Rapid Prenatal Diagnosis: Some straightforward answers to common questions

Using fluorescent DNA probes, the 13, 18, 21, X, and Y chromosomes in each cell can be counted.  Unlike conventional chromosome analysis, which requires cells that are actively growing and dividing and takes 7-14 days, this rapid technique can be used on uncultured cells obtained directly from amniotic fluid. While not all chromosome abnormalities can be identified simply by counting specific chromosomes within a cell, the majority of the most common abnormalities of chromosome number, including Down syndrome (trisomy 21), trisomy 18, trisomy 13, Klinefelter syndrome (47,XXY), triple-X syndrome (47,XXX), Turner syndrome (45,X) and 47,XYY can be reliably determined. The technique is sometimes known as interphase FISH, which stands for fluorescent in situ hybridization. Our laboratory uses the AneuVysion Test which has been cleared by the FDA for this purpose.

Sometimes, when it is suspected that the fetus may have a chromosome abnormality, important pregnancy management decisions need to be made quickly. The following are some of the situations in which a rapid assay may be helpful.

• Prenatal chromosome diagnosis is indicated, but the pregnancy is more than 20 weeks gestation.

• An ultrasound finding discovered in the third trimester that suggests the fetus has an extremely serious condition, such as trisomy 13 or trisomy 18.

• Maternal age, serum screening, or sonographic findings indicate a very high risk for an autosomal trisomy.

• Extreme anxiety is exhibited by a patient about whether the fetus has a chromosome abnormality, for example, in a case where a chromosome problem was discovered in a previous pregnancy.

In certain clinical situations, the benefits of the rapid FISH assay include:

• Obtaining information prior to 24 weeks gestation so that a patient can plan the remainder of the pregnancy,

• Knowing the chromosome status of a baby prior to an impending delivery so that the physician can manage the delivery appropriately; for example, avoiding an unnecessary cesarean section for a baby with trisomy 18,

• Being able to quickly reassure an extremely anxious patient that the fetus does not have Down syndrome, trisomy 18, trisomy 13, or one of the sex chromosome aneuploidies.

What are limitations of rapid prenatal diagnosis?

• This analysis does not screen for all chromosome abnormalities, only the most common abnormalities of chromosome number. Prenatal FISH is not designed to detect chromosome mosaicism, duplications, deletions, or structural rearrangements.

• Due to the nature of rapid FISH analysis, irreversible therapeutic decisions should not be made on FISH results alone.

• Neither FISH nor conventional cytogenetics identifies all birth and/or developmental abnormalities.

• An additional 5-10ml of clear amniotic fluid is required for the rapid FISH assay, which is only done in conjunction with conventional chromosome studies.

• The rapid FISH assay may not be informative if the sample quantity is insufficient or the sample quality inadequate (i.e., contains maternal blood). Problems in slide preparation can also render the assay uninformative.
  

• Most laboratories, including our own, ask for as much advance notice as possible when these studies are desired, in order to minimize transport delays and laboratory workflow delays.

• Our laboratory employs reagents that are cleared by the FDA as an in vitro diagnostic test.  However, prenatal FISH is not intended to be used for making clinical decisions as a stand-alone test.

• Most insurers consider this a covered medical expense when there is an accepted medical indication for rapid prenatal diagnosis.

• While prenatal FISH is highly accurate, errors in diagnosis occasionally occur.  Both physicians and patients need to be aware of this.

• Informed consent from the patient must be obtained before any prenatal testing, including FISH.