Abnormal nuchal translucency followed by normal microarray analysis is associated with placental pathology-related complications.

OBJECTIVE: Identify placental pathology-related complications, labor and neonatal outcomes in pregnancies complicated by pathological nuchal translucency (NT) with normal microarray analysis. METHODS: A retrospective study in which all women with singleton pregnancy who demonstrated NT above 3 mm and a normal microarray analysis were matched to women with normal NT and a normal microarray analysis (2013-2019) in a single tertiary academic center. The following placental pathology-related parameters were measured: preeclampsia, oligohydramnios, suspected intrauterine growth restriction, abnormal Doppler studies or small for gestational age (SGA) neonates. The primary outcome was defined as a composite of complications related to placental pathology including preeclampsia and SGA neonate. Secondary outcomes were labor complications and neonatal morbidity. RESULTS: A total of 185 women were included in the study: of them, 47 presented an abnormal NT (study group) and 138 presented normal NT (controls). Groups did not significantly differ in baseline characteristics. Regarding primary outcome, all placental-related complications frequencies were higher in the study group, with a composite rate of 17.02% versus 6.52% in controls (p = 0.042%). Secondary outcomes did not differ between groups. CONCLUSIONS: Abnormal NT measurement presented in pregnancies with normal fetal microarray analysis is associated with higher rates of placental-related complications.

Accuracy of nuchal translucency measurement depends on equipment used and its calibration.

OBJECTIVES: To determine the effect of different ultrasound machine-probe combinations on nuchal translucency (NT) measurements and to assess how this impacts on the accuracy of the NT-derived component of first-trimester screening for trisomy 21. METHODS: Sixteen different ultrasound machine-probe combinations were used for axial measurement of 2.0-, 3.0- and 4.0-mm spaced targets in an ultrasound phantom. Differences between the measured and known values were determined. The mean of the axial measurements was used to calculate adjusted risks for trisomy 21, given specific clinical scenarios. RESULTS: Differences observed using different machine-probe combinations for the 2.0-mm target ranged from 1.8-2.2 mm; for the 3.0-mm target, 2.7-3.2 mm; and for the 4-mm target, 3.7-4.3 mm, and exceeded those due to intraobserver variability. For a fetal crown-rump length of 50.0 mm and NT measurement of 2.0 mm, the maximum/minimum measurements in the fetus of a 40-year-old woman led to derived risks ranging from 1 in 32 (NT, 2.2 mm) to 1 in 189 (NT, 1.8 mm) and in the fetus of a 20-year-old with an NT of 3.0 mm these ranged from 1 in 102 (NT, 3.2 mm) to 1 in 160 (NT, 2.7 mm). CONCLUSIONS: We have described the effect of machine-probe combinations on small but very precise ultrasound measurements. Such machine-probe combinations led to greater variability than those ascribed to intraobserver differences, and significantly affected the screening risk for the same fixed measurement. This finding has implications for Down syndrome screening algorithms and audit of ultrasound operators. Furthermore, most ultrasound machines are neither calibrated nor specified for measurements of tenths of a mm.

The influence of image setting on intracranial translucency measurement by manual and semi-automated system.

OBJECTIVE: To investigate the agreement between manual and semi-automated system and the effect of different image settings on intracranial translucency (IT) measurement. METHODS: A prospective study was conducted on 55 women carrying singleton pregnancy who attended first trimester Down syndrome screening. IT was measured both manually and by semi-automated system at the same default image setting. The IT measurements were then repeated with the post-processing changes in the image setting one at a time. The difference in IT measurements between the altered and the original images were assessed. RESULTS: Intracranial translucency was successfully measured on 55 images both manually and by semi-automated method. There was strong agreement in IT measurements between the two methods with a mean difference (manual minus semi-automated) of 0.011 mm (95% confidence interval--0.052 mm-0.094 mm). There were statistically significant variations in both manual and semi-automated IT measurement after changing the Gain and the Contrast. The greatest changes occurred when the Contrast was reduced to 1 (IT reduced by 0.591 mm in semi-automated; 0.565 mm in manual), followed by when the Gain was increased to 15 (IT reduced by 0.424 mm in semi-automated; 0.524 mm in manual). CONCLUSIONS: The image settings may affect IT identification and measurement. Increased Gain and reduced Contrast are the most influential factors and may cause under-measurement of IT.

Semi-automated adjusted measurement of nuchal translucency: feasibility and reproducibility.

OBJECTIVE: The variability of nuchal translucency thickness (NT) measurements in the first trimester appears to be associated in part with caliper placement. Methods for obtaining semi-automated adjusted measurements (SAAMs) can provide several NT values (maximum, minimum, mean and median) automatically within a manually set frame in the zone of interest. This study sought to assess the feasibility and reproducibility of these SAAM-NTs. METHODS: Three readers, two experts and one less experienced, examined archive images of 160 patients and obtained SAAM-NTs from them, on two separate occasions. The intra- and interobserver reproducibility were assessed by calculating the intraclass correlation coefficients (ICCs) for maximum, mean and median SAAM-NTs, and Bland-Altman plots were constructed. RESULTS: SAAM-NTs were technically feasible for all 160 images. The range of ICCs for intraobserver reproducibility was 0.76-0.93 for mean SAAM-NT, 0.76-0.95 for median SAAM-NT and 0.74-0.95 for maximum SAAM-NT. Interobserver ICCs were 0.85, 0.85 and 0.84 for mean SAAM-NT, median SAAM-NT and maximum SAAM-NT, respectively. There were no significant differences for intra- and interobserver reproducibility of median, mean and maximum SAAM-NTs. CONCLUSIONS: SAAM-NT is feasible with a high level of intra- and interobserver reproducibility. This easy-to-use method has the potential to simplify screening during the first trimester. It should be evaluated further and compared with the manual measurement method.

Practical strategies in contingent sequential screening for Down syndrome.

OBJECTIVE: To design and assess the performance of protocols for contingent sequential Down syndrome screening that can be implemented in practice. METHODS: Protocols were designed in which all women received first-trimester measurement of nuchal translucency (NT) together with maternal serum pregnancy-associated plasma protein-A (PAPP-A) and either free beta- or total human chorionic gonadotrophin (hCG). Those women with borderline Down syndrome risks received follow-up second-trimester maternal serum involving double, triple, or quadruple serum screening markers: alpha-fetoprotein, free beta-hCG or total hCG, unconjugated estriol and inhibin-A. Specific ranges of risks were used to define the borderline group. Separate protocols were developed for the United Kingdom and the United States to reflect differences in commonly used tests, cut-offs, and the gestational age at testing. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling with Monte Carlo simulation. RESULTS: Proposed protocols based on first-trimester NT, PAPP-A and free beta-hCG or total hCG, followed by selective use of second-trimester quadruple markers can result in a 91% detection rate and 2.1% false-positive rate for the United Kingdom and a detection rate of 89% and false-positive rate of 3.1% for the United States. For both countries, over 60% of affected pregnancies would be detected in the first trimester and less than 20% of women would require a second-trimester Down syndrome risk assessment. Use of alternative cut-offs to define those with borderline risks or different combinations of second-trimester markers also yielded high detection rates and low false-positive rates. CONCLUSION: With appropriate patient counselling, it should be possible to provide highly effective Down syndrome screening using contingent sequential protocols.