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

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.

JAMA. 2001;285:1044-1055