Interpretive Handbook

Chromosomal abnormalities may result in malformed fetuses, spontaneous abortions, or neonatal deaths. Estimates of the frequency of chromosome abnormalities in spontaneous abortuses range from 15% to 60%.

Chromosome studies of products of conception (POC) may provide useful information concerning the cause of miscarriage and, thus, the recurrence risk for pregnancy loss and risk for having subsequent children with chromosome anomalies.

Chromosome analysis of the stillborn infant or neonate (autopsy) may be desirable, particularly if there is a family history of 2 or more miscarriages or when malformations are evident. For neonatal cases, peripheral blood is the preferred specimen for chromosome analysis (CMS/8696 Chromosome Analysis, for Congenital Disorders, Blood).

Autopsy:

-Second-tier testing for chromosomal abnormalities

-Follow-up testing when chromosomal analysis and other studies on peripheral blood are inconclusive or when peripheral blood quality is poor or sampling is not possible

Products of Conception or Stillbirth:

-Diagnosing chromosomal causes for fetal death

-Determining recurrence risk for future pregnancy losses

The finding of a chromosome abnormality may explain the cause of a miscarriage or stillbirth, particularly when the chromosome results show aneuploidy or an unbalanced structural rearrangement.

Some of the chromosome abnormalities that are detected in these specimens are balanced (no apparent gain or loss of genetic material) and may not be associated with birth defects, miscarriage, or stillbirth.

For balanced chromosome rearrangements, it is sometimes difficult to determine whether the chromosome abnormality is the direct cause of a miscarriage or stillbirth. In these situations, chromosome studies of the parents' peripheral blood may be useful to determine if an abnormality is familial or de novo.  

De novo, balanced rearrangements can cause miscarriages or stillbirth by producing submicroscopic deletions, duplications, or gene mutations at the site of chromosome breakage.

A normal karyotype does not rule out the possibility of birth defects, such as those caused by submicroscopic cytogenetic abnormalities, molecular mutations, and environmental factors (ie, teratogen exposure).

Due to bacterial contamination or nonviable cells, we are unable to establish a viable culture 20% of the time. In these cases, the specimen cannot be used for chromosome analysis, so the FISH aneuploidy test is automatically initiated. While the FISH test is not as comprehensive as a chromosome analysis, it can provide information with regard to many of the most common numeric abnormalities in spontaneous miscarriage and stillbirth.

Interfering factors

Technical:

-Lack of viable cells or bacterial contamination (this occurs in approximately 20% of spontaneously aborted products of conception)

-A long delay between fetal death and the miscarriage

-Excessive transport time

-Exposure of the specimen to temperature extremes

Biological:

-Subtle structural chromosomal abnormalities can occasionally be missed

-Culturing of maternal cells rather than fetal cells

-Chromosome mosaicism may be missed due to statistical sampling error (rare)

46,XX or 46,XY. No apparent chromosome abnormality.

An interpretive report will be provided.

Dewald GW, Michels VV: Recurrent miscarriages: cytogenetic causes and genetic counseling of affected families. Clin Obstet Gynecol 1986;29:865-885