The Principles of Clinical Cytogenetics - Extra Materials - Springer

326 Solveig Pflueger
Table 5
Prenatal Loss of Chromosomally Abnormal Fetuses
Autosomal monosomy 100.0%
Tetraploid 100.0%
Triploid 99.9%
Monosomy X 99.8%
Autosomal trisomy 96.5%
Mosaics 68.8%
Structural rearrangements 53.4%
Sex chromosomal trisomy 11.0%
Source: Adapted from ref. 18.
In the second trimester, ascending infection becomes more frequent as a cause of spontaneous
pregnancy loss. Abnormal karyotypes become less prevalent as pregnancy progresses because many
of the less viable abnormal gestations have already undergone growth arrest and miscarriage. Gaillard
et al. (16) studied 422 consecutive second-trimester losses. Of these, 78.6% were recent demises
without extensive maceration. Ascending infection could explain 85% of these. Structural anomalies
were seen in 7.6% of fetuses. Cytogenetic abnormalities were confirmed or suspected in half of these.
The majority of abnormal fetuses showed maceration consistent with long-standing intrauterine fetal
demise. This, again, confirms the observation that cytogenetic abnormalities are associated with early
demise but that there is also frequent retention of the products of conception for some time prior to
spontaneous abortion. The macerated fetus is at significant risk for chromosomal abnormality,
whereas the fresh fetal demise without gross congenital anomalies is more often the result of other
etiologies including but not limited to infection, endocrine disorders, abnormal uterine anatomy, and
immunological factors.
Although cytogenetic abnormalities are frequent in early pregnancy, they are much less common
at term. Approximately 1 in 200 live newborns exhibit readily identified aneuploid karyotypes, and
one study estimates that with moderate levels of banding, 0.061% of infants will show unbalanced
structural abnormalities and 0.522% will harbor a balanced rearrangements (17). The rate of unbalanced
karyotypes showing numerical or structural abnormality is much higher in stillbirths, approximating
5–7% overall. Here, too, the risk is greatest for macerated stillbirths, especially in the presence
of congenital anomalies. Cytogenetic abnormalities and associated congenital anomalies are also a
significant factor in neonatal deaths.
The likelihood of survival for a pregnancy with an aberrant karyotype is a reflection of the particular
cytogenetic abnormality and the extent of its deleterious effects on embryonic growth and development.
Davison and Burn (18) examined the likelihood of loss for various chromosomal
abnormalities, confirming a virtual 100% loss for autosomal monosomies and tetraploids. Autosomal
trisomies resulted in a 96.5% loss rate. Although greater than 99% of monosomy X pregnancies
failed, only 11% of sex chromosome trisomies were lost spontaneously. Mosaic and structurally
rearranged karyotypes show intermediate loss rates of 68.8% and 53.4%, respectively (see Table 5).
Although there have been several reports of tetraploid conceptuses and near-complete autosomal
monosomies surviving into the third trimester, these are exceptionally rare.
Summarizing data from several series, Kline and Stein (19) compared the frequency of chromosomal
anomalies of spontaneous abortions and live births (see Table 6).
Summary
These data indicate that the majority of chromosomally abnormal pregnancies fail, that the losses
are selective rather than random, and that the differing survival potential is dependent on the particular
cytogenetic abnormality involved.