FISH is not Suitable as a Standalone Test for Detecting Fetal Chromosomal Abnormalities

Karyotyping and fluorescence in situ hybridization (FISH) detect fetal chromosome abnormalities. The choice between karyotyping and FISH is still debatable. In a developing country, parents face an emotional and economic constraint of a prenatal test. Therefore, the results of karyotyping and FISH were analyzed to determine the percentage of clinically abnormal fetuses which would be missed by using standalone FISH. Amniotic fluid samples from 9033 high-risk pregnancies were subjected to karyotyping and FISH for chromosomes 13, 18, 21, X, and Y. Karyotype and FISH were normal in 8680 (96.1 %) of these samples and 353 (3.9 %) had abnormal karyotypes: 285 (3.2 %) were aneuploidies, also detected by FISH and 68 (0.7 %) were structural chromosomal aberrations not detected by FISH. Out of these 68 structural aberrations, 40 (0.4 %) were balanced rearrangements with no apparent clinical significance and 28 (0.3 %) were unbalanced rearrangements with potential clinical significance. By standalone FISH, 0.3 % clinically-significant samples would have been missed. A 0.2 % risk of procedure-related abortion may be acceptable but a 0.3 % risk of having an abnormal child may not be acceptable to the parents. FISH may be offered as a first test, followed by karyotyping. Although, karyotyping increases the cost, it is preferable to carry this out once an invasive procedure has been opted for, with its accompanying risk of miscarriage.