The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 299
to explain their significance in a balanced way, to indicate that, in the majority of fetuses, they are an
incidental finding and that they are likely to disappear before birth. Results of a follow-up study (mean:
35.5 ± 16.2 months) on 76 children who as fetuses were found to have CPCs are also reassuring; no
effect on development was found as measured by the Denver II Developmental Screening Test (200).
Periodic cranial ultrasound should be performed after birth until the cysts have resolved.
Short Humerus or Femur
Measurement of the long bones of the fetus does not require the same level of expertise as evaluating
more subtle structural malformations. Thus, because shortness of the long bones is associated
with an increased risk of chromosome abnormalities and because the length is relatively easy to
measure, several investigators have focused on this finding as a way of increasing or decreasing a
woman’s a priori risk of having a fetus with a chromosome abnormality.
Shortness of the humerus and the tibia could have greater sensitivity in detecting trisomy 21 than
shortness of the femur and fibula, as was found in a prospective study of 515 patients between 14 and
23 weeks’ gestation who were at increased risk for a chromosome abnormality because of age or
triple marker screening results or both (201). Tables of risk for trisomy 21 for maternal age and
maternal serum screening positivite status were developed that take into account all four long bones’
lengths being normal versus one, two, three, or four bone lengths being normal. Use of this approach
led to the conclusion that if all long bone lengths are normal, amniocentesis might not be recommended
to women under age 40. Others have not found femur length to be reliable in ultrasound
screening of trisomy 21 (202,203), although humerus length does appear to be associated (203). The
positive predictive value for trisomy 21 in women with risks of 1 in 500 and 1 in 1000 was found to
be 2.3% and 1.2%, respectively.
A significant confounder, however, is that long bone length varies with race, and this factor has
not been taken into account in most studies. In a fetal biometry study of Asians, the long bone lengths
were measured in more than 6000 fetuses, and the conclusion was that the reference charts derived
should be used in all Asian fetuses (204). Thus, use of fetal biometric measures should be cautiously
interpreted with racial factors in mind.
Hyperechoic Bowel
Hyperechoic bowel (HEB), also known as echogenic bowel and hyperechogenic fetal bowel, is a
qualitative ultrasound finding of unclear significance. It has been described as a normal variant with
an incidence of 0.2–0.56%, as reviewed by several authors (205–208). It is also associated with
several adverse outcomes, including fetal chromosome abnormalities, fetal cytomegalovirus infection,
other infections, cystic fibrosis (CF), intrauterine growth restriction, fetal demise, and intestinal
obstruction possibly related to CF (205,206,208–216). The presence of coexisting elevated maternal
serum α-fetoprotein increases the risk of adverse outcome, particularly fetal IUGR and demise
(206,216). See Table 13. The above-referenced studies describe the finding of HEB on secondtrimester
ultrasound examination. Third-trimester HEB associated with trisomy 21 has also been
reported in a fetus in which the second-trimester scan did not show HEB (217).
The incidence of HEB in second-trimester fetuses with trisomy 21 is 7% (218). The relative risk of
adverse outcome in isolated HEB is 6.5 (216).
Part of the reported variation in outcome of HEB is the result of different degrees of brightness of the
finding and also to intermachine and interobserver variability (see Fig. 7). Grades of echogenicity, from
0 (isoechoic) to 3 (bonelike density) have been used (206,215), but even those compare the finding to
different fetal parts—liver versus iliac crest, for example. The more hyperechoic, the higher the risks.
Another reason for variability in reported outcomes relates to the a priori risks. For example, Caucasian
non-Hispanic patients have a much higher a priori risk of CF than individuals of other races.
What causes the finding of HEB? One group (216) commented on the decreased microvillar
enzymes in amniotic fluid in pregnancies affected by trisomy 21, trisomy 18, and CF. It was thought