Increased nuchal translucency seems to be a well-established sonographic marker for aneuploidy screening, particularly when it is measured at an early gestational age. However, studies of its efficacy have yielded widely conflicting results, with detection rates ranging from 30% to 90% at the same 5% false-positive rate. Interestingly, a review of the current literature pertaining to nuchal markers suggests that the greater the experience of the group in nuchal translucency measurement, the better the results for prediction of aneuploidies. Current widespread application of first-trimester ultrasonography has enabled accumulation of an increasing body of knowledge pertaining to early screening for fetal aneuploidy. Following the initial reports,1–3,9–14 including our own preliminary experience,5 recent studies of large populations of patients at both high or low risk for chromosomal abnormalities demonstrate that increased nuchal translucency between 10 and 16 weeks' gestation by either transabdominal or transvaginal ultrasonography may serve as a screening tool for fetal aneuploidy.4,6,15–18
In our study, early second trimester nuchal translucency measurement can achieve prenatal detection rates of trisomy 21 in excess of 95% at a 5% false-positive rate. The overall detection rate in our center is considerably higher than in other studies. Several factors can contribute to this fact: First, the study is carried out in a single private tertiary-level ultrasound center, following strict methodological criteria in nuchal translucency measurements (well-trained experienced operators, our own nomograms established in a population of more than 10,000 chromosomally normal fetuses, optimal repeatibility). Second, the timing of measurements was optimal in most cases (67% of patients were scanned at 10–13 weeks' gestation). Finally, the distribution of chromosomal abnormalities in this study was such that 72/118 cases were common autosomal trisomies. Interestingly, the performance of this screening test is significantly better in the early gestational period and when predicting autosomal trisomies, particularly trisomy 21. We emphasize that, at the same 5% false-positive rate, the detection rate for trisomy 21 rises to 100% when nuchal translucency is measured at the early gestational period (at 10–14 weeks' gestation) but decreases to 56% at 15 and 16 weeks' gestation. In other studies including different gestational periods, detection rates were similar, and the contribution of nuchal markers decreased as the gestational age increased.13,19,20 Our results are consistent with the suggested transient appearance of nuchal translucency, which constitutes the main reason for selecting this particular gestational period for screening purposes. The pattern of chromosomal defects associated with increased nuchal translucency is similar to that observed in other studies,1,14 which confirms the value of this marker in the screening of the most common chromosomal anomalies, particularly trisomy 21.
Obviously, this screening test is more accurate when performed by experienced operators following strict methodological criteria and when measured at early second trimester. Methodological aspects related to training must be seriously considered in nuchal translucency implementation programs, to validate this strategy as a standard method in routine clinical practice. As with any new technology, it is essential that those undertaking the 10–16-week scan are adequately trained and that those results are subject to rigorous audit. Concerning the optimal gestational period, it is important to move screening strategies to earlier gestational ages because they have better performance during this period, and there are obvious advantages of an earlier prenatal diagnosis.
Two main questions remain to be answered concerning the issue of early prenatal screening of aneuploidies. First, what is the cost-effectiveness of adding other markers, such as maternal serum biochemistry or other sonographic and Doppler parameters? Second, what is the cost-effectiveness of a sequential approach combining first-trimester sonographic parameters and second-trimester biochemistry, knowing that first-trimester screening reduces the prevalence and the predictive value of maternal serum screening?21,22
Fetal nuchal translucency thickness at 10–14-week scan has been combined with maternal age to provide an effective method of screening for trisomy 21, achieving a detection rate about 70–80% at a 5% false-positive rate.1–3 When maternal serum biochemistry is also taken into account, the detection rate may rise to 90%.15 Recently, Doppler parameters have been suggested to improve the test performance in fetal aneuploidy screening. Increased impedance to flow in the umbilical artery,23–27 abnormal fetal heart rate,28–30 and abnormal ductus venosus flow31–35 have been described as potential markers of chromosomal abnormalities, although with variable results in the literature. But this prospective study in an unselected population demonstrates that a single simple standarized strategy, the nuchal translucency measurement, might achieve at least the same effectiveness. With such a high detection rate, the benefits of other additional markers may be less than previously thought.
On the other hand, a new proposed “integrated” approach using a panel of first- and second-trimester markers suggests that further improvement in the screening performance is possible, achieving a detection rate of 94% at a 5% false-positive rate.4,36–38 The sequential use of modalities with intermediate disclosure can be more practical but will generate a higher false-positive rate. Moreover, complex statistical modeling is needed to predict screening detection and false-positive rates for policies using different marker combinations and screening modalities, once we have demonstrated that they are statistically independent. Although better performance can be achieved by adding other independent markers or using a sequential first- and second-trimester policy, the high detection rate of trisomy 21 fetuses by using nuchal translucency as a single strategy suggests that early nuchal translucency measurement at 10–14 weeks' gestation can be a simple screening strategy to detect this condition. Combined strategies might be useful when nuchal translucency measurement can not be implemented properly, when there are no economic restrictions in the screening policy, or in selected high-risk groups.
Although there is debate on issues involving the choice between first and second trimester, biochemistry or sonographic parameters, single or combined strategies, research or standard of care, we can state that nuchal translucency is the most effective single screening test for trisomy 21. Early second trimester nuchal translucency measurement can achieve prenatal detection rates of Down syndrome in excess of 95% at a 5% false-positive rate. No other screening test can detect such a proportion of affected pregnancies with such a low false-positive rate. If current trends continue, it is likely that the early scan for nuchal translucency measurement will become a routine component of antenatal care. Moreover, increased nuchal translucency can also identify a high proportion of other chromosomal abnormalities and is associated with major heart defects, a wide range of skeletal dysplasias, and genetic syndromes. Other benefits of the early scan include early diagnosis of major fetal defects and the detection of multiple pregnancies, as well as reliable identification of chorionicity. Therefore, it is imperative to standarize the implementation of nuchal translucency programs, the best cost-effective screening strategy for Down syndrome.
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