Fetal Nasal Bone Assessment in First Trimester Down Syndrome Screening

Abstract

Objective: To evaluate the contribution of nasal bone assessment in the first trimester Down syndrome screening. Methods: The fetuses which underwent first trimester screening with nuchal translucency (NT) measurement were evaluated for the absence or presence of nasal bone according to the instructions described by the Fetal Medicine Foundation, London. Results: Among the 1,807 fetuses included in the study, 9 had trisomy 21. The detection rate of Down syndrome with NT measurement was 77.8% (7/9) with a false-positive rate of 4.5%. Incorporation of biochemical tests (PAPP-A, and free β-hCG measurement) into the screening increased the detection rate to 88.9% (8/9) and decreased the false-positive rate to 3.6%. The prevalence of absent nasal bone was 7/1,798 (0.39%) in chromosomally normal fetuses, and 3/9 (33.3%) in Down syndrome fetuses. Sensitivity, specificity, positive predictive and negative predictive values of absence of nasal bone for trisomy 21 are 33.3% (CI: 0.12–0.64), 99.6% (CI: 0.99–0.99), 30% (95% CI: 0.11–0.53) and 99.7% (95% CI: 0.99–0.99), respectively. The positive likelihood ratio of absent nasal bone was 85.6 (95% CI: 26.2–279.5), and the negative likelihood was 0.67 (95% CI: 0.42–1.06). When nasal bone assessment was incorporated into the NT risk assessment or combined test, the detection rate of trisomy 21 was not changed, however, the false-positive rate decreased to 3.4 and 3%, respectively. Conclusion: The absence of fetal nasal bone has a high positive likelihood ratio for Down syndrome in the first trimester screening, and the presence of nasal bone may potentially lower the need for invasive testing.

Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta‐analysis

“…Eight performed the test of NT alone, including 103 568 patients. Most of the studies (8/24) chose the cut‐off value of 1 in 300 as the positive result, six studies chose the cut‐off value of 1 in 250, three studies were 1 in 270, one was 2.5 mm, one was 95 th centile, one was 99 th centile and one used 1.5 MoM (multiples of the calculated regressed median), respectively. Most of the studies (21/24) were published in English, and the remaining three articles were published in Chinese.…”

“…One study interpreted that the result of the index tests was blinded to the reference tests result; the threshold was prespecified in all studies. Most studies (23/24) which the results of the index test influence the decision on whether to performance the reference standard may be subject to bias on estimating diagnostic accuracy, verification bias occurs studies (23/24)when only a proportion of the study group receives confirmation of the diagnosis by the reference standard . A potential bias exists in studies it is because that not all participants recruited into the studies were included in the analysis .…”

“…As the flow chart showed (Figure 1), our research yielded 126 citations, and 24 studies [11][12][13][14]18,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] were included in this systematic review eventually. The main reasons for exclusion by titles and abstract were duplicates among databases (n = 79), off-topic articles (n = 35), review articles (n = 8), other markers (n = 20) and other outcomes (n = 9).…”

Impact of First-Trimester Aneuploidy Screening in a High-Risk Population

“…The slightly greater detection rate of Down syndrome with contingent or sequential screening, compared to first-trimester screening, must be balanced by the potentially smaller fraction of women that will find these more complicated protocols acceptable; more women may elect to go straight to an invasive procedure or opt out of screening altogether. Increasing the detection rate in the first trimester, by utilizing nasal bone [12][13][14] or other criteria, may be a way out of this conundrum. The optimal screening test is not yet known, and may be different in different populations.…”

First Trimester Ultrasound Assessment for Fetal Aneuploidy

“…One of the attractions of the combination of these markers is that the test is more robust from a quality assurance perspective; the potential effects of consistent undermeasurement or overmeasurement of nuchal translucency, or of persistent miscalculation of biochemical MoMs, will be blunted by the use of multiple parameters. 28,[63][64][65][66][67][68][69][70][71][72][73][74][75][76] Although there is some association with gestational age, ethnic origin, and nuchal translucency thickness, this finding is uncommon in euploid fetuses and this is a very specific screening tool. The specificity of this test could, however, be improved by the addition of extra biochemical or ultrasound markers.…”