Genetic Ultrasound in Women Less than 35

Can Ultrasound Be Used To Identify Fetuses With Down Syndrome?

Early Ultrasound Studies


Until recently, medical studies in which ultrasound evaluation of fetal anatomy has been used to identify fetuses with Down syndrome have focused on individual features of Down syndrome. Individual ultrasound markers which have been studied include the length of the middle bone of 5th digit of the hand, the length of the femur (upper leg bone), the length of the humerus (upper arm bone), length of the foot, the presence of a thick pad of skin behind the neck (nuchal skin fold), the appearance of the kidneys, and bowel. While these studies have been helpful, they did not demonstrate a detection rate for Down syndrome which was greater than maternal Triple Marker serum screening. In addition, no studies focused on examination of the fetal heart, the most frequent birth defect in infants with Down syndrome. The reason for this was because the fetal heart was the most difficult part of the ultrasound examination to perform and interpret.

Color Doppler Ultrasound To Detect Down Syndrome

In 1990, a study was initiated by Dr. DeVore, in collaboration with Dr. Omar Alfi, a Pediatric Geneticist who was the former director of Alfigen, The Genetics Institute, (Pasadena, California),where the study was conducted. The purpose of the study was to determine whether color Doppler ultrasound evaluation of the cardiovascular system could be used to improve the detection rate for Down syndrome as well as other chromosomal abnormalities. The results of the original study were published in the medical journal Obstetrics and Gynecology, the official journal of The American College of Obstetricians and Gynecologists. The results of the study found that examination of the fetus with real-time ultrasound identified 30% of fetuses with Down syndrome, a number which was consistent with prior studies in which multiple organ systems were examined. However, the use of color Doppler ultrasound increased the yield from 29% to 87%. In addition, the detection rate for all abnormal chromosomes, of which Down syndrome is the most common, increased from 36% to 75%. If the patients who were obese in which ultrasound examination was inadequate were removed from the analysis, the detection rate for Down syndrome increased from 87% to 93%. Following the initial report by Dr. DeVore, a more comprehensive study was published in 2000 in the journal of Ultrasound in Obstetrics and Gynecology in which 80 fetuses with Down syndrome and 2,000 controls were examined. This study demonstrated the following:

1. Using a B-Mode ultrasound, without examining the fetal heart, detected 60% of fetuses with Down syndrome.

2. Using B-Mode ultrasound and evaluating the four-chamber view of the heart for disproportion, 75% of fetuses with Down syndrome were detected.

3. Using B-Mode ultrasound plus color Doppler ultrasound to examine the fetal heart in greater detail identified 91% of fetuses with Down syndrome.

4. Genetic Ultrasound, when practiced by physicians with special training in this area, is a useful tool to adjust the risk for Down syndrome.

At the present time Genetic Ultrasound is an accepted methodology that can be used to determine the risk for Down syndrome. A recent publication from the American College of Obstetricians and Gynecologists entitled the ACOG Practice Bulletin, “Ultrasound in Pregnancy” (Num 58, December 2004), states:

“A second-trimester specialized ultrasound examination may be targeted to detect fetal aneuploidy (Down syndrome). This type of examination has been offered in some centers for the past several years and is aimed at the detection of a range of minor anatomic features associated with an increased risk for fetal aneuploidy…. The standard examination is less likely to detect the minor anatomic features associated with aneuploidy.”

The Use of Genetic Ultrasound to Decrease the Risk for Down Syndrome in Women Less Than 35 Years of Age

Genetic Ultrasound can be used in two clinical situations in women less than 35 years of age. With the inception of maternal serum screening using the Triple Marker test, approximately 5% of women less than 35 years of age were identified to be at high risk for Down syndrome. Many of these women did not desire genetic amniocentesis and often asked if another non-invasive test could be performed to re-evaluate their risk. Genetic Ultrasound is a great solution for this problem. The reduction in risk depends upon how accurate the Genetic Ultrasound detects Down syndrome. For example, if B-Mode and color Doppler are used, the detection rate of Down syndrome is 91%, as described above. Therefore, if a woman less than 35 years of age is informed that she has an increased risk for Down syndrome following maternal serum screening, then her final risk can be reduced if the Genetic Ultrasound is normal. The following graph illustrates the reduction in risk for Down syndrome based an abnormal risk following maternal serum screening.

This graph illustrates the change in risk for Down syndrome after a normal Genetic Ultrasound. The risk in which amniocentesis is usually offered is 1 in 270. Therefore, if the risk is between 1 in 30 and 1 in 270 following maternal serum screening (blue line), then a normal Genetic Ultasound increases the risk above the cutoff of 1 in 270 (orange line).

The Use of Genetic Ultrasound to Increase the Detection Rate for Down Syndrome in Women Less Than 35 Years of Age

Another use of Genetic Ultrasound is to increase the detection of Down syndrome in this group of patients. In a paper by DeVore and Romero, they examined the cost-effectiveness of increasing the detection rate of Down syndrome in women less than 35 years of age who had a MODERATE RISK for Down syndrome following the Triple Marker maternal serum screening test. The following graph illustrates this principle.

 

While this graph may at first appear to be complicated, let us examine it step-by-step. The left upper panel indicates that 75% of fetuses with Down syndrome are born to women less than 35 years of age. Even though the risk in these women is low, they have more children than women over 35. The upper right panel illustrates that Triple Marker serum screening only identifies 49% of fetuses with Down syndrome. The right lower panel demonstrates that the HIGH RISK group contains the 49% of fetuses with Down syndrome. However, the MODERATE RISK group comprises 17.2% of the women and contains an additional 32% of fetuses with Down syndrome. This group of women has a risk for Down syndrome following their Triple Marker screening test that would be reported to be between 1 in 191 and 1 in 1,000. Traditionally, these women are informed that their triple marker test is "normal." It is this group that should be offered Genetic Ultrasound. If the Genetic Ultrasound is abnormal, then they would be offered amniocentesis. The left lower panel demonstrates that If there is a 90% detection rate for Down syndrome then the overall detection rate for Down syndrome would increase from 49% to 78%. This is 9% higher than the QUAD screen.



The following graph illustrates the strategy for testing women less than 35 years of age who undergo Triple-Marker serum screening and wish to use Genetic Ultrasound to optimize the detection rate of Down Syndrome. This would be specifically applicable in California where Triple-Marker Screening is mandated by state law.

 

 

This illustrates the options for women less than 35 once they receive the results of their Triple-Marker screening test. If they were High Risk, then amniocentesis would be offered. If they were Moderate Risk, they would undergo Genetic Ultrasound and be offered genetic amniocentesis only if an abnormal ultrasound finding was identified. If they were Low Risk, then no additional testing would be offered. Using this approach, 78% of Down syndrome fetuses would be detected.