First Trimester Screening And Cell-free Fetal DNA

Identifying pregnancies at risk for chromosomal abnormalities is an extremely important aspect of prenatal care.  Typically chromosomal analysis is done for Trisomy 21 (Down Syndrome), as well as Trisomy 18 and 13.  This testing or screening has undergone tremendous strides with regards to techniques, risk reduction, sensitivity and specificity.  In the not so distant past, identifying a pregnancy with concerns for genetic abnormalities involved tests that had shortcomings with regard to sensitivity, (the ability of a test to detect disease) as well as specificity, (the ability of a test to classify accurately as disease-free).  Because of these shortcomings, results were associated with a high number of erroneous positive and negative results.

In general, when screening tests results are abnormal, further analysis is required.  To further analyze, diagnostic testing or direct analysis of fetal cells is recommended.  In the obstetrical world, this is accomplished via an invasive procedure known as amniocentesis, (removal of fetal cells found in the amniotic fluid, from a needle placed through the maternal abdomen and into the uterine cavity).  Thankfully, secondary to new advancements, the number of patients requiring further evaluation is decreasing.  Amniocentesis is the only way to 100% determine fetal chromosomal abnormalities but the number of patients now requiring such an invasive procedure has decreased significantly.  This is because of improved screening technology.

In the past, screening involved analyzing maternal blood for different amounts of particular proteins or hormones that at particular levels would be indicative or associated with chromosomal anomalies.  Once isolated, the proteins/hormones were measured and then simply plotted or analyzed as a statistical measurement compared to other pregnant women at the same gestational age, providing a likelihood of anomaly.  In other words, your test results were determined as a probability, not as fact; i.e. your results were interpreted as “1 in 50” or as “1 in 10,000” chance of abnormality.


Until recently, the most frequently offered test for chromosomal anomalies was the First -Trimester Screening test. This test incorporates an ultrasound for “nuchal translucency” which is a measurement of the thickness of the space behind the fetal neck; additionally a blood test is taken for measurement of two maternal serum levels for free B-Hcg as well as level for pregnancy-associated plasma protein A, (PAPP-A).  The results of these two analytes, plus the nuchal translucency is analyzed with other factors such as maternal age, which then provides a risk estimate for a patient.  Results will be reported as a risk of “1 in 500” or “1 in 2,500” for instance.  This test has a detection rate for Down Syndrome of 82-87%.


Cell-free fetal DNA has changed all of this.  Now we can actually perform a direct analysis of  the fetal DNA circulating in maternal blood.  There are several companies who provide this service and your practitioner, using a particular company, may refer to this testing under different names. But the technology is essentially the same.  A pregnant patient, as early as 10 weeks, may have her blood drawn, as she would for any other blood draw; i.e. no needles placed abdominally as in an amniocentesis.  By that time, the baby’s DNA, circulating in the mother’s blood, is able to be collected, separated, and analyzed directly.  This test is NOT perfect.  Separating fetal from maternal DNA may still prevent 100% accuracy in results.  For trisomy 21 (Down syndrome) the sensitivity is 99%.   However for Trisomy 13 the sensitivity decreases to 91%.  Regardless, the ability to actually analyze directly your baby’s genetic material is a remarkable advancement.

It is important to consider that this advancement is only for CHROMOSOMAL abnormalities, or abnormalities that arise from the genetic material of the baby.  THIS WILL NOT DETECT CONGENITAL DEFECTS.  LIKEWISE IT WILL NOT SCREEN FOR ALL CHROMOSOMAL ABNORMALITIES BUT ONLY FOR THOSE THAT WERE TESTED.  

In a perfect world, when a patient tests “positive” for a disease, it would be great to know 100% that the patient is truly positive.  But this is not a perfect world and that isn’t always the case.  Sometimes, the test may be wrong.  Remember, this is only a screening test:  it is not a diagnostic test.  Abnormal results require diagnostic evaluation.

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