Second Trimester Screening
Second Trimester Screening
A screening test identifies fetuses (unborn babies) with an increased risk of having birth defects like Down syndrome. Unlike CVS or amniocentesis, screening tests do not diagnose, but rather provide a risk estimate specific to the pregnancy. New screening tests have been introduced to enhance detection of birth defects and to reduce follow-up procedures.
First trimester screening performed from 11-13 weeks 6 days is a combination of a blood test to measure two pregnancy proteins and a special ultrasound that measures the nuchal translucency (fluid accumulation at the back of the fetal neck). The test has a 91% detection rate for Down syndrome and a 97% detection rate for Trisomy 18/13.
For those women presenting during the second trimester of pregnancy, the following three screening tests are available: AFP/freeBeta, triple screen and quad screen. All these tests measure the levels of proteins in maternal blood. GeneCare offers the most effective second trimester screening tool, known as the AFP /free Beta screen. AFP/freeBeta uses the most sophisticated analysis to significantly improve detection of Down syndrome, trisomy 18/13, and open spine and skull defects. Triple and quad tests have the lowest detection rates. AFP/freeBeta screen can be performed as early as 13 weeks 4 days without loss of detection while the triple and quad screens must be performed after 14 weeks
Detection Rate
The two tables below document the higher accuracy of AFP/free Beta screening over the triple screen. Quad test detection rates are not available because USA Prospective Quad Studies have not been published.
Table 1: Performance of the AFP/freeBeta Screen between 13w4d and 22w3d gestation.
| IPR* | Detection Rate | Yield** | |
|---|---|---|---|
| ONTD*** | 2.7% | 98% | 25 |
| Down syndrome | 2.8% | 80% | 25 |
| Trisomy 18/13 | 0.3% | 70% | 6 |
| Total = | 5.6% |
Table 2: Performance of triple screen (MSAFP/hCG/estriol) between 16 and 20 weeks gestation.
| IPR* | Detection Rate | Yield** | |
|---|---|---|---|
| ONTD*** | 5.0% | 85% | 42 |
| Down syndrome | 6.5% | 60% | 80 |
| Trisomy 18/13 | 0.5% | 60% | 16 |
| Total = | 12% |
* Initial Positive Rate (percentage of women identified at increased risk for an abnormality)
** Number of amniocenteses necessary to identify one affected fetus
*** ONTD = open spine and skull defects
NOTE: Detection rates for the triple screen decrease significantly at gestations before 16 and after 20 weeks.
Comparison Criteria
The quality or efficacy of a screening program is judged by multiple factors:
Detection Rate
The detection rate is defined as the percentage of affected fetuses that are identified as high risk by the test. Screening programs try to maximize this factor.
The second trimester AFP/free beta hCG screen has a higher detection rate for Down syndrome (80%), Trisomy 18/13 (70%) and ONTD (98%) compared to the triple screen which has a 60% detection rate for Down syndrome and Trisomy 18/13 and 85% detection rate for ONTD's.
Screen Positive Rate
The screen positive rate (SPR) is the percentage of women being screened reported to have an increased risk for Down syndrome and/or Trisomy 18/13. Screening programs try to minimize this factor.
The positive rate from second trimester AFP/freeBeta screening is less than half that of the triple screen (5.6% versus 7.6%). This statistic translates into fewer anxious patients, reduced medical costs, less coordination effort by the physician's office, and fewer diagnostic amniocenteses.
Yield
Yield is the number of diagnostic procedures (CVS or amniocentesis) required to identify an affected fetus. Screening programs try to decrease the number of diagnostic tests needed to identify the same number of affected fetuses.
The AFP/freeBeta screen has a lower yield compared to the triple screen. This translates to a lower number of amniocentesis performed after the second trimester screen thereby decreasing patient anxiety.
Additional Remarks:
Open Spine and Skull Defect Screening
Birth defects like open neural tube defects (open spine and/or skull defects) and open abdominal defects usually occur without a family history and are not associated with maternal age. AFP (alpha-feto protein) is a protein in the mother's blood used to detect fetuses with ONTDs, such as spina bifida. Fetuses with ONTDs secrete more AFP, which crosses the mother's placenta and enters her bloodstream. This causes an elevation in the level of AFP in maternal blood during the second trimester. The AFP detection rate for ONTDs by the AFP/freeBeta screen is dramatically improved over that of the triple screen (98% versus 80-85%). This is accomplished by:
- Generating a patient-specific risk from sophisticated statistical analysis.
- Using true patient-specific risk cut-offs, as opposed to a multiple of the median (MoM, compares a woman's values to median values taken from the general population), to identify a positive screen. This generates a more accurate risk for each patient by comparing her risk to other women with a similar background.
- Incorporating additional information, such as family history and geographical demographics, into the risk calculation to better define each subpopulation being screened.
Adjusted Down Syndrome Screening in Hispanics
A recent paper in Prenatal Diagnosis documents a higher than expected frequency of Down syndrome among Hispanic liveborn children. Overall, the paper confirmed a 20% increase in Down syndrome in Hispanics compared to non-Hispanics. This finding has implications for prenatal screening and diagnosis. The adjustment for maternal serum screening programs is straightforward: before screening, the maternal-age rate for Down syndrome should be increased by 20% in Hispanic women. This adjustment has been made in GeneCare's screening program and will ensure the most accurate risk assessment across all populations.
Efficiency Comparison
In light of the above data, it is clear that AFP/freeBeta is a far more effective second trimester screening protocol than triple or quad screens. It detects substantially more affected fetuses, while requiring half as many amniocenteses. Patient anxiety amniocentesis and costs, are dramatically reduced.
In Europe, the number of labs offering triple screen has decreased to a small minority because the world literature shows AFP/freeBeta is significantly more effective, less expensive, and is not limited to 16-20 weeks gestation.
There are no documented reasons for physicians not to switch to AFP/freeBeta screening. Physicians throughout the U.S. and around the world provide AFP/freeBeta screening, so this option is available to all patients.
Second Trimester Markers
Alpha-fetoprotein
Alpha-fetoprotein (AFP) is the best marker known for detection of open neural tube defects (ONTDs). It is elevated in the blood of women carrying fetuses with ONTDs. Conversely, AFP tends to be lower in the blood of women carrying fetuses with Down syndrome and Trisomy 18/13.
FreeBeta hCG
FreeBeta is the only biochemical marker that can be used in both the first and second trimester. In both trimesters, free Beta hCG is elevated in the blood of women carrying fetuses with Down syndrome. In general, the average level of hCG in the blood of women carrying an unaffected fetus is 1.0 MOM (multiple of median, MOM for short, is a comparison of the patient's blood values to the normal range). On the other hand, when a fetus is affected with Down syndrome, the average free beta hCG level is 2.69 MOM.
The level of free beta hCG is decreased in the blood of women carrying a fetus affected with Trisomy 18/13 (average of 0.20 MOM in an affected fetus compared to an unaffected fetus average 1.0 MOM). This makes free Beta hCG the most specific and sensitive marker for Down syndrome and Trisomy 18/13.
There is a misconception that the use of three markers provides better detection than two markers. On the contrary, the combination of free Beta and AFP achieves a 21-24% higher Down syndrome detection rate at a lower false positive rate than the triple screen. In summary, the scientific literature has documented the AFP/free Beta screen is the most sensitive (highest detection rate) and specific (lowest false positive rate) Down syndrome, Trisomy 18/13, and ONTD screening test.
Benefits of screening performed by GeneCare
GeneCare uses several innovative approaches to reduce the overlap between affected and unaffected fetuses and raises detection and yield and lowers SPR:
- Dried blood testing stabilizes the blood protein, eliminates sample degradation and guarantees the patient's sample is representative of her true biological state.
- Patented assays with the highest documented specificity and sensitivity most accurately measure the AFP and freeBeta concentrations on dried filter paper.
- Unlike large general laboratories, no default data is ever used i.e. if patient information (such as weight, family history, etc.) is not provided; it is obtained from the referring physician prior to analysis.
- Unlike some other laboratories, positive family history is considered in assessing the patient's prior risk for Down syndrome and Trisomy 18/13.
- Improved statistical methods are applied by GeneCare to generate a true patient-specific risk for Down syndrome, Trisomy 18/13 and ONTD's.
- The detection rate is increasedand SPR decreased by obtaining follow-up information on the outcome of pregnancies tested in our laboratory. Physicians and patients should be aware that only labs with outcome data can quote their detection and screen positive rates.
Information provided on this site is for information purposes ONLY. This should not be used as a substitute for professional medical advice, treatment or diagnosis.