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    fertility basics

    PAPP-A Test - Role, Purpose, Uses and Test Results

    • 4.5   (1 Votes)

    Pregnancy-associated plasma protein-A (PAPP-A) test is performed between 11 and 14 weeks of a pregnancy to check for any chromosomal defect in the fetus. First trimester blood test PAPP-A is done for defects like trisomy 18, and trisomy 21 (Down's Syndrome). Papp-A test normal range is from 0.5 MOM to more than that value.

    Pregnancy is an overwhelming experience in the life of a woman. A pregnant woman needs to undergo certain medical screening tests for a healthy pregnancy which can lead to successful delivery. First-trimester screening is a combination of fetal ultrasound and maternal blood testing performed during the early phases of pregnancy. This screening process is performed to help to determine the possibilities of risk associated with the fetus having certain birth defects. Great progress has been observed in understanding the function of PAPP-A gene along with its tests in pregnancy. In the year 1974, PAPP-A test was among four proteins identified in the plasma of a pregnant woman, and, accordingly, given the title ‘pregnancy-associated plasma protein-A’.(1)

    This article contains detailed information about:

    Before discussing several aspects of PAPP-A blood test, its purpose and risks, it is important to have a complete understanding of the role of prenatal screening in pregnancy.

    1. Role of Prenatal Screening:

    Pregnancy care comprises regular appointments with the fertility doctor or midwife in order to monitor the pregnancy and the baby’s growth. Care includes certain screening tests which are performed to check on the health of both the mother and the baby, and help to identify any complications with pregnancy. The screening tests which are performed during pregnancy are termed as a ‘prenatal screening’. Tests for certain specific medical conditions (neural tube defects like spina bifida, or other genetic conditions known to be present in a family) are performed in prenatal screening for pregnancy. A woman may or may not want to proceed with these tests, and may like to discuss her options with her specialists or with a genetic counselor before making a decision.

    Role of Prenatal Screening

    The purpose of the prenatal screening is to check for the possibilities or chances of chromosomal defects such as Down’s Syndrome, Edwards’ Syndrome, and Patau’s syndrome. Screening for Down's syndrome is performed to inform women who wish to have this information as early as possible so that they can make a well-guided decision about further solutions to pursue a healthy pregnancy. These medical tests can prove to be helpful in providing an estimate of how likely it is that a baby is affected by a range of medical conditions but cannot make a diagnosis. The combined first-trimester screening test is a blend of effective information from a first-trimester ultrasound and a blood test from the mother (first-trimester maternal serum screening). The screening test is conducted with a purpose to calculate the possibility of risks for a group of chromosomal disorders, including Down's Syndrome. The blood test comprises an easy blood test between 9 and 14 weeks and an ultrasound scan between 11 and 14 weeks of pregnancy.

    2. What is a PAPP-A blood test?

    PAPP-A is a typical biomarker for screening of chromosomal abnormality like Down's Syndrome in pregnant women. (2) Pregnancy-associated plasma protein-A (PAPP-A) is a hormone which is made by the placenta (afterbirth) in pregnancy. It is measured as part of the combined screening blood test and an ultrasound. Pregnancy-associated Plasma Protein-A (PAPP-A) is an insulin-like growth factor binding protein metalloproteinase complex which is predominantly produced by the placenta in the woman. It has been implicated in the paracrine and autocrine control of trophoblast invasion of the decidua. PAPP-A blood test is used as a vital predictor of certain obstetrics outcome.(3)Pregnancy-associated Plasma Protein-A (PAPP-A) is the largest of pregnancy-associated proteins produced by both embryo and placenta (syncytial cytotrophoblasts) during pregnancy. This protein is thought to have various different functions, including preventing matrix mineralization, recognition of the fetus by the maternal immune system, and angiogenesis. PAPP-A levels tend to rise from first screening in the first trimester until a successful pregnancy delivery in the respective case.(4)Detection of PAPP-A is also recommended as a first and second-trimester diagnostic test for aneuploidies, including chromosomal disorder like Down's Syndrome or Trisomy 21. Maternal serum concentrations are linked with subsequent fetal growth which has suggested that it can be used as a diagnostic examination for adverse pregnancy results (preeclampsia, intrauterine growth restriction, stillbirth, and premature birth).

    Another name for PAPP-A Test:

    Pregnancy-associated plasma protein-A (PAPP-A) with hCG, total, or free beta subunit and nuchal translucency ultrasound.

    3. Purpose of PAPP-A test:

    The purpose of PAPP-A test is to assess the risk of the baby having a chromosomal abnormality, such as Down syndrome (Trisomy 21) or Edwards’s Syndrome (Trisomy 18). In babies who are at an increased risk of having a chromosomal abnormality, there are chances that increased fluid would be present in the nuchal translucency. In such cases, often abnormally low or high PAPP-A or hCG levels are found in the resultant tests. The first-trimester screening combines the results from three measurements namely hCG, nuchal translucency, and PAPP-A. This screening is performed by carefully considering maternal age risk factors and ascertains an overall risk factor for a chromosomal defect.

    4. Uses of PAPP-A Test:

    The first-trimester screening is an impactful combination of tests such as PAPP-A, hCG, and nuchal translucency. These tests are used to assess the risk that the fetus a pregnant woman is carrying has a chromosomal disorder like Down's syndrome (Trisomy 21) or Edwards’s syndrome (Trisomy 18). The first-trimester screening is one of the most significant options a pregnant woman may be offered for prenatal Down syndrome screening. Other productive screening options include second trimester cell-free fetal DNA test and maternal serum screening. This test is beneficial as it gives the pregnant woman an option of earlier screening to check and find out the presence of any genetic disorders. PAPP-A, however, does not help in assessing the risk of neural tube defects like spina bifida. Neural tube defects are usually assessed in the second trimester of pregnancy. The screening is first performed at an advanced hospital when she first seeks prenatal care. This test is generally recommended by the healthcare practitioner between 11 and 14 weeks of pregnancy.(5)

    Uses of PAPP-A Test

    5. When PAPP-A Test is suggested?

    PAPP-A test is usually performed in the time period between 11 and 14 weeks of pregnancy.

    6. What happens in a PAPP-A blood test?

    The first-trimester screening in pregnancy is a combination of two blood tests and a special ultrasound imaging that are used to assess a pregnant woman's risk and complications of having a baby with Down syndrome (Trisomy 21) or Edward’s syndrome (Trisomy 18). Performing and evaluating the blood test and ultrasound together, plus considering the woman's age, increases both the specificity and sensitivity of the test results in the first trimester of pregnancy. Pregnancy-associated Plasma Protein A (PAPP-A) is a protein produced first by the growing placenta. The term came into successful existence by the PAPP-A gene in the human body. PAPP-A protein is a secreted protease whose main substrate is insulin-like that of growth factor binding proteins. Pappalysin-1 is also used in screening tests for chromosomal abnormality like Down syndrome. During a normal pregnancy, levels of pregnancy-associated plasma protein increase in the pregnant woman's blood at a certain place until delivery of the baby.

    Human Chorionic Gonadotropin (hCG) is a hormone produced during pregnancy in large quantities by the placenta. Total hCG or free beta subunit can be used in the first-trimester screening of pregnancy. Levels of both the hormones usually rise rapidly in the expectant mother's blood for the first 8 to 10 weeks, then decrease and stabilize at a lower level for the remainder time period of pregnancy. Nuchal translucency which is a common prenatal screening, performed with the assistance of ultrasound. The ultrasonographer performing the ultrasound measures the fluid collection between the spine and skin at the nape of the fetus's neck. It is a medical procedure that must be conducted by a highly-experienced radiologist who has a practice of performing the procedure. The purpose of this procedure is to make sure that the fetus is properly aligned and has been measured carefully. It is not a routine ultrasound, and this procedure is not availed at each and every health care facility or hospital. Sometimes, there are certain intensive complications depicted in the test results of the first-trimester screening. In such situations, the most impactful diagnostic tests like amniocentesis or Chorionic Villus Sampling (CVS) are suggested.

    7. How is PAPP-A test done?

    The first-trimester test involves 2 measurements:

    A sample of expectant mother’s blood is taken at a pathology collection centre between 9 weeks to 13 weeks 6 days of her pregnancy, but ideally between 9 to 12 weeks. The test is performed to check the levels of 2 hormones in the blood that change during pregnancy (free B-hCG and PAPP-A). Changes in these levels may indicate an aggravated chromosomal condition. An ultrasound scanning is conducted between 11 weeks to 13 weeks 6 days of pregnancy, ideally at 12 to 13 weeks to obtain the most accurate results. The ultrasound allows the thickness of fluid in an area behind the baby’s neck to be measured and determined. This area is known as 'nuchal translucency'. Nuchal Translucency is often larger in babies who are at risk of Down Syndrome. The person performing the ultrasound will also take some measurements to calculate the expectant mothers developing baby’s gestational age (age in weeks and days). A computer program is then used to combine these test results plus the woman’s exact age, weight and her baby’s correct gestational age, to identify the risk of the baby having Down syndrome, Trisomy 13, and Trisomy 18. The results are usually available within a week after the test is performed. The tests will be given to the fertility specialist who will inform the woman whether a physical abnormality has been found during the ultrasound examination.(6)

    8. PAPP-A Test Results:

    A genetic specialist interprets the screening results associated with the PAPP-A test performed. A mathematical calculation using the PAPP-A, hCG, and nuchal translucency ultrasound results obtained is used to tell a numeric risk of a chromosomal defect in the fetus. This risk is compared with an established cut-off related to the medical test. When the potential risk is higher in reference to the cut-off value, (e.g., probability of 1 in 230 or higher), then it is considered a positive screening. This may mean that the expectant mother is at an elevated risk for having a baby with a chromosomal disorder. Such cases need to be dealt in a proper manner. It is an important point to keep in mind that positive results in these fetal screening tests do not equate to the presence of fetal abnormalities in the fetus. They rather indicate further testing for obtaining optimum results. They indicate an increased risk of possible chromosomal defects. It has also been observed that a lesser percentage of women with a positive first-trimester screening showed babies with a chromosomal abnormality. In pregnancies carrying a chromosomal defect, such as the extra chromosome resulting in Down syndrome or Edwards syndrome, the levels of PAPP-A tend to be decreased.

    PAPP-A Test Results

    In such cases, the levels of hCG are significantly increased, and the space at the fetus's neck is usually larger than normal. While the first-trimester screen can accurately identify approximately 85 percent of women carrying a fetus with Down syndrome and up to 75 percent of those with Edwards syndrome, around 5 percent to 10 percent of normal pregnancies are expected to have a false-positive result. Even if a screening test is positive, certain other medical tests are required to determine and confirm a specific type of diagnosis. These may include a diagnostic test like Chorionic Villus Sampling (CVS) in the first trimester or amniocentesis in the second trimester. While these two procedures are more reliable than screening tests, they are also invasive and carry a mild risk of miscarriage and a rare risk of causing injury to the fetus. Despite this fact, screening does not detect all possible cases of fetal abnormalities which can occur in women.

    PAPP-A Test normal range:

    MoM value and concentration (IU/L) are the two parameters which are checked during the screening test of PAPP-A levels, around 12 weeks of pregnancy. MoM stands for a multiple of the median or average of all the tests. MoM value of 1.00 is average; more than 1.00 is above average and less than 1.00 is below average. PAPP-A levels higher or equal to 0.5 MoM is considered as normal and if the levels are lower than 0.5 MoM, they are considered to be low.

    PAPP-A Test Normal Range Chart:

    MoM (multiple of the median) Value

    PAPP-A Level: >=0.5 MoM=Normal

    PAPP-A Level: < 0.5 MoM=Low – studies have shown that these levels could lead to conditions like:

    • Preterm delivery
    • Small for gestational age (SGA)
    • Pre-eclampsia

    Several studies have revealed that pregnancy results of women with normal PAPP-A levels to be usually uneventful when compared to results of women with low PAPP-A level.

    Reliability of PAPP-Tests:

    These screening methods are effective. These tests are usually performed between 15-20 weeks. The blood screening primarily measures two hormones associated with pregnancy: PAPP-A and hCG.

    Potential Reasons for further screening tests:

    The first-trimester screening in pregnancy is a part of routine screening which is a non-invasive procedure. These screening usually do not pose any risks to the health of the mother and the baby. Performing further testing allows a doctor to confirm a diagnosis and then provides a woman with certain opportunities:

    • Pursue potential interventions that may exist (i.e. fetal surgery for spina bifida)
    • Start planning for a baby with special needs
    • Begin addressing anticipated lifestyle changes
    • Identify support groups and resources
    • Confirming about carrying the pregnancy to term

    Some women may elect not to pursue testing or additional testing for various reasons:

    • They are comfortable with the results regardless of the consequences of the chosen medical test
    • Owing to certain personal, moral, or religious reasons, making a decision about carrying the baby to term is not an option
    • Some couples decide not to allow any testing that poses any risk to the health of the developing baby

    It is important to discuss the risks and benefits of medical tests thoroughly with the healthcare provider to receive quality guidance. The healthcare provider will help patients evaluate if the benefits from the results could outweigh any risks from the treatment.

    9. Clinical Implications of low PAPP-A:

    A low PAPP-A level is a useful indicator of determining the risk of preterm delivery and a future chance of development of Pregnancy-induced Hypertension (PIH).(7)Recent research study has shown that low levels of Pregnancyassociated plasma protein A (PAPPA) during the first-trimester screening can be an independent risk factor for certain adverse pregnancy outcomes like spontaneous fetal loss before 24 weeks, intrauterine fetal death after 24 weeks, preeclampsia, preterm birth, gestational hypertension, and low birth weight. The PAPP-A levels less than the fifth percentile tend to have a high specificity. However, adverse pregnancy results were reported for low positive predictive values.(8)For pregnant women diagnosed with a low PAPP-A level, observing the fetal growth and Doppler indices can prove to be helpful in identifying high risk of adverse pregnancy outcomes. Even if the ultrasound scanning is normal it does not rule out an adverse obstetric outcome.

    Clinical Implications of low PAPP-A

    10. Causes of low PAPP-A in pregnancy:

    A lower PAPP-A level is associated with a higher incidence of maternal complications like pregnancy-induced hypertension and diabetes.(9)There is limited evidence which may suggest a relationship between low PAPP-A levels and spontaneous pregnancy loss in the woman. Recent studies suggest that low PAPP-A levels are directly associated with abnormal placentation, which can be the root cause of the adverse perinatal outcomes of interest. Several studies have also revealed that low PAPP-A can also be related to small babies, pre-eclampsia (high blood pressure and protein in urine) and early deliveries. An unborn baby is considered to be small when the size or weight of the baby, when checked in the ultrasound scan, is in the lowest 10 percent of babies. This may mean the smallest ten out of every 100 babies. Based on this situation, the national guidelines recommend that extra screening and scans should be considered to check the accurate growth of babies when a low PAPP-A level has been observed.(10)

    How to deal with a low PAPP-A level?

    It is being told that there is presently no medication or treatment for treating low PAPP-A, but to increase the chances for healthy and full-term baby delivery. The following lifestyle changes can prove to be helpful:

    • Eating healthy: More than genetic predisposition, the routine diet a pregnant woman eats during the crucial period of pregnancy, directly impacts the expression of her genes and the risk of inflammation in the body. Healthy eating habits have been linked to all metabolic diseases, including those a pregnant woman is more likely to develop during pregnancy. For those who are unsure of where to start from, must contact their healthcare provider for a healthy diet both the care of the mother and the fetus.
    • Relax: It might sound obvious, but a pregnant woman with a relaxed mind and body leaves a positive impact on the woman and her baby's health. So an expectant mother should try to stay calm and do what she can to manage stress, including exercise, meditation, or yoga. The baby is benefitted by the mother being relaxed. Relaxation minimizes the physical tension in a woman's body, which has a direct linkage with that of her baby.
    • Receiving required Vitamins and Minerals: Proper intake of vital minerals and vitamins is important for the normal functioning, development, and growth of a fetus. For a healthy pregnancy, adequate intake of protein, energy, minerals, and vitamins is required in order to meet maternal and fetal needs. (11)

    Notable points about Screening tests in Pregnancy:

    • Screening tests are routinely performed in the first trimester (first 3 months of pregnancy) or second trimester (4 to 6 months of pregnancy).
    • If the screening test results show the baby is at an increased risk, a woman may wish to have further diagnostic tests. Diagnostic tests are performed to confirm the presence of a condition and are very accurate.
    • Some diagnostic tests may increase the risk of pregnancy loss (miscarriage).
    • Screening and diagnostic tests during pregnancy cannot determine all health conditions.

    11. Frequently Asked Questions related to PAPP-A test:

    1. Why are PAPP levels low in Down Syndrome?
      Decreased levels of PAPP-A before the 14th week of pregnancy are associated with an increased risk for a chromosomal defect such as Down’s syndrome and Trisomy 18. The increased levels of hCG are associated with an elevated risk of Down syndrome.
    2. What are low PAPP-A levels associated with?
      Pregnancy-associated Plasma Protein A (PAPP–A) is a hormone which is produced by the placenta in pregnancy. Low levels of PAPP–A can be related to risks associated with certain chromosomal defects in the developing fetus. PAPP-A test can help in diagnosing certain chromosomal abnormalities to help a woman pursue a successful pregnancy.
    3. What is the normal range for PAPP-A levels?
      A Papp-A level more than or equal to 0.5 MOM is considered to be normal, while levels less than 0.5 MOM is considered to be low.
    4. What happens during nuchal translucency screening?
      A nuchal translucency screening is a special ultrasound. It is useful in measuring the baby's nasal bone as well as the fluid at the back of the baby's neck. A high volume of fluid can be an indication of problems. The combined result of the blood tests and the ultrasound in the first-trimester screening gives a result of the presence of a genetic disorder. Pregnancy and a successful delivery complete a family and give couples a chance to realize their dream of parenthood. However, there are several ups and downs that come in the process which should be dealt with utmost patience and courage by a couple. Couples should take things easy and must not let the results of a first-trimester screening test freak them out. For more information about PAPP-A blood test or any other information related to infertility or IVF procedure, visit or talk to our counselors and best fertility experts at +918268260808.

    1 Comment


    Harilal Naagesh

    June 7, 2019, 12:17 p.m. 4.5

    Leave a Comment



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