Chromosome Analysis, Amniotic Fluid With Reflex to SNP Microarray (Reveal®)

Amniotic fluid, fetal urine, or cystic hygroma fluid

20 to 30 mL (15 to 20 mL for early amniocentesis)

5 mL (Minimum volume may delay results due to fewer cells available for culture.)

Sterile plastic conical tube

The patient preferably should have had ultrasound studies (to verify fetal life, detect multiple gestation, confirm gestational age, localize placenta).

The chromosome analysis determines fetal karyotype. A normal chromosome analysis will reflex to a high-resolution SNP microarray analysis targeting 2.695 million copy-number and allele-specific genome sites. The SNP assay will detect chromosomal imbalances that could be associated with developmental delay/congenital anomalies. It provides possible detection of uniparental disomy of any chromosome, the percent and location of homozygosity, including the degree of identity by descent.

Although the overall culture success rate is reported as >99%, culture failure can result. Reasons include (but are not limited to) lack of amniocytes in the fluid and contamination of the fluid with bacteria or yeast. For the SNP assay, it does not detect balanced rearrangements, low-level mosaicism (<10%), marker chromosomes that only contain heterochromatin or tetraploidy.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

In situ cell culturing of amniocytes to investigate numerical and/or structural chromosome abnormalities. A normal chromosome analysis will reflex to SNP microarray analysis using the Cytoscan® HD platform, which uses more than 743,000 SNP probes and 1,953,000 NPCN probes with a median spacing of 0.88 kb.

Additional biochemical or molecular tests may be performed on the cultured amniocytes.

Fetal loss rate is considered to be 0.5% at 14 to 18 week sampling and 2% to 3% at 10 to 13 weeks.¹ Chorionic villus sampling (CVS) may be safer than early amniocentesis for early prenatal diagnosis of cytogenetic abnormalities.^2,3

The risk of miscarriage with CVS is 1% to 1.5%, but the risk of maternal infection appears to be higher with CVS than with amniocentesis.⁴ Cytogenetic analyses using such samples allow for early gestational testing based on a 10- to 11-week placental biopsy and a five-day cytogenetic study. Most failures are due to an inappropriate biopsy containing only maternal decidua. Chromosomal aberrations were found in 4.6% of fetuses in women older than 38 to 40 years. Trisomy 21 was the most common abnormality (62%). Klinefelter syndrome (11%), Edwards syndrome, and trisomy 18 (11%) were the next most frequent in the cases of advanced maternal age.

Prenatal diagnosis is possible for more than 1000 inherited diseases. Most are inherited in an autosomal recessive manner. Antenatal diagnosis using gene probes has become available for cystic fibrosis, muscular dystrophy, sickle cell anemia, hemophilia, and many other genetic abnormalities. This can be done from either cultured amniotic fluid cells or chorionic villus sampling.⁵