PAPP-A and β-hCG | The First-Trimester Biochemical Markers
When your doctor refers you for a “first-trimester biochemical screening,” this means two specific blood tests: measurement of PAPP-A and free β-hCG.
On their own, they are important indicators of pregnancy health; combined with the nuchal translucency ultrasound, they become one of the most reliable prenatal screening tools we have today.
What is β-hCG?
β-hCG (beta human chorionic gonadotropin) is the pregnancy hormone—the same one detected by a home pregnancy test. It is produced by the trophoblast (the tissue that forms the placenta) immediately after the fertilized egg implants in the uterus.
Its levels rise rapidly during the first weeks of pregnancy, doubling every 48–72 hours and reaching their peak around the 10th week, before gradually starting to decline.
In the context of combined first-trimester screening, we specifically measure free β-hCG, the form of the hormone that is not bound to other proteins and is a more reliable marker for calculating the risk of chromosomal abnormalities.
What is PAPP-A?
PAPP-A (Pregnancy-Associated Plasma Protein A) is a protein produced by the placenta and detected in the mother’s blood very early in pregnancy. Its levels increase gradually throughout gestation.
Its role in prenatal screening is significant.
Low PAPP-A levels in the first trimester have been associated with an increased risk of chromosomal abnormalities, as well as other pregnancy complications such as fetal growth restriction, preeclampsia, and preterm birth. For this reason, its evaluation is not limited to screening for chromosomal abnormalities but also has broader prognostic value for the course of the pregnancy.
Normal PAPP-A and β-hCG Values
When you receive your results, you will see a term next to your values that may seem confusing: MoM (Multiples of the Median). It is nothing complicated—it simply shows where your value lies in relation to the average value for your week
of pregnancy. A value of 1.0 MoM means exactly average; the acceptable range is considered to be 0.5–2.0 MoM.
In general:
- Low PAPP-A (below 0.5 MoM): may be associated with an increased risk of chromosomal abnormalities or pregnancy complications
- High β-hCG (above 2.0 MoM): may be a marker of increased risk for trisomy 21
- Low β-hCG: may be associated with a risk of trisomy 18 or 13
The most important thing to remember is this: an abnormal value on its own is not a diagnosis.
The two tests are always evaluated together, and in combination with the nuchal translucency measurement, your age, and other factors. The final result is a personalized risk estimate, not a simple “positive” or “negative” answer.
What Does Low PAPP-A Mean?
Low PAPP-A is a finding that often causes concern—without this always being justified. It is worth knowing the following:
First, a low PAPP-A value on its own is not enough to classify a pregnancy as “high risk.” It is always evaluated in combination with the rest of the findings from the combined test.
Second, even when low PAPP-A is linked to an increased risk of complications (such as growth restriction or preeclampsia), this does not mean these complications will occur, but rather that the pregnancy needs closer monitoring.
And that is exactly what we do: we design a personalized monitoring plan based on the overall findings.
When Is the Test Done and When Are the Results Ready?
The PAPP-A and β-hCG test is ideally performed between the 10th and 13th week and it is recommended to be done a few days before the nuchal translucency ultrasound, so that the results are ready and the combined risk calculation can be carried out on the spot during the scan.
Results are usually available within 1–3 working days after the blood sample is taken.
First β-hCG After Embryo Transfer
For couples who have undergone IVF, measuring β-hCG after embryo transfer—the so-called “first beta”—is a moment filled with anxiety and anticipation.
It is usually done 10–14 days after embryo transfer and confirms whether implantation has occurred. Here is what you should know:
- A positive β-hCG value confirms a biochemical pregnancy—but clinical confirmation is made with a viability ultrasound a few weeks later
- The absolute value of the first measurement is less important than its trend—that is, whether it doubles normally in subsequent tests
- A low initial value does not rule out a normal pregnancy; by contrast, a value that does not rise adequately requires careful monitoring
β-hCG in Twin Pregnancy – What Changes?
In a twin pregnancy, β-hCG levels are expected to be significantly higher than in a singleton pregnancy of the same gestational age, as two embryos produce a greater amount of the hormone. This is completely normal and not a cause for concern.
For this reason, interpretation of β-hCG values in a twin pregnancy is always based on specially adjusted reference ranges, and not on the same criteria used for singleton pregnancies.
Frequently Asked Questions (FAQ)
Typically, fasting is not required for a blood test measuring PAPP-A and β-hCG. However, because the test is often combined with other blood tests that may require fasting (such as glucose or lipids), it is recommended that you ask the laboratory or your doctor in advance for specific instructions.
If you are not having any other tests, however, you can eat and drink normally before the blood draw.
Yes—this is essentially what an over-the-counter pregnancy test does. However, a urine test simply gives a positive or negative result. For an accurate quantitative measurement—which is necessary both in prenatal screening and in follow-up after embryo transfer—a blood test is required.
Rarely, but yes. Very low levels of β-hCG may appear in certain pathological conditions, after a recent miscarriage, or in rare cases of neoplastic disease. That is why every result is always assessed in its clinical context and never in isolation.
It is worth noting that certain medications used to induce ovulation, such as chorionic gonadotropin (Ovitrelle, Pregnyl), contain synthetic β-hCG and can be detected in the blood for several days after administration. This means that taking such preparations—even without a medical prescription, as happens in some cases of self-administration for ovulation induction—may lead to a false-positive pregnancy test result. For this reason, every positive β-hCG result should always be interpreted in conjunction with the clinical history and, where considered necessary, repeated at a later time.
Yes, its diagnostic value for prenatal screening relates exclusively to the first trimester. After the 14th week, its levels continue to rise, but its measurement no longer has the same prognostic usefulness for chromosomal abnormalities.
Yes, and it is important for your doctor to know this. Pregnancies after IVF, egg donation, or progesterone use may affect PAPP-A and β-hCG values. That is why the method of conception and any medication taken are always considered during evaluation.
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