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.

Resultados perinatales y obstétricos en fetos con translucencia nucal incrementada / Perinatal and obstetric outcomes in fetuses with increased nuchal translucency

El objetivo es analizar los resultados perinatales y obstétricos de las gestaciones en cuya ecografía del primer trimestre se objetivó translucencia nucal incrementada. Obtuvimos 170 translucencias nucales aumentadas (mayor o igual a 3,5 mm), en 62 casos (36,47%) el cariotipo fue normal, en 84 casos (49,41%) fue patológico y en 24 casos (14,11%) no se realizó técnica invasiva. Del total de cariotipos normales (62 casos), 47 gestaciones llegaron a término con parto en nuestro centro y recién nacido normal, dos abortos tras realización de técnica invasiva y hubo diez interrupciones legales del embarazo. Los hallazgos ecográficos encontrados son los siguientes: un caso con megavejiga (2,12%), un caso con onfalocele (2,12%), dos casos de higroma quístico (4,3%), dos hidrops fetales severos, ambos con canal aurícoventricular completo, dos ausencias del hueso nasal (4,3%) y cuatro comunicaciones interventriculares (8,5%). En cuanto al total de translucencia nucal incrementada, 39 casos se correspondieron con trisomía del par 21 (23%), 18 con de trisomía 18 (10,6%), 10 con trisomía 13 (5,9%), 14 con 45XO (8,2%), 1 con 47XXX, (0,7% ), 1 con trisomía 10 (0,7%) y 1 con translocación balanceada 45 XX (t 8;21) (p11;q11)(0,7%). El incremento del grosor de la translucencia nucal entre las 11 y 13 semanas y seis días constituye una expresión fenotípica común de las aneuploidías y una gama de malformaciones fetales y síndromes genéticos. En los fetoseuploides, la prevalencia de las anormalidades fetales y los resultados perinatales adversos aumenta con el incremento de la translucencia nucal (AU)

The objective was to analyze the perinatal and obstetric outcomes of pregnancies, in which increased NT was detected onfirst-trimesterroutine ultrasoundstudy. A total of 170 cases of increased nuchal translucency (equal to or higher than 3.5mm)were detected. Within these cases, 62 (36,47%) had normal karyotype, 84 (49,41%) had aneuplody and 24 (14,11%) were not subjected to invasive techniques. From the group of patients with augmented nuchal translucency and normal karyotype (62), 47 reached full-term delivery at our hospital and the newborns were normal; 2 ended in miscarriage after undergoing an invasive technique, 10 ended in legal termination of pregnancy and 3 did not give birth at our hospital and their data were not available. Ultrasound findings in these patients included: one case of megacystis (2,12%), one case of omphalocele (2,12%), two cases of cystic hygroma (4,3%), two cases of severe hydrops fetalis both with complete AV canal (4,3%), two cases of absent nasal bone (4,3%) and four cases of interventricular communication (IVC) (8,5%). From the total of cases of increased nuchal translucency, 39 corresponded to trisomy-21 (23%); 18 (10,6%) to trisomy-18; 10 to trisomy-13 (5,9%); 14 to Turner’s syndrome (8,2%), 1 to karyotype 47XXX (0,7%); 1 to trisomy-10 (0,7%) and 1 to balanced translocation 45 XX (t 8;21) (p11;q11) (0,7%). Nuchal translucency thickening between weeks 11 and 13+6 days is a common phenotypical manifestation of a neuploidy and a wide range of fetal malformations and genetic syndromes. In euploid fetuses, the prevalence of fetal abnormal findings and adverse perinatal outcome increases with the nuchal translucency value (AU)

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.

Análisis de los resultados del programa de cribado prenatal de cromosomopatías en el Área Hospitalaria de Valme (Sevilla). Identificación de áreas para la mejora de la calidad / Analysis of the results of the programme of prenatal screening for chromosomal abnormalities in the Hospital Area of Valme (Sevilla). Identification of measures for the improvement of the quality

Introducción. En los programas de cribado prenatal de aneuploidías el análisis crítico de los resultados del control de calidad, entendido de forma amplia, podría ser una herramienta útil para mejorar la eficacia, sin necesidad de aumentar la complejidad o los costes en dichos programas. En el presente trabajo analizamos nuestros resultados en el periodo 2005-2011 para trisomía 21. Material y método. Se valoraron retrospectivamente los siguientes parámetros: cobertura, solicitudes no conformes, imprecisión y sesgo en la medición de BHCG libre y PAPP-A, evolución de las medianas de múltiplos de mediana de BHCG libre, PAPP-A y translucencia nucal, tasa de detección, tasa de falsos positivos y análisis de falsos negativos para trisomía 21. Los parámetros bioquímicos se determinaron mediante quimioluminiscencia. La estimación del riesgo se realizó mediante el software PRISCA V4.0. Resultados. Se realizaron 26.363 cribados. Cobertura 95,11%. No conformidades entre 12,2% (2005) y 5,8% (2010). Imprecisión inferior al 5% y sesgo inferior al 20% tanto para PAPP-A como para BHCG libre. Mediana de múltiplos de mediana corregidos de 1,066 (PAPP-A), 1,027 (BHCG libre) y 0,829 (translucencia nucal). Sensibilidad del 80% para cribado combinado de primer trimestre (4,6% falsos positivos) con 13 falsos negativos sobre 66 diagnósticos genéticos de trisomía 21. Para trisomía 18, sensibilidad del 77% (4,3% falsos positivos). Conclusión. Áreas de mejoras detectadas: universalización del programa, gestión de solicitudes no conformes, control de calidad ecográfico, diseño del software de cálculo y valoración conjunta de los resultados finales en colaboración entre Unidades de Laboratorio y Obstetricia(AU)

Introduction. Critical analysis of the results of quality control could be a useful tool to improve efficacy without increasing complexity or costs in such programs. We analyzed the results of the prenatal screening program in Valme Hospital in order to, detect and introduce improvement areas. Material and methods. We have studied the non-conformities of the application received, the precision and bias in the measurement of B-HCG and PAPP-A, the medians of PAPP-A, BHCG and nuchal translucency multiples of the medians, the sensibility and false positives rate. We have studied the false negatives results. The biochemical parameters were determined by a chemiluminiscence inmunoassay. Risks estimation was performed using PRISCA V4.0 software. Results. A total of 26,363 prenatal screening were performed. The program reached a coverage of 95,11%. Non-conformities fell from the 12.2 to 5.8%. Imprecision was less than 5% and bias less than 20% for biochemical markers. The corrected medians for PAPP-A, BHCG and nuchal translucency multiples of the medians were 1.066, 1.027 and 0,829, respectively. The sensibility for the first trimester combined screening was 80% (4,6% false positive) for Down's syndrome for a total 66 chromosomal abnormalities diagnosed. We recorded a total of 13 false negatives for trisomy 21. For trysomy 18 detection rate was 77% (4.3% false positive). Conclusion. Areas for improvement identified were: universalization of the program, non-conformities of the received application management, ultrasound quality control, design of risk calculation software and joint evaluation of the final results in collaboration between laboratory and obstetrics units(AU)

Control de calidad de la translucencia nucal. Experiencia en 6 centros del ámbito de primaria / Quality control in nuchal translucency measurement. Experience in six primary care centers

Objetivo. Aplicar el control de calidad de la medición de la translucencia nucal en las ecografías realizadas en primaria en las regiones Vallès y Centre de Catalunya. Sujetos y métodos. Se han evaluado 7.386 ecografías de primer trimestre realizadas durante el año 2009 en el ámbito de primaria en las regiones Vallès y Centre del Institut Català de la Salud (ICS). Se han aplicado 2 métodos de control de calidad de la translucencia nucal: el propuesto por la Fetal Medicine Foundation (FMF) y el propuesto por el grupo de Women and Infant's Hospital Rhode Island (WIHRI). Resultados. El método de la FMI muestra una tendencia global a la infraestimación. Los resultados individuales muestran una infraestimación del 68, el 89 y el 32%, según los porcentajes de mediciones de TN situados en los percentiles p50, p95 y p5, respectivamente. Aplicando el método de WIHRI en la serie general, todos los parámetros están dentro de la normalidad. Al analizar los resultados individuales de la mediana de los MoM se observa que un 43% de los ecografistas presenta una infraestimación. Conclusiones. El control de calidad es poco útil cuando se aplica a toda la serie. En cambio, su aplicación a nivel del ecografista individual permite la detección de los ecografistas que se desvían de forma importante de los valores correctos, y proponer su corrección (AU)

Objective. To apply quality control to nuchal translucency (NT) measurements in the scans performed in two primary care health regions (Vallès and Centre de Catalunya) in Catalonia, Spain. Subjects and methods. We evaluated 7,386 TN measured in 2009 in the prenatal care centers of two health areas (Vallès and Centre de Catalunya) of the Catalan health service. We applied two methods of quality control: the method proposed by the Fetal Medicine Foundation (FMF) and that proposed by the Women and Infants’ Hospital, Rhode Island (WIHRI) group. Results. The FMF method showed that 68% of sonographists underestimated NT when the 50th percentile was assessed. For the 95th and 5th percentiles, the underestimation rates were 89% and 32%, respectively. When the WIHRI method was applied to the overall series, all parameters were within the normal range. Results by individual sonographists showed that 43% underestimated the median value of the multiple of the median (MoM) measurements. Conclusions. NT quality control was not useful when applied to the entire series. Instead, its application in individual sonographists allows those that significantly deviate from the expected values to be identified and corrections to be proposed (AU)

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.