Pregnancy-associated plasma protein-A

From Embryology


Prenatal diagnosis- novel serum biomarker screening

Pregnancy-associated plasma protein-A (PAPP-A) largest of the pregnancy associated proteins produced by both the embryo and the placenta (syncytiocytotrophoblasts) during pregnancy (Placenta Notes). This protein is thought to have several different functions, including preventing recognition of the fetus by the maternal immune system, matrix mineralization and angiogenesis. Levels of PAPP-A rise from first detection in the first trimester until term.

Detection of this protein is also suggested as a first and second trimester diagnostic test for aneuploidies, including Trisomy 21 or Down Syndrome.

Maternal serum concentrations are related to subsequent fetal growth and this relationship has suggested that it can be used as a diagnostic test for adverse pregnancy outcomes (intrauterine growth restriction, premature birth, preeclampsia, and stillbirth).

Alternative names: pappalysin 1, PAPP-A, PAPPA1, SP4, high molecular weight alpha-2 mobile pregnancy-specific protein, IGFBP4 protease (IGFBP-4ase), ASBABP2, DIPLA1, PAPA

Diagnosis Links: Prenatal Diagnosis | pregnancy test | amniocentesis | chorionic villus sampling | ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

| Trisomy 21 | Original PAPP-A page

PAPP-A Levels

  • Levels of PAPP-A rise from initial detection at about 32 days after ovulation, then increasing rapidly (levels doubling every 3 days), finally continuing to rise more slowly until term.
  • Electroimmunoassays allow the detection as early as the fifth week of pregnancy, of circulating levels down to 10 microgram/L.
  • Adult male serum PAPP-A circulating level is 8.03±2.75 mIU/L (mean±SD).

Maternal serum level

  • increased PAPP-A indicate increased risk of trisomy 21
  • reduced PAPP-A associated with an increased risk of trisomy 18
  • First trimester low PAPP-A (< 0.4 MoM) associated with an increased frequency of adverse obstetrical outcomes.[1]


  • large zinc glycoprotein[2][3]
  • secreted metalloproteinase (EC= which cleaves insulin-like growth factor binding proteins (IGFBPs).
    • specifically cleaves IGFBP-4 and IGFBP-5, releasing bound IGF
  • present in pregnancy serum
    • heterotetrameric 2:2 complex with proform of eosinophil major basic protein (proMBP).[4]
    • approximate 500 kDa complex called PAPP-A/proMBP.
  • placental origin
  • also in: ovarian follicles, follicular fluid, luteal cells
    • uterine tubes of nonpregnant women
    • seminal vesicles and seminal fluid of males

Links: OMIM | GeneCards | UniProtKB/Swiss-Prot


  1. Gagnon A & Wilson RD. (2008). Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can , 30, 918-932. PMID: 19038077 DOI.
  2. Kristensen T, Oxvig C, Sand O, Møller NP & Sottrup-Jensen L. (1994). Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA. Biochemistry , 33, 1592-8. PMID: 7508748
  3. Haaning J, Oxvig C, Overgaard MT, Ebbesen P, Kristensen T & Sottrup-Jensen L. (1996). Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP. Eur. J. Biochem. , 237, 159-63. PMID: 8620868
  4. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L & Oxvig C. (2003). Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. J. Biol. Chem. , 278, 2106-17. PMID: 12421832 DOI.

Search PubMed: Pregnancy-associated plasma protein-A

Prenatal Diagnosis Terms

  • blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
  • blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
  • cell-free fetal deoxyribonucleic acid - (cffDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood.
  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.
  • multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
  • polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • pre-implantation genetic diagnosis - (PGD, pre-implantation genetic screening) a diagnostic procedure for embryos produced through Assisted Reproductive Technology (ART, in vitro fertilisation, IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
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Cite this page: Hill, M.A. (2019, December 16) Embryology Pregnancy-associated plasma protein-A. Retrieved from

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G