Ultrasonographic “soft markers” of fetal chromosomal defects

Detecting them may do more harm than good

Most women in Britain have at least one ultrasound scan during their pregnancy. Aside from confirming viability and establishing gestational age, ultrasound may also indicate the possibility of an abnormality. An obvious structural problem, such as anencephaly, will have predictable consequences that can be discussed with the patient with some confidence. Less straightforward is the case in which a scan identifies a so called “soft marker”–a minor, usually transient, structural change which may indicate a risk of serious fetal anomaly but which in itself is probably inconsequential.

Ultrasound imaging has improved vastly in quality, and for this reason, and because first trimester scans are now performed more often, the frequency with which “markers” are observed has risen correspondingly. Some markers may well have disappeared by the time of the “routine” scan at 18-20 weeks.

Of those markers indicating pathology, most are associated with an abnormal karyotype. The presence of two or more markers makes this much more likely, although some markers, such as nuchal translucency, have a significant association with chromosomal anomalies even when they occur alone.

Measurement of nuchal translucency has now been refined to the point where risk can be calculated with some precision.1 When the test is performed between 10 and 14 weeks, one study suggests that about 6% of low risk and 16% of high risk women will be positive and merit further investigation by invasive prenatal diagnosis.2 The sensitivity for aneuploidy is about 85%.2 However, about half of those with a chromosomal disorder are likely to undergo spontaneous abortion,3 which throws uncertainty over the precise value of the test. It may be less appropriate for widespread clinical use than was first anticipated, and certainly, other groups have found nuchal translucency screening to be less effective.4

Choroid plexus cysts have also caused controversy. Found in about 1% of fetuses examined before 20 weeks, these structures may, when found in isolation, indicate an overall risk of trisomy of about 1 in 150.5 But their most common association is with trisomy 18, which is almost universally fatal. The residual risk of Down's syndrome is therefore about 1 in 880, so the need for confirmation by invasive prenatal testing cannot be an automatic assumption; maternal age, together with the presence of other risk factors, must be taken into account.

Another marker, minor dilatation of the fetal renal pelvis (pyelectasia), has a background incidence of about 1% and was originally thought to be fairly strongly associated with Down's syndrome.6 Although this association holds when pyelectasia is found with other markers,7 the risk in isolation may be small. However, identification of this marker may confer other long term advantages, since its presence may indicate a baby at subsequent risk of urinary tract abnormalities.8

Ultrasonically echoreflective bowel (bright gut), short femurs, clinodactyly of the fifth digit, and oddly shaped heads have all been identified as soft markers associated with an increased risk of trisomy. The risk associated with any one of these may be little greater than that conferred by maternal age, but if other markers are also present the likelihood of a karyotypic problem rises dramatically.

The problem with soft markers is that, even when karyotypic abnormalities are excluded, the mother and her obstetrician will remain in doubt as to their significance–a cause of considerable anxiety.

Information about ultrasonographic markers is relatively new. Many of the background data come from referral units and are therefore biased. These markers promise to be useful in screening for chromosomal abnormalities when considered alongside maternal age. But such screening may not be feasible when searching for soft markers requires more time and probably better equipment and training than a standard scan; and it may not be ethically acceptable when identifying these markers increases anxiety, usually unnecessarily and often without prior counselling.

The role of ultrasonographic soft markers and their relation to serum screening is therefore unclear. If markers are to form part of the routine ultrasound examination three criteria must be fulfilled: the complexity of diagnosis must be matched by technical skills and equipment; the counselling offered must be detailed and of high quality; and the costs must be justified by the benefits to women.