The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 279
and the patients not randomized, and the time intervals were different. Although all procedures were
listed as initial cases, the relative degree of prior individual practitioner experience in the two procedures
was not addressed.
In 1994, Nicolaides et al. (75) reported on a prospective, partially randomized study comparing
EA and TA CVS in 1870 women. The spontaneous loss rate was significantly higher after EA at 5.3%
than with the CVS group (1.2%). The rate of successful sampling was the same at 97.5%. Culture
failure occurred in 2.3% of the EA group, compared to 0.5% in the CVS group. Confined or true
mosaicism was seen in 1.2% of the CVS group, compared to 0.1% of the EA group. The authors
concluded that although EA and CVS are equally likely to produce valid cytogenetic results, CVS
would probably become the “established technique” as a result of the 2–3% excess risk of fetal loss in
the EA group.
In response to this study, Saura et al. (76) stated that EA could be a “true alternative” to CVS after
the 13th week, when the disadvantages of culture failure and fetal losses decrease. Bombard et al.
(77) reported 1 loss in 121 procedures (0.83%) performed by 1 practitioner at 10–13 weeks using a
22-gauge needle. They suggested that Nicolaides’ higher EA fetal loss rate could be related to the
needle gauge and the multiple practitioners in his study, compared to one practitioner in Bombard’s
center.
Similar results were reported by Vandenbussche et al., who, in a partially randomized study,
reported 8 fetal losses among 120 EA procedures, compared to none among the 64 CVS patients with
a follow-up of 6 or more weeks (78).
Another response to these reports proposed the idea that the main drawback to the studies was the
very small numbers of EA procedures performed and the evident greater practitioner experience with
CVS than with EA. The authors reported a spontaneous abortion rate after EA of 1% up to week 24
on the basis of 1800 pregnancies. The culture failure rate was 0.3% for gestations ranging to 10 weeks
4 days (79).
An important consideration raised by some investigators (73,79) is that the banding quality of
amniocentesis specimens of any gestation is generally superior to that of CVS specimens, which
increases the informativeness of the cytogenetic analysis. The fact that amniotic fluid α-fetoprotein
levels and multiples of the median have been established in many laboratories down to 12 or 13
completed weeks of gestation adds another advantage to the diagnostic power of EA compared to
CVS (80).
A 14-center study of 3775 women randomized to having either CVS or EA was conducted to try to
provide more answers to the questions as to the safety and accuracy of EA and transabdominal CVS
at 11 to 14 weeks’ gestation. Both types of procedure were performed by the physicians in each
center. Early in the trial, reports of clubfoot at 11–12 weeks in EA patients caused procedures at these
weeks to be discontinued.
Criteria for inclusion included advanced maternal age, serum marker screen positive, and prior
trisomy. The primary outcome was deemed to be preterm delivery or pregnancy loss of a cytogenetically
normal fetus at less than 28 weeks’ gestation. Secondary outcomes included total fetal loss,
including neonatal death, amniotic fluid loss, pregnancy outcome, limb and other congenital defects,
and cytogenetic diagnostic success and accuracy. Multiple procedures were required for EA at 11–12
weeks (2.4% vs 1.2% for CVS). Maternal cell contamination was seen in EA specimens at 11- to
12- and 13-week gestation (0.6% in both cases vs 0% in CVS). Pseudomosaicism was seen in 1.2%
of EA 11- to 12-week specimens versus 0.6% of CVS specimens. CVS specimens were harvested at
5.9–6.5 days across the sampling period, compared to 12.3–9.8 days for 11- to 12- or 14-week EA
specimens, respectively. As for complications, the only difference that reached significance at the
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