The Principles of Clinical Cytogenetics - Extra Materials - Springer

Prenatal Cytogenetics 301
Fig. 7. Ultrasound image of moderately hyperechoic bowel (indicated by +’s and circle of dots) in a 17-wkgestation
fetus. ST = stippling, referring to pattern of hyperechogenicity. (Courtesy of Greggory DeVore, M.D.)
Positive Maternal Serum Marker Screen
High Maternal Serum α-Fetoprotein
The association between an elevated level (2.0 or 2.5 multiples of the median) of maternal serum
α-fetoprotein (AFP) and fetal neural tube defects has been known for many years. More recently, the
presence of an unexplained elevated level of maternal serum AFP has been found to be associated
with an increased risk for fetal chromosome abnormalities, with an incidence of 10.92 per 1000
amniocenteses (224). Of these, fetal sex chromosome abnormalities were seen in 47%. Thus, although
some practitioners discourage patients from having an amniocentesis with an elevated AFP and a
normal ultrasound study, the facts that sex chromosome abnormalities other than 45,X and its related
karyotypes have no significant associated ultrasound abnormalities and that they are quite common
(with incidences of 47,XXX, 47,XXY, and 47,XYY each greater than or equal to 1 in 1000 liveborns)
support consideration of amniocentesis in this group.
Low Maternal Serum AFP and Multiple Marker Screening
The association between low maternal serum AFP and fetal Down syndrome was established in
1984 (225), and in 1987, the association between high maternal serum human chorionic gonadotropin
(hCG) (226) and low unconjugated estriol (227) and fetal Down syndrome was established. These
three substances, or markers, are combined now in what is commonly known as triple marker screening
(TMS). Hundreds of thousands of women in the United States have TMS in the second trimester
of pregnancy, with a resultant increase in detection of trisomy 21 before age 35 and what appears to
be a decrease in the incidence of Down syndrome births because of abortion of affected fetuses. The
overall detection of trisomy 21 with TMS is about 65% with a mid-trimester risk cutoff of one in 190,
with a much lower detection in young women (about 44% in 18-year-olds) and a much higher detection
in older women (about 78% in 36-year-olds) (228).
Triple marker screening detects 60% of trisomy 18 fetuses as well, when a midtrimester risk cutoff
of 1 in 100 is used (229).
Less recognized is the fact that TMS detects many chromosome abnormalities nonspecifically, for
unknown reasons. Thus, for every trisomy 21 fetus found by TMS, a fetus with a different chromosome
abnormality is also detected (230). This is important to keep in mind when counseling patients.