Pregnancy Associated Protein (PAPP-A)

Why this test?

For possible chromosomal abnormalities screening in the fetus.

To assess the threat of premature termination of pregnancy or miscarriage, predict the course of pregnancy.

In what cases is it prescribed?

When examining pregnant women in the first trimester (the analysis is recommended at 10-13 weeks of pregnancy), especially in the presence of risk factors for the development of pathology:

• age over 35 years;
• miscarriage and severe pregnancy complications in the past;
• chromosomal pathologies, Down's disease or congenital malformations in previous pregnancies;
• hereditary diseases in the family;
• previous infections, radiation exposure, taking drugs in the early stages of pregnancy or shortly before it that have a teratogenic effect (can cause birth defects and fetal abnormalities).

Test information

Pregnancy-associated plasma protein A (PAPP-A) belongs to zinc-containing enzymes (metalloproteinases). During pregnancy, it is produced in large quantities by fibroblasts in the outer layer of the placenta and decidual membrane, and is determined in the maternal bloodstream in the form of a high-molecular protein fraction.

The PAPP-A enzyme cleaves protein fragments from the insulin-like growth factor and increases its biological activity, which ensures full growth and development of the placenta. In addition, it is able to inactivate some enzymes in the blood (trypsin, elastase, plasmin) and modulate the immune response of the mother's body. Its content in the blood increases with the progression of pregnancy and does not significantly depend on such parameters as the gender and weight of the child. Only during the period of intensive formation of the placenta (7-14th week of pregnancy) is there a strong relationship between the level of PAPP-A and the concentration of estradiol. After delivery, PAPP-A rapidly decreases within a few days.

With chromosomal abnormalities with defects in fetal development, the concentration of PAPP-A in the blood decreases significantly from the 8th to the 14th week of pregnancy. The sharpest decrease is observed with trisomies on the 21st, 18th and 13th chromosomes. In Down syndrome, the PAPP-A indicator is an order of magnitude lower than normal. The level of PAPP-A in the mother's blood serum drops even more sharply if the fetus has a genetic pathology with multiple developmental defects - Cornelia de Lange syndrome.

The test is prescribed in combination with the determination of the beta subunit of chorionic gonadotropin and examination of the thickness of the cervical space by ultrasound. This comprehensive examination is recommended for screening for Down syndrome and other fetal chromosomal abnormalities in the first trimester of pregnancy (at 10-13 weeks). After 14 weeks of pregnancy, the value of this indicator as a marker of the risk of chromosomal abnormalities is lost, since the level corresponds to the norm even with pathology.

Low content of PAPP-A in the first trimester indicates an increased risk of pregnancy complications.

Based on the results of this test, a decision is made on the feasibility of prescribing additional methods of fetal examination. At the same time, the level of PAPP-A cannot serve as a criterion for making a diagnosis. In normal pregnancies, the test result can be false positive in 5%, and chromosomal abnormalities of the fetus are detected only in 2-3% of pregnant women with a reduced level of PAPP-A. In the United States, thanks to the use of this test in the first trimester of pregnancy, about 85% of cases of Down syndrome and 95% of Edwards syndrome are detected. If the result is positive, additional examinations are required, including chorionic puncture, amniocentesis with genetic testing of the obtained material.
A minimal amount of PAPP-A protein can be detected in men and non-pregnant women. An increase in PAPP-A is registered after damage to atherosclerotic plaques in acute coronary syndrome, unstable angina. This protein is actively researched as a marker for the prognosis of coronary heart disease, but it has not yet been widely used in cardiology laboratory tests.