Sonographic Markers Related to Risk for Trisomy 21

The presence of multiple markers in a second-trimester sonographic scan is associated with a much higher risk for trisomy 21, according to the findings of a meta-analysis.

M. Agathokleous, from the Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, United Kingdom, and colleagues published their findings online January 24 in Ultrasound in Obstetrics & Gynecology.

The researchers mention that previous studies identified a number of second-trimester sonographic findings that may be associated with an increased risk for trisomy 21. "The most widely examined markers are lateral cerebral ventriculomegaly, absent or hypoplastic nasal bone, increased nuchal fold thickness, intracardiac hyperechogenic focus, aberrant right subclavian artery...hyperechogenic bowel, mild hydronephrosis and shortening of the femur or humerus," the authors write. "Assessment of the risk for trisomy 21 based on each of these markers necessitates knowledge of their prevalence in trisomic and euploid fetuses."

In the study, the authors performed a meta-analysis of 48 studies that reported the incidence of 1 or more markers of trisomy 21 in fetuses in the second trimester (14 - 24 weeks) that were assumed to be euploid and that described both euploid and trisomy 21 fetuses, did not know the fetal karyotype at the time of sonographic examination, and confirmed the chromosomal status of fetuses by karyotypic or postnatal clinical examination. The absence of all sonographic markers, including short femur but not short humerus, was associated with a combined likelihood ratio of 0.13 (95% confidence interval, 0.05 - 0.29), indicating that the risk for trisomy 21 was reduced by 7.7-fold.

Conversely, the absence of all markers including short humerus but not short femur was associated with a likelihood ratio of 0.12 (95% confidence interval, 0.06 - 0.29), indicating a reduction in the risk for trisomy 21 by 8.3-fold.

Although most individual markers were not associated with substantial increases in the risk for trisomy 21 after excluding cases with major defects, the presence of ventriculomegaly, increased nuchal fold, aberrant right subclavian artery, and hypoplastic nasal bone alone increased the risk for trisomy 21 by 3.57-, 3.12-, 3.94-, and 6.58-fold, respectively.

"Further studies are needed to establish reference ranges for each biometric marker and to estimate the effect of gestational age on screening performance," the authors note. "In the interim the data arising from this meta-analysis and their interpretation could form the basis for clinical practice. However, as in the case of fetal [nuchal translucency], it is essential that those performing the second-trimester scan receive appropriate training and certification of competence and subject their results to regular audit."

The authors have disclosed no relevant financial relationships.

Ultrasound Obstet Gynecol. Published online January 24, 2013. Abstract