The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 275
women with a high maternal serum α-fetoprotein were considered, it was found that they had a
relative risk of spontaneous abortion after amniocentesis of 8.3 compared to women with a normal
maternal serum α-fetoprotein level. This equated to an overall relative risk of 2.3. Other factors
found to increase the risk of spontaneous abortion were transplacental passage of the needle (relative
risk of 2.6) and discolored amniotic fluid (relative risk of 9.9).
An important and often overlooked component of providing risk assessments to patients is the
underlying incidence and timing of pregnancy losses. A prospective study of 220 ultrasonographically
normal pregnancies in women recruited prior to conception (in order to avoid bias of selection) found
a pregnancy loss rate after 8 weeks of 3.2% (54). Other studies have shown a maternal age factor in
the loss rate (38). The prevalence of trisomies is about 50% higher at 16 weeks compared to term
pregnancies (38), so selection against chromosomally abnormal abortuses is still occurring at 16
weeks. The incidence of spontaneous pregnancy loss after 16 weeks is 1%.
Some genetic counselors and amniocentesis practitioners counsel patients regarding the risk of the
amniocentesis relative to the risk of a fetal chromosome abnormality and, in effect, use this as a
decision point. In this way, a woman with a risk of fetal chromosome abnormality of 1 in 200 might
be inclined to decline amniocentesis if the risk of miscarriage as a result of the procedure was quoted
as 1 in 100 and the risks compared during the counseling session. A maternal age of 35 has traditionally
been used as a cutoff for the definition of advanced maternal age, because the risk of a fetal
chromosome abnormality at this age is roughly equivalent to the originally reported risk of miscarriage
as a result of the amniocentesis. This is not sound reasoning because the burdens of the risks are
quite different—one burden being the potential lifetime task of caring for an individual with mental
retardation and physical/health problems and the other being miscarriage of a potentially healthy
fetus (55).
Early Amniocentesis
Interest in early amniocentesis (EA) has risen in recent years, as a result in large part the continued
desire to provide and receive prenatal diagnosis at an earlier gestation without some of the risks and
limitations associated with CVS, which are outlined in the following paragraphs. An increase in
sophistication in ultrasound technology has also made earlier imaging of fetuses more feasible and
has added to the confidence level of the physicians performing the procedure. Adding to this is the
opportunity to measure amniotic fluid α-fetoprotein and acetylcholinesterase, which is not possible
with CVS. One center reported a rise in EA procedures from 3.2% of their 495 procedures in early
1985 to 6.5% of 980 procedures in late 1987 (56).
Early amniocentesis is usually described as one that occurs before 15 weeks’ gestation. It has been
shown that the earlier a prenatal diagnosis procedure is performed, the higher the fetal loss rate is
(57). One should, therefore, further divide the periods at which amniocentesis is performed to provide
better comparative data for a variety of procedures since “true risks . . . appear to be a function
of gestational age and less related to the procedure performed” (57).
Although the procedure by which EA is performed is similar to that of mid-trimester amniocentesis,
practitioners report several challenges unique to EA. The placenta is more widely spread, the
amniotic fluid volume is lower and the amniotic membrane is not yet totally adherent to the uterine
wall, leading to the “tenting” reported by some physicians (58).
BACKGROUND
In one study conducted from 1979 through 1986, 4750 amniocenteses were performed, 541 of
which were performed before the 15th week since the last menstrual period (59). Outcome data were
available for 298 women, of whom 108 were under 35 years of age. Fetal loss within 2 weeks of the
procedure was seen in 5 pregnancies, all in the 14th week, when 228 of the 308 women had the
procedure. When all spontaneous fetal losses were accounted for, there were 11 spontaneous abortions
(3.6%), 2 stillbirths (0.7%), and 1 neonatal death (0.3%), resulting in a total postprocedure loss