PAPP-A (Pregnancy-associated plasma protein-A)

PAPP-A (Pregnancy-associated plasma protein-A)

Determination method Immunoassay.

Test material Blood serum

Home visit available

Pregnancy-associated plasma protein-A. In prenatal screening in the first trimester of pregnancy, it is a risk marker for Down syndrome and other chromosomal abnormalities of the fetus.

PAPP-A is a high molecular weight glycoprotein (m.v. about 800 kDa). During pregnancy, it is produced in large quantities by the trophoblast and enters the maternal circulation system; its concentration in the mother's blood serum increases with increasing gestational age. Based on its biochemical properties, PAPP-A is classified as a metalloprotease. It has the ability to break down one of the proteins that binds insulin-like growth factor. This causes an increase in the bioavailability of insulin-like growth factor, which is an important factor in fetal development during pregnancy. It is assumed that PAPP-A is also involved in the modulation of the maternal immune response during pregnancy. A similar protein is also present in low concentrations in the blood of men and non-pregnant women. The physiological role of PAPP-A continues to be investigated.

A number of serious clinical studies indicate the diagnostic significance of PAPP-A as a screening marker for the risk of fetal chromosomal abnormalities in the early stages of pregnancy (in the first trimester), which is fundamentally important in the diagnosis of chromosomal abnormalities. The level of PAPP-A is significantly reduced in the presence of trisomy 21 (Down syndrome) or trisomy 18 (Edwards syndrome) in the fetus. In addition, this test is also informative in assessing the threat of miscarriage and termination of pregnancy in the short term.

An isolated study of PAPP-A level as a risk marker for Down syndrome has diagnostic value starting from 8–9 weeks of pregnancy. In combination with the determination of beta-hCG (human chorionic gonadotropin), the determination of PAPP-A is optimally carried out at about 12 weeks of pregnancy (11 - 14 weeks). After 14 weeks of pregnancy, the diagnostic value of PAPP-A as a risk marker for Down syndrome is lost.

It has been established that the combination of this test with the determination of the free beta subunit of hCG (or total beta hCG), ultrasound data (nuchal translucency thickness), and assessment of age-related risk factors significantly increases the effectiveness of prenatal screening for Down syndrome in the first trimester of pregnancy, bringing it to 85 - 90% detection rate for Down syndrome with 5% false positive results. The study of PAPP-A as a biochemical marker of congenital and hereditary pathology in the fetus in combination with the determination of hCG at 11 - 13 weeks of pregnancy is currently included in the scheme of screening examinations of pregnant women by Order of the Moscow Department of Health No. 144 of April 4, 2005. first trimester.

Detection of deviations in the levels of biochemical markers in the mother’s blood is not an unconditional confirmation of fetal pathology, but, in combination with the assessment of other risk factors, is the basis for the use of more complex special methods for diagnosing fetal abnormalities.

Limits of detection: 0.03 mU/ml-100 mU/ml

The test will allow your doctor to:

• Determine the likelihood of fetal chromosomal abnormalities;
• Predict the course of pregnancy;
• Assess the risk of miscarriage.

The study is recommended for:

• pregnancy in the first trimester (10-13 weeks);
• pregnancy for women over 35 years of age;
• habitual miscarriage and other complications of previous pregnancies;
• hereditary diseases in the family;
• past infections;
• taking medications in the early stages of pregnancy or shortly before it;
• radiation exposure;
• chromosomal pathologies, Down's disease or congenital malformations in previous pregnancies.

Method:

Enzyme-linked immunosorbent assay (ELISA).

Material for research:

Blood serum.

Pregnancy-associated plasma protein-A. In prenatal screening in the first trimester of pregnancy, a risk marker for Down syndrome and other chromosomal abnormalities of the fetus.

PAPP-A is a high molecular weight glycoprotein (m.v. about 800 kDa). During pregnancy, it is produced in large quantities by the trophoblast and enters the maternal circulation system; its concentration in the mother's blood serum increases with increasing gestational age. Based on its biochemical properties, PAPP-A is classified as a metalloprotease. It has the ability to break down one of the proteins that binds insulin-like growth factor. This causes an increase in the bioavailability of insulin-like growth factor, which is an important factor in fetal development during pregnancy. It is assumed that PAPP-A is also involved in the modulation of the maternal immune response during pregnancy. A similar protein is also present in low concentrations in the blood of men and non-pregnant women. The physiological role of PAPP-A continues to be investigated.

A number of serious clinical studies indicate the diagnostic significance of PAPP-A as a screening marker for the risk of fetal chromosomal abnormalities in the early stages of pregnancy (in the first trimester), which is fundamentally important in the diagnosis of chromosomal abnormalities. The level of PAPP-A is significantly reduced in the presence of trisomy 21 (Down syndrome) or trisomy 18 (Edwards syndrome) in the fetus. In addition, this test is also informative in assessing the threat of miscarriage and termination of pregnancy in the short term.

An isolated study of PAPP-A level as a risk marker for Down syndrome has diagnostic value starting from 8–9 weeks of pregnancy. In combination with the determination of beta-hCG (human chorionic gonadotropin), the determination of PAPP-A is optimally carried out at about 12 weeks of pregnancy (11 - 14 weeks). After 14 weeks of pregnancy, the diagnostic value of PAPP-A as a risk marker for Down syndrome is lost.

It has been established that the combination of this test with the determination of the free beta subunit of hCG (or total beta hCG), ultrasound data (nuchal translucency thickness), and assessment of age-related risk factors significantly increases the effectiveness of prenatal screening for Down syndrome in the first trimester of pregnancy, bringing it to 85 - 90% detection rate for Down syndrome with 5% false positive results. The study of PAPP-A as a biochemical marker of congenital and hereditary pathology in the fetus in combination with the determination of hCG at 11 - 13 weeks of pregnancy is currently included in the scheme of screening examinations of pregnant women by Order of the Moscow Department of Health No. 144 of April 4, 2005. first trimester.

Detection of deviations in the levels of biochemical markers in the mother’s blood is not an unconditional confirmation of fetal pathology, but, in combination with the assessment of other risk factors, is the basis for the use of more complex special methods for diagnosing fetal abnormalities.

Limits of detection: 0.03 mU/ml-100 mU/ml

PAPP-A (blood level determination)

What is it for

PAPP - A (Pregnancy-associated Plasma Protein-A)

Pregnancy-associated plasma protein-A ( PAPP - A ) was first described in 1974 as a high-molecular-weight protein fraction in the blood serum of women in late pregnancy.
It turned out to be a large zinc-containing metaloglycoprotein with a molecular weight of about 800 kDa. During pregnancy, plasma protein is produced by syncytiotrophoblast (tissue that is the outer layer of the placenta) and extravillous cytotrophoblast (islands of fetal cells in the thickness of the uterine mucosa) and enters the mother's bloodstream. The biological significance of this protein is not fully understood. It has been shown to bind heparin and is an inhibitor of granulocyte elastase (an enzyme induced by inflammation), so it is assumed that pappa modulates the maternal immune response and is one of the factors that ensures the development and survival of the placenta. In addition, it was found to be a protease that cleaves insulin-like growth factor binding protein 4. There are serious reasons to believe that plasma protein is one of the factors of paracrine regulation not only in the placenta, but also in some other tissues, in particular in atherosclerotic plaques. It is proposed to use this marker as one of the risk factors for coronary heart disease.

Concentrations of plasma protein in maternal blood continually increase with increasing gestational age. The greatest increase in this indicator is observed at the end of pregnancy.

Over the past 15 years, PAPP-A has been studied as one of three risk markers for trisomy 21 (Down syndrome) (along with free hCG beta subunit and nuchal translucency thickness). It turned out that the level of this marker at the end of the first trimester of pregnancy (8-14 weeks) is significantly reduced if the fetus has trisomy 21 or trisomy 18 (Edwards syndrome). The uniqueness of this indicator is that its significance as a marker of Down syndrome disappears after 14 weeks of pregnancy. In the second trimester, its levels in maternal blood in the presence of trisomy 21 in the fetus do not differ from those in pregnant women with a healthy fetus. If we consider PAPP-A as an isolated risk marker for Down syndrome in the first trimester of pregnancy, its determination at 8-9 weeks would be most significant. However, the free beta subunit of hCG is a stable marker of the risk of Down syndrome in the period of 10-18 weeks, i.e., later than PAP - A. Therefore, the optimal period for donating blood for a double test in the first trimester of pregnancy is 10-12 weeks.

The combination of measuring the level of PAPP-A with determining the concentration of the free beta subunit of hCG in the blood and determining TVP using ultrasound at the end of the first trimester of pregnancy can identify up to 90% of women at risk of developing Down syndrome in the older age group (after 35 years). The probability of false positive results is about 5%.

In addition to prenatal screening for the risk of Down syndrome and Edwards syndrome, in obstetrics the PAPP-A determination is also used for the following types of pathology:

• Threat of miscarriage and stopping the development of pregnancy in the short term
• Cornelia de Lange syndrome.

Diagnosis of the risk of fetal growth arrest in early pregnancy was historically the first clinical application of determining PAPP-A in blood serum, proposed in the early 1980s. It has been shown that women with low levels of PAPP-A in early pregnancy are at risk for subsequent pregnancy loss and severe forms of late toxicosis. Therefore, it is recommended to determine this indicator at 7-8 weeks for women with a history of severe pregnancy complications.

Cornelia de Lange syndrome is a rare form of congenital malformation of the fetus, found in 1 in 40,000 births. The syndrome is characterized by mental and physical retardation, heart and limb defects, and characteristic facial features. It has been shown that in this condition, the level of the indicator in the blood at 20-35 weeks is significantly lower than normal. A study by Aitken's group in 1999 showed that this marker could be used to screen for Cornelia de Lange syndrome in the second trimester of pregnancy, since levels in such pregnant women were on average 5 times lower than normal.

The reagents used to determine PAP-A and the free beta subunit of hCG are an order of magnitude more expensive than the reagents used for most hormonal indicators, which makes this test a more expensive test compared to the determination of most hormones of the reproductive system.