Pregnancy Associated Plasma Protein –A
First Trimester Screening for Trisomy 21 & 18
PAPP-A was first described in 1974 as a high molecular weight component of serum obtained from individuals in late pregnancy.
The biological function of PAPP-A is still unclear. It has been shown to bind heparin which has led to the postulation that it may have a role in modulating the maternal immune response and be associated with implantation and growth of the placenta.
Much of the initial work of PAPP-A in the early 1980s was based on the finding that low levels of PAPP-A were associated with poor fetal viability, miscarriage, pregnancy induced hypertension and growth retardation.
The recent observation of PAPP-A in unstable atherosclerotic plaques, along with increased circulating levels, may suggest a new role for PAPP-A as a marker of acute coronary syndromes. To date, however, its major clinical usefulness appears to be limited to a marker of chromosomal aneuploidy, and as an indicator of early pregnancy failure and pregnancy complications.
The most common chromosomal abnormality is trisomy 21 (Down syndrome); its risk is increasing dramatically with maternal age. The second trimester incidence of trisomy 21 is now 1:500. Other common chromosomal aneuploidies include trisomy 18 and trisomy 13.
Since the early 1990s, prenatal screening, initially instituted for detection of trisomy 21, has become a standard part of obstetric practice through measurement of maternal serum biochemical markers in the 2nd trimester (15 to 22 weeks gestation). These markers include: AFP- total HCG, free B-HCG and unconjugated estriol. Using a combination of maternal age and these markers, detection rate of 65 - 70% can be achieved with 5 - 6% false positive rate.
Most of the research in the past decade has been focused on screening earlier in pregnancy (9 to 14 weeks). PAPP-A is a good first trimester marker, while total HCG is a second trimester marker. Free B-HCG is relatively stable from 9-18 weeks and the best clinical use for PAPP-A may be as early as 8 weeks. Therefore, the best time to measure both PAPP-A & free B-HCG is in the first trimester between 9 and 14 weeks.
When used in conjunction with free B-HCG, PAPP-A can detect 90% of trisomy 13 and trisomy 18 cases at only 1% false positive rate.