal aneuploides for each of these markers were calculated. Of the 3548 screen negative pregnancies, 3541 (99.8%) had a normal karyotype. Seven (0.2%) fetuses had an abnormal karyotype including four (0.11%) with trisomy 21, one with trisomy 18 and two with 47XXY. Second trimester ultrasound markers were found in two of the five (40%) with severe chromosomal anomalies compared to 184 of 3541 (5.2%) with normal karyotypes. Detection of one or more ultrasound markers in a screen negative pregnancy increased the possibility of chromosomal aneuploidy and a negative ultrasound decreased the risk by a likelihood ratio of 0.6 (95% confidence interval, 0.3-1.3). The risk was considerably increased when two or more markers were detected and we would recommend karyotyping under these circumstances. This preliminary data indicates a possible role for abnormal ultrasound markers in assessing the risk of chromosomal abnormalities in patients considered to be at low risk by nuchal translucency and serum screening. However analysis of a much larger study group will have to be conducted to assess the significance of individual markers.

First trimester nuchal translucency: effective routine screening for Down's syndrome.

The objective was to evaluate the effectiveness of 10-14 week nuchal translucency measurement in routine ultrasound screening for Down's syndrome. 11,398 women were scanned at 10-14 weeks of pregnancy for nuchal translucency measurements. The mean maternal age of the screened population was not significantly different from that of the booking population. A 5% screen positive rate was achieved by using a nuchal translucency-derived risk of > or = 1:200. Screening using this nuchal translucency risk would enable the first trimester detection of 16 out of 21 (76%) fetuses with Down's syndrome and 40 out of 49 (81%) aneuploid fetuses. In conclusion, this study demonstrates that first trimester nuchal translucency measurement is an effective method of screening for fetal chromosomal abnormality.

Effect of routine screening for Down's syndrome on the significance of isolated fetal hydronephrosis.

To determine the risk of Down's syndrome in fetuses with isolated hydronephrosis at 18-23 weeks in an unselected general population after routine screening for Down's syndrome, using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. All pregnant women undergoing a routine 18-23 week ultrasound scan, from a population who had been offered screening for Down's syndrome. A district general hospital serving a low risk obstetric population. Prospective study of all routine 18-23 weeks ultrasound scans. The prevalence of isolated hydronephrosis and Down's syndrome was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings. 10,971 women were scanned at 18-23 weeks during the study period. Down's syndrome was diagnosed in 14 of 20 cases before this stage using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. Isolated fetal hydronephrosis was diagnosed in 423 pregnancies (3.9%); none of these pregnancies were affected by Down's syndrome. The relative risk for Down's syndrome was 0.18 (95% CI 0.06-0.53) for women with a normal scan (n = 9983). When multiple ultrasound markers were found (n = 565), the relative risk for Down's syndrome was 2.00 (95% CI 0.18-22.10) and 9.00 (95% CI 1.14-71.30) for all other aneuploidies. The finding of isolated fetal hydronephrosis does not significantly increase the age-related risk for Down's syndrome. The presence of multiple ultrasound markers is associated with an increased risk of aneuploidies other than Down's syndiome. These findings are explained by the reduced prevalence of Down's syndrome as a result of prior screening and diagnosis of this condition.