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Second-Trimester Ultrasound to Detect Fetuses With Down Syndrome A Meta-analysis

Rebecca Smith-Bindman, MD; Wylie Hosmer, BS; Vickie A. Feldstein, MD; Jonathan J. Deeks, MSc; James D. Goldberg, MD
JAMA. 2001;285(8):1044-1055. doi:10.1001/jama.285.8.1044.
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Context Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown.

Objective To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses.

Data Sources English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches.

Study Selection Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included.

Data Extraction Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations.

Data Synthesis When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant).

Conclusions A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome.

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Figure 3. Sensitivity for All Studies That Examined Nuchal Fold Thickening
Graphic Jump Location
Data shown for all studies using nuchal fold thickening as a screening test for Down syndrome. Studies are stratified by whether the nuchal fold was evaluated as an isolated abnormality, was seen in conjunction with other abnormalities, or the study did not report whether the nuchal fold was seen as an isolated abnormality (unknown). For studies in which data could be abstracted for both an isolated nuchal fold and for a nuchal fold seen in addition to other abnormalities, 2 data points are included. Size of data markers reflects study sample size; dotted line reflects the point estimates for pooled data.
Figure 2. Sensitivity and False-Positive Rates (1 − Specificity)
Graphic Jump Location
Data shown for all studies that examined the ultrasonographic markers as screening tests for Down syndrome. One summary estimate is included for each study. The category of "composite findings" was defined differently by each study, but in general included some or all of the markers, in addition to structural abnormalities. Error bars indicate 95% confidence intervals.
Figure 1. Fetal Ultrasonographic Markers for Risk of Down Syndrome
Graphic Jump Location
A, Fetal brain with a choroid plexus cyst. B, Fetal neck demonstrating thickening of the nuchal region. C, Bright focus in the fetal heart (echogenic intracardiac focus). D, Dilation of the renal collecting systems (renal pyelectasis). E, Increased brightness in the fetal bowel (echogenic bowel). Humeral and femoral shortening are defined by comparing measurements to a normal distribution and are not illustrated.



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