The Principles of Clinical Cytogenetics - Extra Materials - Springer

288 Linda Marie Randolph
The underlying fetal pathology is a significant factor in fetal loss rate. Of these 12 losses, 10 were
fetuses with a chromosome abnormality or severe fetal growth restriction. In gestations from 17 to 38
weeks, Maxwell et al. (132) compared the loss rates within 2 weeks of the procedure with the indications.
Of 94 patients having prenatal diagnosis with normal ultrasound findings, 1 pregnancy of the
76 that were not electively terminated was lost. Of the group with structural fetal abnormalities, 5 in
76 were lost, and in the group of 35 with nonimmune hydrops, 9 were lost. It is important to take this
factor into account when counseling patients before the procedure.
It has been said that no other fetal tissue “can yield such a broad spectrum of diagnostic information
(cytogenetic, biochemical, hematological) as fetal blood” (129). As a means of fetal karyotyping,
it has the advantage of generating results in 2–4 days, compared to 6–14 days or more for amniotic
fluid and CVS cells. When pseudomosaicism or mosaicism is seen in amniotic cell cultures, PUBS
can provide valuable additional information regarding the likelihood of true mosaicism (133–136)
and thereby assist the couple in their decision-making.
Although pseudomosaicism in amniotic fluid cell cultures is usually associated with normal chromosome
analysis after PUBS, the absence of trisomic cells in fetal blood does not guarantee that
mosaicism has been definitely excluded (137). For example, fetal blood karyotyping is not useful for
the evaluation of mosaic or pseudomosaic trisomy 20. For further discussion of mosaicism, see the
section Special Issues below and Chapter 8.
Because PUBS is associated with a significantly higher fetal loss rate than other prenatal diagnostic
procedures, use of this technique should be recommended and provided with great care and only
in certain high-risk situations such as those mentioned previously.
Specimen Requirements
Ideally, 1–2 mL of blood should be obtained and put into a small sterile tube containing sodium
heparin. Results can usually be obtained from 0.5 mL, and in some cases, 0.2 mL, so even small
amounts obtained should not be discarded. A Kleihauer–Betke test might be useful in evaluating the
possibility of maternal cell admixture, particularly when a 46,XX karyotype results.
INDICATIONS FOR PRENATAL CYTOGENETIC DIAGNOSIS
Advanced Maternal Age
Advanced maternal age, generally defined in the United States as 35 or older at delivery, is the most
common indication for prenatal cytogenetic diagnosis. For women in this age group, this indication
alone provides the advantage of greater than 99% accuracy for detection of chromosome abnormalities.
The chief disadvantage lies in the fact that, overall, it results in the detection of only 20% of chromosomally
abnormal fetuses, given that 80% of chromosomally abnormal babies are born to women under
age 35. Advanced maternal age is the most significant determinant of the risk of a chromosome abnormality
for all trisomies, structural rearrangements, marker chromosomes, and 47,XXY (Klinefelter syndrome;
see Chapter 10). Maternal age is not a factor in 45,X (Turner syndrome), triploid (69
chromosomes instead of 46), tetraploid (92 chromosomes instead of 46), or 47,XYY karyotypes.
Very young women are also at increased risk of fetal chromosome abnormality. A 15-year-old has
a 1 in 454 risk of having a term infant with a chromosome abnormality, compared to a 1 in 525 risk
for a 20-year-old and a 1 in 475 risk for a 25-year-old (138) (see Fig. 2).
Women 31 and Older with Twin Pregnancies
A 31-year-old woman with a twin gestation of unknown zygosity has a risk comparable to that of
a 35-year-old woman; this is calculated as follows: Given that two-thirds of such twins are dizygotic,
the risk that one or the other has a chromosome abnormality is about 5/3 times that of a singleton
pregnancy for that age. Thus, given that a 31-year-old woman’s risk is 1 in 384 at term for any
chromosome abnormality, if she is carrying twins of unknown zygosity, the risk that one or the other