The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 281
(85,86). Monni et al. (87) suggested that the incidence and severity of limb defects was related to the
gauge of the needle, because they used a 20-gauge needle, whereas Firth used an 18-gauge needle. In
a series of 525 CVS procedures done before 66 days’ gestation, no severe limb defects were seen, and
only 2 mild defects were seen in 2227 procedures that were done later (87). Mahoney (88) then
reported on two multicenter studies that compared transcervical CVS with amniocentesis, and another
comparing TA CVS with transcervical CVS. Of 9588 pregnancies studied, 88% of the CVS
procedures were performed after 66 days’ gestation. Significant limb-reduction defects were present
in seven babies. Two of these defects were longitudinal, and five were transverse. Another baby had
minor reduction defects of the toes. They compared these abnormalities to those reported to the
British Columbia registry and found no significant increase in these birth defects. The timing of the
CVS procedures that resulted in babies with abnormalities ranged from 62 to 77 days’ gestation.
Similar conclusions were reached in a study in which 12,863 consecutive CVS procedures were
performed (89). Five limb reduction defects were seen, which were found not to be significantly
different from the incidence observed in the British Columbia registry of birth defects. Of the 12,863
procedures, 2367 were done at 56–66 days, and 1 of the limb defects was seen in this group. The
authors observed no gestational-time-sensitive interaction related to CVS and postulated that this
was the result of their larger experience base.
In 1993, Jahoda et al. reported on 4300 consecutive transabdominal and transcervical CVS cases for
which newborn follow-up information was obtained (90). Of the 3973 infants born in this group, 3
(0.075%) had a terminal transverse limb defect. Two of these occurred in the transcervical CVS group
sampled before 11 weeks’ gestation (1389 patients), and the other one was in the transabdominal CVS
group, sampled after 11 weeks (2584 patients). The authors found the latter figure to be comparable to
the prevalence figure given in population studies. They concluded that postponement of CVS to the late
first or early second trimester of pregnancy would contribute to the safety of the procedure.
In the same year, a report of the National Institute of Child Health and Human Development
Workshop on Chorionic Villus Sampling and Limb and Other Defects was issued (91). The conclusions,
based on a review of the literature, were mixed; some concluded that exposure to CVS appeared
to cause limb defects, whereas others did not. All agreed that the frequency of oromandibular-limb
hypogenesis appeared to be more common among CVS-exposed infants. This seemed to correlate
with CVS performed earlier than 7 weeks postfertilization (9 weeks after last menstrual period).
Whether or not a distinctive type of limb defect was associated with CVS could not be determined,
and it also was unclear whether the CVS-exposed infant had an increased frequency of other malformations,
including cavernous hemangiomas.
A five-center retrospective cohort study was performed by the Gruppo Italiano Diagnosi Embrio–
Fetali to examine this issue, with results published in 1993 (92). Of 3430 pregnancies in which CVS
had been performed, outcome information was available for 2759. Of these, 3 had transverse limb
reduction defects, 2 among 804 CVS procedures performed at 9 weeks, and 1 among 1204 CVS
procedures performed at 10 weeks. There were no limb reduction defects noted in 2192 amniocenteses
with completed follow-up performed during the same study period. The authors concluded that
performing CVS at less than 10 weeks’ gestation “should be discouraged until further evidence against
this association can be obtained” while noting that their follow-up rate was only 80%.
Hsieh et al. (93) surveyed 165 obstetric units in Taiwan regarding the incidence of limb defects
with and without CVS. Of these, 67 hospitals responded, representing 78,742 deliveries. The incidence
of limb defects was found to be 0.032% in the general population and 0.294% in the CVS
population. The abnormalities seen in the CVS group included amelia, transverse reductions, adactylia,
and digit hypoplasia, much like the abnormalities reported by Firth et al. (84). The 25 limb
abnormalities in the non-CVS group involved syndactyly or polydactyly. In addition, oromandibularlimb
hypogenesis was seen in 4 of 29 CVS cases with limb abnormalities but in none of the non-CVS
cases with limb abnormalities. The severity of the post-CVS limb abnormalities appeared to correlate
with timing of the procedure, and the authors recommended performing CVS only after 10 full gestational
weeks to minimize the risks.