First Trimester Screening: pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG) free beta subunit

About the tests

The first trimester screen is a combination of two blood tests and a special ultrasound scan that are used to assess a pregnant woman's risk of carrying a baby with Down’s syndrome (trisomy 21) or other rarer fetal anomalies like Edward’s syndrome (Trisomy 18) or Patau’s syndrome (Trisomy 13). Analyzing biochemical markers together, along with the woman's age, increases the screening results' sensitivity and specificity.

• Pregnancy-associated plasma protein A (PAPP-A) is a protein produced first by the outer layer of the developing pregnancy (trophoblast) and then by the growing placenta. During a normal pregnancy, levels of this protein increase in the pregnant woman's blood until delivery. 

• Human chorionic gonadotropin (hCG) is a hormone produced by the developing pregnancy and then produced in large quantities by the placenta. The Free beta subunit is used in first-trimester screening. Levels usually rise rapidly in the pregnant woman's circulation for the first 8 to 10 weeks, then decrease and stabilize at a lower level for the rest of the pregnancy.

Nuchal translucency is a measurement made during the ultrasound scan. The ultrasonogram measures the fluid collection between the spine and the skin at the nape of the fetus's neck. It is a procedure that requires a specially trained sonographer, proper alignment of the fetus, and careful measurement.

Purpose of the test

The test must be performed between 11 and 14 weeks of pregnancy. 

A mathematical calculation using the results obtained from the PAPP-A and free beta hCG blood tests and the nuchal translucency measurement is used to determine a numeric risk of Down’s Syndrome or another fetal anomaly. 

Test results are very dependent on nuchal translucency techniques and the accurate determination of the fetus's gestational age. If the fetus's gestational age has not been accurately determined, the results may be either falsely high or low.

In twin pregnancies, it is still possible to perform first trimester combined screening using PAPP-A and hCG, although the accuracy of the test is lower. In triplet pregnancies, it is impossible to use combined screening, and the risk must be calculated using ultrasound measurements alone.