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Pregnancy Associated Protein A (PAPP-A)
Last reviewed: 06.07.2025
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Reasons for decreased PAPP-A
In case of fetal chromosomal abnormalities, the PAPP-A content in the blood serum in the first and early second trimesters of pregnancy (8-14 weeks) is reduced in two thirds of women. The sharpest decrease in the concentration of this protein is observed in trisomies of chromosomes 21, 18 and 13. Anomalies of the sex chromosomes in the fetus are also often accompanied by a decrease in the PAPP-A content in the pregnant woman's blood serum. A change in the PAPP-A concentration is also possible with trisomy of chromosome 22. The prognostic value of PAPP-A for detecting fetal abnormalities is higher than the change in the levels of such well-known markers as AFP, hCG, trophoblastic β 1 -globulin, as well as unconjugated estriol and inhibin A, and is comparable to that for free β-hCG. A decrease in the PAPP-A level in case of fetal chromosomal abnormalities is most pronounced at 10-11 weeks of pregnancy.
Serum PAPP-A Median Concentration Values for Screening Congenital Malformations
Gestational age, weeks |
Median PAPP-A concentration, mg/L |
8 |
1.86 |
9 |
3.07 |
10 |
5.56 |
11 |
9.86 |
12 |
14.5 |
13 |
23.4 |
14 |
29.1 |
An even sharper decrease in the concentration of PAPP-A in the blood serum of a pregnant woman is observed in the presence of Cornelia de Lange syndrome in the fetus, in which, as with autosomal trisomies, multiple dysplasias, developmental defects, and delayed psychomotor and physical development are observed.
Another independent pathognomonic symptom of fetal aneuploidy at the end of the first trimester of pregnancy is thickening of the nuchal fold, which is detected by ultrasound examination, but visualization of this form of local soft tissue edema is quite complex and subjective even when using modern scanner models with high resolution. It should be noted that early verification of fetal trisomy after ultrasound or biochemical screening and subsequent karyotyping of cytotrophoblast obtained by chorionic biopsy allows terminating pregnancy already in the first trimester. In the second trimester, verification of fetal aneuploidy is carried out by karyotyping of fibroblast-like cells from amniotic fluid.