An 8‐Center Study to Evaluate the Utility of Midterm Genetic Sonograms Among High‐Risk Pregnancies

Abstract

Objective. A multicenter study was undertaken to evaluate the diagnostic efficacy of a genetic sonogram. Methods. Eight centers provided data on 176 pregnancies complicated by fetal Down syndrome. One hundred thirty-four pregnancies were considered high risk because of advanced maternal age (>35 years), and 42 were considered high risk for having "abnormal" triple-screen results (risk >1:250). Each center provided fetal biometric data, information regarding the presence or absence of major structural abnormalities, and between 3 and 6 additional ultrasonographic markers for trisomy 21. The heterogeneity of our 8 independent "sensitivity estimates" was evaluated by Poisson regression, and a single combined estimate of the sensitivity was calculated. Results. Of the total 176 cases of trisomy 21, 125 fetuses (71.0%) had either an abnormal long bone length (femur length, humerus length, or both), a major structural abnormality, or a Down syndrome marker. The combined diagnostic sensitivity was 71.6%, with a range of 63.6% (7 of 11) to 80% (8 of 10). Five centers had sensitivity estimates falling between 64% and 76%. The sensitivity of individual markers varied between 3% (sandal gap) and 46.5% (nuchal skin fold thickness). A condensed regimen of nuchal skin fold thickness, femur length, and a standard anatomic survey would screen in 56.8% of fetuses with Down syndrome. Conclusions. This 8-center study that included many fetuses with Down syndrome validates the concept that the genetic sonogram can be used to better adjust the Down syndrome risk for high-risk patients.

Second-Trimester Biparietal Diameter/Nasal Bone Length Ratio Is an Independent Predictor of Trisomy 21

“…A number of sonographic abnormalities or "soft markers" have been associated with trisomy 21; some authors have combined these results to provide a risk score or probability for trisomy 21. 3,4 The goal of such prenatal screening programs is accurate detection of fetal aneuploidy and avoidance of unnecessary invasive diagnostic testing. For this purpose, ultrasound has proved to be an invaluable diagnostic and screening tool.…”

Trends in Serial Measurements of Ultrasound Markers in Second and Third Trimester Down Syndrome Fetuses

“…Unfortunately, large studies investigating the reproducibility of NF measurements in both normal and DS fetuses are lacking [8,24,25]. We speculate that the reason for the great variation in NF and the apparent lack of trend in the measurement with gestation is probably the consequence of the difficulty in standardizing the scanning plane where the measurement is taken.…”

Screening for aneuploidy in first and second trimesters: is there an optimal paradigm?

“…In spite of an expanded panel of potential markers under consideration (iliac angle [33,34], ear length [35], clinodactyly [36], sandal-gap toe [37,38], absent or short nasal bone [39,40]), in clinical practice the principal markers that comprise the genetic sonogram have remained unchanged in recent years and include the nuchal fold, short femur or humerus, pyelectasis, echogenic bowel, echogenic intracardiac focus and any major structural malformation. Identification of any of these markers, in isolation or in combination, leads to adjustment of the a priori risk for trisomy 21 (based on either maternal age or preferably prior screening results) using likelihood ratios calculated for each marker.…”