RARR analysis

To prevent complications during pregnancy and to prevent genetic and congenital anomalies in the future child, pregnant women undergo perinatal screening - a special set of examinations. This set includes the determination of alpha-fetoprotein, human chorionic gonadotropin, free estriol, placental lactogen, inhibin A, as well as PAPP analysis and a number of other studies.

In this article we will talk about the analysis of PAPP-A – a plasma protein, the determination of which is of no small importance during pregnancy.

[ 1 ], [ 2 ], [ 3 ]

Indications for the PAPP test

• Perinatal screening, which is carried out to assess the risk of chromosomal abnormalities in the embryo at 9-13 weeks.
• Previously observed complicated pregnancy courses (spontaneous abortions, early fetal deaths).
• The pregnant woman is over 35 years old.
• History of hepatitis, herpes infection, cytomegalovirus, rubella during previous pregnancies.
• If the family already has a child with chromosomal abnormalities or developmental defects.
• Genetic pathologies in the parents, brothers and sisters of the pregnant woman.
• Exposure of one of the parents of the unborn child to radiation or other harmful exposures.

The analysis is usually done over 1-2 days. Blood is taken in the morning, on an empty stomach. The day before, you should not drink alcohol, eat sweets, overeat, or do heavy physical work.

What does PAPP-A mean?

PAPP-A is a special protein that begins to be produced in large quantities during pregnancy. Normally, everyone has a little of this protein, a high-molecular glycoprotein: it is produced in the blood serum. However, in pregnant women, it begins to be synthesized by the trophoblast, the outer cell layer of the embryo, with the help of which its implantation into the uterine wall occurs.

The plasma protein A (PAPP-A) test is prescribed in order to detect any abnormalities in the developing embryo in time, since ultrasound at this time cannot yet assess the formation and development of the fetus.

Experts are inclined to believe that changes in the amount of plasma protein A are often associated with the risk of developing Down's syndrome or other chromosomal abnormalities in the child. In addition, changes in the indicators may indicate a threat of spontaneous termination or cessation of pregnancy development. For this reason, the PAPP-A analysis is mandatory in the list of perinatal screening studies.

PAPP during pregnancy is considered informative starting from the 8th week of gestation, however, doctors often prescribe the PAPP test in combination with β-hCG, that is, from the 11th to the 14th week. It should be noted here that the results of the PAPP analysis, which was carried out later than the 14th week, can no longer be considered reliable, since from this period plasma protein A no longer serves as a marker of chromosomal abnormalities.

In order to state with some accuracy the risk of the fetus developing Down's syndrome and other anomalies, the doctor must consider not only the PAPP-A indicator directly, but also its relationship with the β-hCG result and ultrasound readings.

The time interval between the ultrasound and taking blood for biochemistry (PAPP and hCG) should not exceed 3 days, otherwise the readings may be inaccurate. Along with the PAPP readings, hCG is determined simultaneously.

Results of PAPP-A

PAPP-A decoding is carried out by a specialist who takes into account the ratio of data on the amount of plasma protein A, the β-hCG indicator, and the results of ultrasound screening. In addition, the body weight of the expectant mother, the facts of smoking of the pregnant woman, conception during IVF, taking certain medications, diabetes, as well as the presence of multiple pregnancies are necessarily taken into account.

There are different indicators of the PAPP norm by weeks of pregnancy. The PAPP-A table indicates data depending on the period:

Week of pregnancy	PAPP-A index, mIU/ml
From 8 to 9 weeks	0.17 – 1.54
From week 9 to week 10	0.32 – 2.42
From week 10 to week 11	0.46 – 3.73
From week 11 to week 12	0.79 – 4.76
From 12 to 13 weeks	1.03 – 6.01
From week 13 to week 14	1.47 – 8.54

If PAPP-A is below normal, this may indicate that the unborn child is at risk of the following diseases:

• Edwards disease is a disorder of chromosome 18 that combines multiple developmental anomalies of a constitutional and mental nature;
• Down's syndrome is an anomaly of the 21st pair of chromosomes, characterized by signs of delayed mental and physical development;
• Amsterdam dwarfism syndrome (Cornelia de Lange) is a disease of gene mutations that manifests itself as a delay in psychomotor development to varying degrees;
• other chromosomal abnormalities (Rubinstein-Taybi disease, mental retardation with hypertrichosis, etc.).

For a pregnant woman, a decrease in PAPP-A levels may indicate a threat of termination or a frozen pregnancy.

If PAPP-A is elevated, it is usually not a cause for concern: perhaps your gestational age has not been accurately determined, or the outer cell layer of the fetus is synthesizing more plasma protein than usual.

Do not forget that the PAPP-A test result is not considered separately from the β-hCG and ultrasound examination indicators. Chromosomal abnormalities in the fetus can be suspected only if there is a combination of significantly reduced PAPP-A, increased β-hCG and a characteristic indicator on ultrasound, when the thickness of the nuchal translucency in the fetus is more than 3 mm.

Moreover, the PAPP-A test result does not establish a 100% diagnosis. It only makes it possible to determine the existence of a risk of chromosomal abnormalities, which determines the need for more careful monitoring of the course of a given pregnancy.

MoM PARR-A – what is it?

In order to determine the degree of risk of chromosomal abnormalities, specialists use not so much the PAPP-A indicators directly, but rather the MoM calculation.

MoM serves as a coefficient indicating the level of deviation of the perinatal screening indicator from the average indicator for a particular week of pregnancy.

How to calculate MoM?

To do this, it is necessary to divide the PAPP-A indicator by the average value corresponding to the week of pregnancy.

The MoM PAPP-A norm is considered to be an indicator close to one, but can fluctuate within the range of 0.5 – 2.5, and in case of multiple pregnancies – up to 3.5 MoM.

There is no need to worry ahead of time: the results obtained only indicate whether the pregnant woman falls into the risk group for the possibility of developing chromosomal abnormalities. If such a risk exists, the course of pregnancy will be monitored especially closely, conducting the necessary examinations and tests.

Of course, only you have the right to decide whether to take a particular test. After all, even having discovered chromosomal abnormalities in the fetus, medicine cannot cure or correct them. Confirmation of the degree of risk only gives the expectant mother the opportunity to decide: to continue the pregnancy and be ready for anything, or to terminate it. Of course, in some cases the tests may be false positive, but unfortunately, no one can guarantee the result.

Advice: Whether you agree to take the PAPP test or not, consult with a good genetic specialist who will determine the need for further additional testing for you.