Pappa analysis. Why do you get tested for RRR and hCG?

This is a protein that is produced in large quantities during pregnancy. Its level is used to assess the risk of chromosomal abnormalities in the prenatal diagnosis of fetal pathologies.

SynonymsEnglish

Pregnancy-associated plasma protein-A (PAPP-A), pappalysin 1.

Research method

Solid-phase chemiluminescent enzyme-linked immunosorbent assay (“sandwich” method).

Units

MMU/ml (milli-international unit per milliliter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

Avoid fatty foods from your diet for 24 hours before donating blood.
Avoid physical and emotional stress and do not smoke 30 minutes before the test.

General information about the study

Pregnancy-associated plasma protein-A (PAPP-A) is a zinc-containing enzyme (metalloproteinase). During pregnancy, it is produced in large quantities by fibroblasts in the outer layer of the placenta and decidua and is found in the maternal bloodstream as a high molecular weight protein fraction.

The PAPP-A enzyme cleaves protein fragments from insulin-like growth factor and increases its biological activity, thereby ensuring the 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 maternal body. Its content in the blood increases with the progression of pregnancy. It does not significantly depend on parameters such as the sex 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 childbirth, PAPP-A declines rapidly over several days.

With a chromosomal abnormality with fetal malformations, the concentration of PAPP-A in the blood decreases significantly from the 8th to the 14th week of pregnancy. The most dramatic 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 in the norm. The level of PAPP-A in the mother's blood serum drops even more sharply if the fetus has a genetic pathology with multiple malformations - Cornelia de Lange syndrome.

The test is prescribed in combination with the determination of the beta subunit of human chorionic gonadotropin and an ultrasound examination of the thickness of the nuchal translucency. This comprehensive examination is recommended for screening for Down syndrome and other chromosomal abnormalities of the fetus in the first trimester of pregnancy (10-13 weeks). A separate determination of PAPP-A is most informative at 8-9 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.

Based on the results of this test, a decision is made on the advisability of prescribing additional methods of examining the fetus. However, the PAPP-A level cannot serve as a criterion for diagnosis. In normal pregnancies, the test result can be false positive in 5%, and fetal chromosomal abnormalities are detected in only 2-3% of pregnant women with reduced PAPP-A levels. In the United States, using 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 necessary, including chorionic villus puncture, amniocentesis with genetic testing of the material obtained.

PAPP-A protein can be found in minimal amounts in men and non-pregnant women. An increase in PAPP-A is recorded after damage to atherosclerotic plaques in acute coronary syndrome and unstable angina. This protein is being actively studied as a marker for the prognosis of coronary heart disease, but has not yet received widespread use in cardiac laboratory tests.

What is the research used for?

To screen for possible chromosomal abnormalities in the fetus.
To assess the threat of premature termination of pregnancy or miscarriage, to predict the course of pregnancy.

When is the study scheduled?

When examining pregnant women in the first trimester (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 complications of pregnancy in the past;
chromosomal pathologies, Down's disease or congenital malformations in previous pregnancies;
hereditary diseases in the family;
past infections, radiation exposure, taking medications in the early stages of pregnancy or shortly before it that have a teratogenic effect (can cause congenital defects and fetal anomalies).

What do the results mean?

Reference values

Causes of increased levels of pregnancy-associated plasma protein-A (PAPP-A):

multiple pregnancy,
large fetus and increased placental mass,
low location of the placenta.

Causes of decreased levels of pregnancy-associated plasma protein-A (PAPP-A):

Down syndrome - trisomy on chromosome 21 (mental retardation, congenital heart disease, characteristic facial features and other anomalies);
Edwards syndrome - trisomy on chromosome 18 (profound mental retardation, heart defects, structural anomalies of the skull, low position of the ears, foot dysplasia and other anomalies);
Patau syndrome - trisomy on the 13th chromosome (cleft lip and palate, polydactyly - extra fingers or toes, underdevelopment of the external genitalia, microcephaly - reduced size of the skull and brain, microphthalmia - underdevelopment of the eye, and other anomalies);
Cornelia de Lange syndrome is a genetic disease with multiple congenital defects (growth and development delay, mental retardation, microcephaly, visual impairment, cleft palate and other anomalies);
threat of miscarriage and early termination of pregnancy;
fetoplacental insufficiency;
fetal malnutrition (insufficient weight due to malnutrition).

What can influence the result?

Destruction of red blood cells in the sample and violations of blood collection technique can distort the result.
During multiple pregnancy, the content of PAPP-A in the mother's blood increases and it is difficult to assess the likelihood of chromosomal abnormalities.
If the gestational age of the fetus is incorrectly determined, the result may be falsely increased or decreased.

Important Notes

The test for pregnancy-associated plasma protein-A in pregnant women is not used to diagnose fetal pathology and placental insufficiency, but to assess their likelihood. Making a decision to terminate a pregnancy based on changes in PAPP-A levels would be a grave mistake.
The use of invasive diagnostic methods (chorionic villus biopsy, amniocentesis, cordocentesis) is not recommended if screening tests are normal and there are no changes on ultrasound.

Placental lactogen

Who orders the study?

Obstetrician-gynecologist, medical geneticist.

Literature

Gorin V. S., Serov V. N. and others . Pregnancy-associated protein A and other macroglobulins as protein markers of perinatal pathology. Russian Bulletin of Perinatology and Pediatrics, N 4, 1998, pp. 18-24.
Body R., Ferguson C. Pregnancy? associated plasma protein A: a novel cardiac marker with promise. Emerg Med J. 2006 November; 23(11): 875–877. PMCID: PMC2464389.
Brügger-Andersen T, Bostad L, and others. The activity of pregnancy-associated plasma protein A (PAPP-A) as expressed by immunohistochemistry in atherothrombotic plaques obtained by aspiration thrombectomy in patients presenting with a ST-elevation myocardial infarction: a brief communication. Thromb J 2010 Jan 27;8(1):1. PMID: 20181026.

In order to prevent any pregnancy complications and prevent various fetal abnormalities, pregnant women must undergo a whole range of different examinations. This complex includes the PAPP analysis, which is carried out together with other studies.

What is PAPP-A

PAPP-A is a plasma protein that only pregnant women can produce. Naturally, it is present in small quantities in the blood serum of every person. But the outer cellular layer of the embryo begins to synthesize this substance in large volumes.

Analysis of this protein (PAPP-A) makes it possible to identify whether there are any disturbances in the development of the embryo. Because ultrasound in early pregnancy does not show the necessary information about the condition of the fetus.

Doctors say that if the amount of plasma protein in the blood changes, this may indicate that the unborn child is developing some kind of disease associated with the set of chromosomes, for example, Down syndrome. Fluctuations in the level of plasma protein-A in the blood may also indicate a risk of miscarriage or spontaneous abortion. PAPP analysis, precisely because of the enormous significance of changes in its quantity for diagnosing fetal development, is one of the most important in perinatal screening studies.

PAPP analysis provides useful information as early as 8 weeks of pregnancy. Doctors generally prescribe this test along with HCG, which requires a blood sample. These studies are carried out between 11 and 14 weeks. If this analysis is done later, it will not provide reliable information.

To be completely sure whether or not some chromosomal disease is developing in the fetus, the doctor must conduct a set of tests: PAPP, hCG and ultrasound. Between the time when the ultrasound was performed and the time when blood was taken for biochemistry, no more than three days should pass. Otherwise, the research will not give such accurate results.

In what cases is it necessary to carry out the PAPP-A test?

Blood for a test for the amount of plasma protein-A is donated in the following cases:

The analysis takes no more than two days. Blood for research is taken in the morning, provided that the woman does not eat anything. The day before, a pregnant woman should not drink alcohol, sweets, or simply overeat. It is also not recommended to engage in heavy labor.

What do the results of PAPP-A mean?

Decoding of PAPP is carried out taking into account the amount of plasma protein, hCG indicator and ultrasound results. In this case, attention should be paid to the body weight of the pregnant woman, her attitude towards bad habits, conception as a result of IVF, as well as the presence of diabetes mellitus and medication use.

The PAPP norm is different for each week of pregnancy. It grows from 8 to 14 weeks. Initially, this norm becomes 0.17 honey/ml, and at the end - 8.54 honey/ml.

If PAPP-A levels are lower than they should be normal, this may indicate that the fetus may develop one of the following diseases:

Edwards disease is a disorder on chromosome 18 that results in abnormal development of both physical and mental development.
Down's disease is a disorder in chromosome 21, which entails a delay in the development of the psyche and physical characteristics.
Cornelia de Lange syndrome is a gene mutation that subsequently delays the child’s development of psychomotor skills.
Other diseases associated with chromosomes.

Pregnant women who have abnormal PAPP levels are at risk of fetal failure or miscarriage.

If the PAPP level is high, this may mean that you have been diagnosed with the wrong gestational age. Another reason for this may be that the fetus synthesizes more protein than it should.

Do not forget that in order to begin to suspect that the fetus has abnormalities at the chromosomal level, it is necessary to conduct a series of studies. Only if the level of PAPP-A is much lower than normal, hCG is elevated, and an ultrasound showed the thickness of the nuchal space in the fetus is greater than 3 mm, can we speak with certainty about abnormalities in the development of pregnancy.

Unfortunately, the PAPP analysis and its result do not diagnose the disease for sure. It just helps determine that there is a risk of a chromosomal disorder in the fetus. This means that a pregnant woman must undergo a thorough examination and be under constant medical supervision throughout her pregnancy.

In any case, you should not give in to panic ahead of time. The analysis only tells whether a pregnant woman is at risk or not.

While waiting for the baby, the expectant mother undergoes many tests and also undergoes various examinations. The main purpose of such monitoring is to control the development of the baby and the course of pregnancy. One of the routine examinations is the first prenatal screening (first trimester screening) - a comprehensive examination that includes an ultrasound and blood tests for certain parameters. The obtained biochemistry data allows us to assess the risks of chromosomal abnormalities in the child, as well as the prognosis of pregnancy (threat of termination or miscarriage). What is a double test? What tests are included in it?

Biochemical screening of the first trimester has another name - a double test. The blood test takes place on the same day as the ultrasound. It is advisable to conduct the examination in the period from 8 to 14 weeks. However, due to the fact that the assessment of the results obtained is carried out in conjunction with ultrasound data, women take a double test in the interval from 11 to 13 weeks of gestation. The test is taken on an empty stomach. Moreover, in order not to distort the real picture, on the eve of blood sampling it is recommended to adhere to a diet - exclude fatty, fried, smoked and spicy foods, sweets, chocolate, meat and seafood.

Biochemical screening is not a mandatory test. This examination is recommended for women at high risk:

Age exceeds 35 years (since the older the pregnant woman, the higher the risk of chromosomal abnormalities in the baby).
Children with genetic disorders have already been born before.
While waiting for the baby, infectious diseases were identified or suffered.
There are genetic disorders in close relatives.
Harmful working conditions (especially if the work involves a risk of exposure to radiation).
There is a history of miscarriage (or miscarriages).

The study includes checking the venous blood of the expectant mother for the content of PAPP and hCG. What do these abbreviations hide?

PAPP-A indicator during pregnancy

PAPP is a protein produced in blood plasma. Active synthesis of this substance begins from the moment the embryo implants into the wall of the uterus - the protein is produced by the outer cellular layer of the embryo and is responsible for the growth of the baby’s tissues. It is for this reason that the indicator of this marker plays an important role in diagnosing the normal development of a child. Even in the early stages of pregnancy, when ultrasound monitoring does not yet make it possible to discern a possible problem, the value of the PAPP-A protein can already signal about it. With increasing gestational age, the concentration of this protein in the blood also increases, however, after the 14th week of pregnancy, the level of plasma protein A may be within normal limits, even in the presence of pathology. For this reason, the optimal study period is the first trimester. Since the PAPP-A test is taken in conjunction with an ultrasound scan during pregnancy, the study is most often carried out at 12 weeks. This period is also a limit from the point of view of perinatal gradation - from this moment the embryo is called a fetus. The main purpose of the analysis for PAPP-A is to determine whether the protein content in the blood is normal, since this index is the main marker of chromosomal pathologies.

Free β-hCG unit during pregnancy

β-hCG - human chorionic gonadotropin - a hormone synthesized by the membrane (chorion) of the fetus. It is the increase in the content of this hormone, found in the blood and urine of a woman, that allows us to talk about the onset of pregnancy in the earliest stages. The level of this hormone continuously increases in the first weeks, reaching its peak at 12-13 weeks of gestation. Further, the hCG level decreases slightly and remains at the same level throughout pregnancy. During the first prenatal screening, the content of this hormone in the blood of the expectant mother is also assessed.

Calculation of risks of chromosomal diseases

In addition to conducting the actual blood test for the content of the hormone hCG and plasma protein A associated with pregnancy, based on all the entered data, the program makes an additional calculation of the individual risks of genetic pathologies in the child - Down, Edwards and Patau syndrome. The result is given as a ratio of 1:XXX, i.e. 1 out of XXX women gives birth to a child with the specified anomaly. Accordingly, the lower the XXX value, the higher the likelihood of having a developmental defect. Threshold values for each syndrome are indicated next to the pregnant woman's data. Do not forget that these values only indicate a greater or lesser probability of deviation, but do not indicate its mandatory presence.

An increase in β-hCG during pregnancy is possible with:

Down syndrome.
Pregnancy with two or more babies.
Diabetes mellitus in pregnancy.
In case of severe toxicosis.
Hydatidiform drift.

β-hCG during pregnancy below normal is possible with:

Edwards syndrome.
High risk of miscarriage or fading of pregnancy.
Placental insufficiency.
Ectopic pregnancy - in this case, the pathology is usually detected at an earlier stage.

PAPP-A level during pregnancy

A prenatal screening blood test shows the levels of pregnancy-associated plasma protein A, PAPP-A. The compliance of this indicator with the norm is determined by such a characteristic as MoM. This coefficient shows compliance with the average value (median) for the current stage of pregnancy. MoM is calculated as the quotient between the obtained data on pregnancy-associated plasma protein and the median value for a given gestational age. A deviation from MoM in the direction of decrease or increase indicates, respectively, low or high PAPP-A during pregnancy. When assessing biochemistry data, the specialist does not study the indicator of pregnancy-associated protein (PAPP-A) separately, but considers it in conjunction with hCG data or an ultrasound picture.

PAPP-A is reduced during pregnancy

A decrease in the concentration of protein A, which is associated with pregnancy, PAPP, is an unfavorable sign. This picture is possible with:

Threat of spontaneous miscarriage or fading of pregnancy.
Down syndrome (trisomy 21).
Edwards syndrome (trisomy 18) - there is a significant decrease in PAPP-A.
Cornelia de Lange syndrome.

Elevated PAPP-A during pregnancy

An isolated increase in this value has no diagnostic value. This test result may be a consequence of low placental attachment, multiple pregnancy, or an incorrectly indicated gestational age. If a pregnant woman is overweight (obese), the value of plasma protein may also be increased. The likelihood of chromosomal abnormalities with elevated PAPP-A is low, although it cannot be completely excluded. Elevated plasma protein levels are assessed in conjunction with β-hCG data.

PAPP test during pregnancy

When assessing the results obtained, not only the data of other examinations and analyzes are taken into account, but also the age of the expectant mother, as well as her body weight. Since plasma protein concentration constantly increases in the first weeks, when performing a PAPP-A blood test during pregnancy, it is important to correctly and accurately indicate the gestational age. Inaccuracy in this parameter can significantly distort the results. Plasma protein A content is determined in mU/ml.

PAPP-A during pregnancy is normal

Depending on the period of gestation of the toddler, protein standards also differ:

for 10-11 weeks - 0.45-3.73 mU/ml;
for weeks 11-12 - 0.78-4.77 mU/ml;
for weeks 12-13 - 1.03-6.02 mU/ml;
for weeks 13-14 - 1.47-8.55 mU/ml.

The obtained data from the analysis of PAPP-A during pregnancy are interpreted not only in accordance with the normal criteria, but also with the MoM value. An acceptable median value is in the range from 0.5 to 2 MoM. If we are talking about multiple pregnancies, the upper limit is moved to 3.5 MoM.

PAPP-A during pregnancy - deviation from the norm

If the obtained data falls outside the specified intervals, it is assessed as a deviation from the norm. If the results of the PAPP-A analysis during pregnancy reveal discrepancies with the reference intervals, the woman is recommended to consult a geneticist, as well as conduct additional examinations. The most informative from the point of view of excluding or confirming chromosomal diseases of the baby are: chorionic villus biopsy, amniocentesis - puncture of the fetal membrane to collect the amniotic fluid of the baby, or cordocentesis - collection of umbilical cord blood. The results of all procedures have a high reliability of 98-99%. Despite the informative nature of the studies, they are not popular due to their invasiveness. Many women are afraid of the risks associated with these manipulations. Even if the screening results (ultrasound data and biochemistry indicators) indicate a high risk of pathologies, the woman has the right to refuse additional examinations.

When a long-awaited pregnancy occurs, a woman tries with all her might to make it as successful as possible. Medical diagnostics today are an excellent way to detect developmental defects and prevent their consequences without harming the mother and child.

Today there are no expectant mothers who do not undergo the first prenatal screening. This is a comprehensive study that can identify pathologies and abnormalities of fetal development in the early stages. This also includes an analysis for plasma protein PPAP. Every expectant mother should know about the PAPP-A norm during pregnancy. This indicator plays an important role in diagnosing one or another form of developmental disorder in the future baby.

Why is screening done?

A pregnant woman is wary of any examination prescribed by a doctor. After all, the main thing now is that nothing threatens the baby. Therefore, when a gynecologist gives a referral for screening at 13 weeks 6 days, the expectant mother often does not know what to expect from all this and is very worried.

In fact, prenatal examination is as safe as possible and is prescribed to absolutely everyone at 11–13 obstetric weeks due to the simple methods of its implementation:

ultrasonography;
screening biochemical blood test.

The first prenatal screening is prescribed at 11 - 13 weeks 6 days. It is during this period that this survey is most informative.

It is especially important for a woman with a complicated pregnancy or previous unsuccessful attempts to carry a baby to undergo the study. These risk factors include:

a woman whose age is 35+;
the presence of previous pregnancies that ended in spontaneous miscarriages or non-developing pregnancy;
there is already a child growing up in the family with a chromosomal or genetic pathology;
during real pregnancy in the early stages up to 13 weeks, a serious infectious disease was suffered;
the influence of harmful factors associated with a woman’s profession;
the expectant mother's addiction to alcohol and drugs.

An ultrasound examination is performed first, and then on the same day blood is donated for biochemical screening. Compliance with this sequence together guarantees a reliable research result. The first screening requires the most correct gestational age, down to the day. Only an ultrasound diagnostic doctor can determine the exact period. In addition, only an ultrasound will give a result about whether the pregnancy is singleton or multiple. Without this information, it is generally not advisable to donate blood, since you will not get high-quality results.

Biochemical blood test for screening in the 1st trimester

At the time of donating blood, the expectant mother should already have ultrasound results in her hands with the exact gestational age and accompanying comments from the doctor. For example, if ultrasound diagnostics revealed fetal freezing, then further analysis is simply pointless.

Donating blood for such an examination involves a number of rules:

To be taken exclusively on an empty stomach. Water is allowed only if the mother has severe toxicosis or dizziness.
If possible, donate blood as early as possible, but without confusing the sequence of procedures. If the process of donating biomaterial takes a long time, take a snack with you and eat immediately after leaving the treatment room.
A couple of days before the scheduled test, exclude a number of foods from your diet: fatty and smoked foods, nuts, chocolate, seafood.
The day before donating the biomaterial, heavy physical activity should be avoided.

A blood biochemistry test is aimed at studying two indicators:

free human chorionic hormone (hCG);
plasma protein PAPP-A.

The results of biochemical screening are ready within 2 days.

What is PAPP-A

PAPP-A is a plasma protein that the body begins to actively secrete during pregnancy.

It is produced by the outer layer of the embryo at the moment when it penetrates the walls of the uterus. That is why a blood test for the level of this protein is of utmost importance for the early diagnosis of abnormal development of the unborn baby. Even at the very beginning of pregnancy, when ultrasound is unable to detect a problem, PAPP-A indicators can signal its presence.

A change in the quantitative deviation from the PAPP norm may indicate:

Down syndrome;
frozen pregnancy;
risk of miscarriage.

A blood test for PAPP-A must be taken before the 14th week of pregnancy. At a later date, you should not expect reliable results. After 14 weeks, the PAPP-A indicator in a woman with a genetic-chromosomal pathology of the fetus will be exactly the same as in a woman carrying a healthy baby.

Any deviation from the norm during pregnancy, be it an increase or decrease in plasma protein levels, should be a cause for concern.

IMPORTANT! Only a combination of ultrasound and biochemical screening results can give a complete picture of the course of pregnancy. Blood should be donated no later than 3 days after the ultrasound examination. The doctor does not give you an exact diagnosis, but only points out possible pathologies that can be confirmed or refuted using more accurate examination methods.

Blood test results for PAPP-A

When interpreting the results of the first screening, the gynecologist takes into account all the characteristics of the pregnant woman: weight, the presence of diabetes, whether any medications were taken at the time of the test, the presence or absence of bad habits, whether the pregnancy was achieved through IVF or not, and many others.

Plasma protein levels increase from 8 to 13-14 weeks.

Normally, a pregnant woman's PAPP-A level varies depending on the week of pregnancy.

Deviations from the norm may indicate a genetic-chromosomal pathology on the part of the fetus, and a pregnant woman is at risk for fetal failure or spontaneous miscarriage.

Pregnancy-associated PAPP-A protein may be elevated for a number of other reasons:

the child’s weight is quite large;
low location of the placenta;
multiple pregnancy.

Results of the analysis in MoM

When the results of blood screening reach the doctor leading the pregnancy, he converts the indicators in units into the MoM coefficient. It reveals the percentage of deviations in a particular woman from the average norm.

If the screening result is positive, the MoM coefficient varies from 0.5 to 2.5.

In all laboratories, the MoM coefficient standards are the same. Therefore, to retake the analysis, you can choose absolutely any institution if you do not trust the results of your own.

PAPP-A norms for multiple pregnancies

Already at thirteen weeks, during 1 screening, the doctor can detect two or more embryos in the uterine cavity. Multiple pregnancy is a complicated pregnancy and requires special monitoring throughout the entire period of pregnancy. The risk of such a pregnancy may be that one fetus develops without visible pathologies, and the second has signs of developmental abnormalities already at 13 weeks. Therefore, it is very important for the expectant mother to seriously approach the issue of first prenatal screening.

At the first screening during a twin pregnancy, the test norms will be slightly different than during a singleton pregnancy.

Firstly, the main study will be an ultrasound, where the doctor will pay special attention to the collar area of the baby. This is where fluid accumulates, signaling possible Down syndrome.

Secondly, the doctor will not prescribe a biochemical blood screening. In the case of a multiple pregnancy, it will be uninformative and can give both falsely increased and falsely decreased results. It is possible that the mother’s blood can only be used to determine the MoM coefficient. Normally, in a pregnant woman with twins, it reaches 3.5 MoM.