Improved diagnostic accuracy by using secondary ultrasound markers in the first‐trimester screening for trisomies 21, 18 and 13 and Turner syndrome

Objective: To evaluate the most common first-trimester ultrasound features of fetuses with trisomy 21 (T21) and to examine the screening performance for Down syndrome (DS) using only ultrasound-based protocols. To investigate whether maternal age (MA) has an impact on the efficacy of the ultrasound-based screening methods. Methods: In a prospective study, 6,265 patients were examined. Two ultrasound-based risk calculation protocols were applied: ‘NT' (based on nuchal translucency) and ‘NT+' (based on NT and secondary markers). Results: A total of 5,696 patients were enrolled for analysis; 84 subjects with T21 were identified. Combinations of abnormal ultrasound markers were observed in only 1.2% of euploid fetuses compared to 71.5% of fetuses with T21. Among 17.9% of DS cases with cardiac anomaly, 14.3% comprised atrioventricular septal defects. For a false-positive rate of 3%, the detection rates of T21 were 73.8 and 91.7% for the ‘NT' and ‘NT+' protocols, respectively. The efficacy of both methods was affected by MA. Conclusions: Most of the fetuses with DS demonstrate a combination of ultrasound markers of aneuploidy in the first trimester. The ‘NT+' protocol is efficient and provides comparable performance as a combined screening test. It is a valuable method, especially when the access to biochemical analysis is restricted.

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound Only?

Wiechec¹,

Knafel²,

Nocun³

et al. 2015

“…Regarding the expanded combined test, an improved screening efficacy has been reported in previous studies, obtaining both an increased DR and a reduced FPR (10-29%) [15,25]. In our series, only the addition of DV or NB ± DV to the combined test resulted in a reduction of FPR by about one fourth (25-29%), similar to that reported in a previous study [14].…”

Section: Discussionsupporting

confidence: 80%

“…They can be concurrently assessed in all pregnancies (expanded combined test), or sequentially in selected pregnancies, with either lower (stepwise sequential screening) or intermediate risk (contingent screening) [11,12,13]. Typically these additional markers may decrease the false positive rate resulting from the combined test [14,15]. …”

Section: Introductionmentioning

confidence: 99%

Likelihood Ratios to Apply for Nasal Bone, Ductus Venosus and Tricuspid Flow at the 11-13 Weeks' Scan in Down Syndrome Screening

Illa¹,

Mula²,

Arigita³

et al. 2013

Objective: To assess the feasibility of nasal bone (NB), ductus venosus (DV) and tricuspid flow (TF) at the 11-13 weeks' scan, calculate likelihood ratios for each of the markers and evaluate their efficacy in expanded and contingent screening strategies for Down syndrome. Material and Methods: NB, DV and TF were assessed in 11,261 singleton fetuses undergoing first trimester combined screening. For each marker, Down syndrome detection rate (DR), false positive rate (FPR), positive, negative and isolated likelihood ratios (PLR, NLR and iLR) were calculated. Likelihood ratios were multiplied to the combined test risk either to the entire population or to the intermediate risk group (expanded and sequential strategies, respectively). Results: Down syndrome was diagnosed in 101 pregnancies. Feasibility for marker assessment ranged from 71 to 97%, DRs for isolated markers from 20 to 54% and FPRs from 1.3 to 5.3%. PLR ranged from 10 to 15, NLR from 0.5 to 0.8 and iLR from 3.9 to 5.6. When ultrasound markers were added to both strategies, a significant FPR reduction was observed. Conclusion: The application of NB, DV and TF likelihood ratios to the combined test risk, either in an expanded or contingent strategy, result in a FPR reduction.

“…Although the assessment of TR in the first trimester is achievable in approximately 98% of cases [26] , it is unlikely that it will be routinely used to screen for CHD in a first-level low-risk screening setting. It is more likely to be used in tertiary fetal medicine units.…”

Section: Clinical and Research Implicationsmentioning

confidence: 99%

Fetal Tricuspid Regurgitation in the First Trimester as a Screening Marker for Congenital Heart Defects: Systematic Review and Meta-Analysis

Scala¹,

Morlando²,

Familiari³

et al. 2017

Background: Assessment of tricuspid flow has been reported to improve the performance of screening for aneuploidies and congenital heart defects (CHD). However, the performance of tricuspid regurgitation (TR) as a screening marker for CHD in euploid fetuses is yet to be established. The main aim of this meta-analysis was to establish the predictive accuracy of TR for CHD. Methods: MEDLINE, Embase, and the Cochrane Library were searched electronically utilizing combinations of the relevant medical subject heading for “fetus,” “tricuspid regurgitation,” and “first trimester.” The outcomes explored were prevalence of TR in an euploid population, strength of association between TR and CHD, and predictive accuracy of TR for CHD in euploid fetuses. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio for the overall predictive accuracy of TR for the detection of CHD were computed using the hierarchical summary receiver-operating characteristics model. Results: A total of 452 articles were identified; 60 were assessed with respect to their eligibility for inclusion and a total of 4 studies were included in the study. TR was associated with an increased risk of CHD (RR: 9.6, 95% CI 2.8-33.5; I²: 92.7%). The strength of association between TR and CHD persisted when considering fetuses at risk for CHD, such as those with increased nuchal translucency (RR: 7.2, 95% CI 5.2-9.8; I²: 0%), while TR did not show any association with CHD when detected in a population at low risk for cardiac defects (RR: 9.3, 95% CI 0.8-111.8; I²: 93%). The overall diagnostic performance of TR in detecting CHD was poor in detecting CHD (sROC: 0.684, SE: 0.61) with a sensitivity of 35.2% (95% CI 26.9-44.1) and a specificity of 98.6% (95% CI 98.5-98.7). Detection of TR at the 11-14 weeks' scan showed a positive likelihood ratio of 7.2 (95% CI 5.3-9.8) in detecting CHD when applied to a population at risk for CHD such as fetuses with an increased nuchal translucency. Conclusion: The detection of TR in the first trimester increases the risk of CHD. However, isolated TR in the first trimester does not seem to be a strong predictor for CHD.