Generality
PAPP-A is a high molecular weight glycoprotein, which can be measured in blood as an early screening test for Down syndrome .
The acronym PAPP-A is an acronym for Pregnancy-associated plasma protein A, or plasma protein A associated with pregnancy .
What's this
The pregnancy-associated plasma protein A (PAPP-A) is a high molecular weight glycoprotein of placental origin (720-850 kD).
This protein is mainly produced in the trophoblast syncytium (ie the element of embryonic development necessary for nesting in the uterus) and is released into the maternal circle.
The PAPP-A allows to evaluate the risk that a fetus can carry chromosomal abnormalities, such as trisomy 21 (Down syndrome).
Why do you measure
The dosage of PAPP-A - together with that of Beta-HCG (β-unit of the human chorionic gonadotropin - β-hCG ), and an absolutely harmless ultrasound examination ( Nucale Translucency ) - allows us to quantify the risk that the fetus is affected by chromosomal abnormalities, in particular trisomy 21 (Down syndrome) or trisomy 18 (Edwards syndrome) ; at the same time, it allows to identify particular risk situations for some anatomical or placental anomalies.
All this is possible already during the first trimester of gestation; in particular, according to the guidelines, the optimal period for the execution of these exams is between the eleventh and thirteenth week of pregnancy.
Indications of the PAPP-A test
The association of the bi-test on maternal venous blood (PAPP-A and β-hCG) with the examination of nuchal translucency, is indicated for:
- Pregnant women under the age of 35 who wish to evaluate early the risk of the fetus suffering from Down syndrome (trisomy 21), and then decide whether to undergo more invasive tests, such as amniocentesis or chorionic villus sampling;
- Pregnant women over the age of 35 who wish to assess the risk more precisely, to decide whether or not to avoid undergoing invasive prenatal diagnostic methods (amniocentesis or chorionic villus sampling), recommended by international protocols because of the associated high risk at the age.
Normal values
In pregnancies, the concentration of PAPP-A normally increases with gestational age until birth.
After giving birth, the amount of protein found in the circulation decreases rapidly with a half-life of 3-4 days.
PAPP-A Alta - Causes
PAPP-A Low - Causes
Low levels of PAPP-A in serum have a good predictive value in the detection of chromosomal alterations affecting the fetus. In particular, the plasma protein A associated with pregnancy can be reduced in the presence of trisomy 21 (Down syndrome) or trisomy 18 (Edwards syndrome) .
The decrease in the concentration of PAPP-A in the maternal serum is also observed in the presence of a risk of spontaneous interruption of pregnancy, even in the absence of fetal aneuploidies (ie numerical anomalies of the chromosomes).
In this sense, low levels of this protein can be indicative of:
- Placenta problems (eg detachment);
- Preeclampsia;
- Preterm birth;
- Fetal death.
How to measure it
The combined test (bi-test ) consists of a blood sample, to which the future mother must be subjected; the result of this examination is then integrated with that of fetal ultrasound.
The analyzes of PAPP-A are performed during the first trimester of pregnancy, as part of the global assessment of the risk of fetal malformations (trisomy 21 and trisomy 18); in this context, they are carried out in combination with other exams (such as ultrasonography of nuchal translucency) that contribute to the elaboration of the risk calculation.
Preparation
Before undergoing the examination, it is necessary to observe a fast of at least 8 hours, during which a small quantity of water is allowed.
Interpretation of Results
In the first trimester of gestation, in the case of a fetus with Down syndrome, the levels of PAPP-A tend to be lower than expected.
Low PAPP-A = high risk of Down syndrome
The concentrations of plasma protein A associated with pregnancy in the maternal serum grow rapidly from the beginning of pregnancy.
The researchers noted that in the presence of a fetus with Down Syndrome, the levels of PAPP-A tend to be almost always lower than expected. However, to minimize the risk of obtaining false positive or negative results, the dosage of PAPP-A must necessarily be supplemented by other tests.
- In cases of trisomy 21, during the first trimester, the concentration in the maternal serum of the β-hCG fraction is higher than in the pregnancy with the euploid fetus (not affected by trisomy 21), while the PAPP-A is lower than normal.
- As regards nuchal transluscence, the examination evaluates the space between the skeleton and the body surface of the fetus at the level of the cervical vertebrae. If this space increases compared to the expected value for the gestation period considered, it is indicative of chromosomal abnormalities or other fetal pathologies.
Combining maternal age, biochemical markers and nuchal translucency, the estimated detection rate for trisomy 21 reaches about 90-95%, with a false positive rate of 3-5%. This means that - statistically speaking - this early screening is able to identify on average 90-95 effective cases of Down syndrome out of 100, while in 3-5% of cases it diagnoses a healthy fetus as suffering from Down syndrome.
Despite the non-optimal sensitivity and specificity, such an early screening allows the selection of pregnant women to start subsequent invasive diagnostic tests (chorionic villus sampling, amniocentesis), which are more precise but burdened with a small risk of abortion (0.5 -1%).
Apart from PAPP-A and the various early screening tests in the first trimester, there are several biochemical markers able to quantify the risk of Down syndrome also in the second trimester of gestation. In this case, the serum values of maternal alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol (uE3) and possibly inhibin A (INH-A) are evaluated:
the risk of carrying a child with Down syndrome in the womb is considered high when the mother has high blood levels of inhibin A and human chorionic gonadotropin, associated with a reduction in estriol and alpha-fetoprotein concentrations.
To learn more: Tri-test
When undergoing a screening test for chromosomal abnormalities it should be noted that:
- If the risk of illness is reduced, it does not mean that it is zero.
- If the risk of illness is high, this does not necessarily imply that the fetus is affected by a chromosomal anomaly; rather, it simply means that the risk is high enough to justify a clarifying invasive examination (villocentesis or amniocentesis).
- Therefore a pregnant woman who wishes to have absolute certainty about the absence of chromosomal anomalies, and accepts the small risk associated with these diagnostic procedures, is directly directed to amniocentesis or villocentesis, bypassing the screening tests.
NOTE : the association between bi-tests on venous-maternal blood (PAPP-A - β-hCG) and nuchal translucency, provides an ESTIMATE of the probability that the fetus is affected by Down syndrome. The test cannot make a diagnosis, but expresses a probability.
The result of the PAPPA-a and of the other tests is generally communicated as an estimate of the probabilities (for example 1 possible pathological case out of 1, 000 or a possible pathological case out of 100) and not as a positive or negative result.
The probability index is the result of computer processing of laboratory, ultrasound and amnestetic data (age, weight, mother's race, etc.); if its value is between 1/1 and 1/250 the probability that the child is affected by Trisomy 21 is considered high. If the denominator number is greater than 250 (<1/250) the probability is considered low.
Based on this estimate, the expectant mother will decide whether or not to undergo invasive tests (amniocentesis, chorionic villus sampling); fortunately, in most cases these tests will show the total absence of complications.
