Among various routine tests, the PAPP-A values (Pregnancy-Associated Plasma Protein A) test plays a crucial role.
In this article, we will explore in detail what PAPP-A is, how it’s measured, what are normal and altered values, and what to do in case of abnormal results.
What is PAPP-A?
PAPP-A, or Pregnancy-Associated Plasma Protein A, is a fundamental substance during pregnancy. This protein plays a key role in several processes:
- Trophoblast implantation: PAPP-A is involved in the implantation of the cellular tissue that nourishes the embryo, called the trophoblast.
- Placental development: It contributes to the development and proper functioning of the placenta throughout pregnancy.
- Screening marker: It is used as a marker in screening tests for the most common fetal chromosomal abnormalities, such as Down syndrome and Edwards syndrome (trisomy 18).
PAPP-A was first identified in 1974 and has since become an essential element in prenatal tests.
Its concentration in maternal blood gradually increases as pregnancy progresses, then rapidly decreases after childbirth.
How and when is it measured?
PAPP-A measurement is done through a simple, non-invasive, and early blood test.
This test can be performed as early as the first trimester of pregnancy, typically between the 11th and 13th week + 6 days of gestation.
PAPP-A is often measured in combination with other markers, as part of more comprehensive screening tests:
- Combined test or Bi-test: This test evaluates the concentration of PAPP-A along with the free fraction of human chorionic gonadotropin (free-βhCG). It is performed between 11 and 13 weeks + 6 days of pregnancy and also includes an ultrasound examination to measure the length of the embryo and nuchal translucency.
- Integrated test: This test is conducted in two phases. The first phase, between the 11th and 13th week, includes PAPP-A testing. The second phase, between the 15th and 18th week, involves the triple test, which measures levels of estriol, alpha-fetoprotein, and human chorionic gonadotropin.
It’s important to note that these tests provide an estimate of the risk of chromosomal abnormalities, not a definitive diagnosis. Women should be clearly informed that screening offers a risk assessment, not diagnostic certainty.
What are the normal values?
PAPP-A values in maternal blood are detectable immediately after embryo implantation and double every 3-4 days during the first trimester, reaching maximum levels at the end of pregnancy.
To correctly interpret the results, PAPP-A values must always be correlated with the woman’s gestational age at the time of the blood draw.
The value obtained from the test is divided by the expected value for the gestational age in question. The unit of measurement used is MoM (Multiple of Median).
Normal PAPP-A values vary based on gestational age, but generally:
- A PAPP-A value considered normal is between 0.5 and 2.0 MoM.
- Values above 2.0 MoM are considered high but generally do not have pathological significance.
Regarding reference values for free beta hCG and PAPP-A, it’s important to note that these may vary slightly between laboratories. However, in general:
- Free beta hCG: normal values range between 0.5 and 2.0 MoM
- PAPP-A: normal values range between 0.5 and 2.0 MoM
What are altered values?
Altered PAPP-A values are primarily those that are low. Specifically:
- PAPP-A values below 0.5 MoM are considered low.
- PAPP-A values less than or equal to 0.4 MoM are considered particularly low and may be associated with an increased risk of various complications.
It’s important to emphasize that high PAPP-A values typically do not have pathological significance.
What are the consequences?
Low levels of PAPP-A in maternal blood can be associated with various conditions and risks:
- Fetal chromosomal abnormalities: In combination with other ultrasound and biochemical factors, low PAPP-A levels may indicate an increased risk of chromosomal abnormalities such as Down syndrome or Edwards syndrome.
- Low birth weight: Newborns of mothers with low PAPP-A levels may have below-average weight.
- Preterm birth: There’s an association between low PAPP-A levels and an increased risk of premature birth.
- Preeclampsia: Recent studies have shown a possible correlation between low PAPP-A levels and an increased risk of preeclampsia, especially early-onset.
- Spontaneous abortion: Low PAPP-A levels have been associated with an increased risk of miscarriage.
- Intrauterine growth restriction: Some studies suggest an association between low PAPP-A levels and an increased risk of fetal growth restriction.
- Intrauterine fetal death: In rare cases, low PAPP-A levels have been associated with an increased risk of fetal death in utero.
Furthermore, an Italian study conducted on over 3,000 cases has shown that low PAPP-A levels in the first trimester of pregnancy may also be associated with:
- Short stature in the child
- Development of maternal diabetes mellitus in later life
However, it’s important to note that these findings are still under study and it’s not yet possible to assign PAPP-A a definitive role in screening for future metabolic diseases in pregnant women.
What can be done if altered values are found?
If altered PAPP-A values are found, it’s crucial not to panic immediately. Here’s a list of things to do, that your gynecologist will likely recommend:
- Additional tests: The doctor may recommend further screening or diagnostic tests to better evaluate the situation. These might include:
- Additional blood tests
- Detailed ultrasounds
- Non-invasive fetal DNA testing
- Intensified monitoring: The doctor may recommend more frequent pregnancy monitoring, with regular ultrasound checks to assess fetal growth and well-being.
- Preeclampsia risk assessment: The doctor may advise preventive measures such as low-dose aspirin intake.
- Genetic counseling: In some cases, genetic counseling may be recommended to discuss more in-depth diagnostic options, such as amniocentesis or chorionic villus sampling.
- Psychological support: Dealing with uncertainty related to abnormal results can be stressful. Don’t hesitate to seek psychological support if you feel you need it.
- Healthy lifestyle: Maintaining a healthy lifestyle during pregnancy is always important, but becomes even more crucial in case of abnormal results. Follow a balanced diet, engage in moderate physical activity (if approved by your doctor), and avoid risky behaviors.
Remember that an altered PAPP-A value is not a definitive diagnosis of problems, but rather an indicator that requires further investigation. Many pregnancies with low PAPP-A levels proceed without complications and result in the birth of healthy babies.
We are with you.
At Parentalife, we understand how worrying it can be to receive abnormal results during pregnancy.
That’s why we are committed to supporting parents with our detailed guides, our informative courses, and by offering personalized consultations. Our goal is to provide you with the information and support you need to face every phase of your parenthood with serenity. Don’t hesitate to contact us for more information or support.
SOURCES
Shah KH, Anjum A, Nair P, Bhat P, Bhat RG, Bhat S. Pregnancy associated plasma protein A: An indicator of adverse obstetric outcomes in a South India population. Turk J Obstet Gynecol. 2020 Mar;17(1):40-45. doi: 10.4274/tjod.galenos.2020.05695. Epub 2020 Apr 6. PMID: 32341829; PMCID: PMC7171539.