SECOND TRIMESTER (15-20 WEEKS)
The first protein routinely measured in the maternal blood was AFP (alpha-fetoprotein). High AFP levels were originally used to identify fetuses at risk for neural tube defects. In 1984 it was reported by Merkatz et al that low AFP levels may help identify fetuses with Down syndrome as well as fetuses with trisomy 18. AFP remains one of the proteins used for screening during the second trimester, but it is actually one of the least useful markers. Also screening for elevated AFP levels is a now poor method of screening for neural tube defects where high quality obstetric ultrasound is available. It remains useful where high quality obstetric ultrasound is not available or not applied.
HUMAN CHORIONIC GONADOTROPIN (HCG)
The second useful blood test was high levels of HCG, reported by Bogart et al in 1987. This is the same protein used for pregnancy testing, although it turns out there are many different forms of this protein. HCG or a another form (free beta HCG) is one of the most useful of the blood markers and it is the only one that works in both the second and the first trimester.
levels of estriol were reported to be associated with an increased risk
for Down syndrome by Cannick in 1998. Addition of estriol to the other
2 markers produced a panel of markers which was commonly referred to as
the "triple screen". This model was proposed by Wald in the late 1980s
and it became the primary method for screening in the United States
through out the 1990s. The addition of estriol showed only a small
incremental benefit, however, to the other 2 markers and use of estriol
was a controversial topic. In Great Britain, estriol was not added so
the standard was using a "dual" marker panel of AFP and HCG. The triple
screen had a detection rate of about 65% for a 5% false positive rate.
Differences in inhibin
A levels were observed in the early 1990s. However, the assay was
unstable and could not be used in a practical way until the late 1990s.
Addition of inhibin-A to the triple screen resulted into the so called
"quad screen”. The quad screen can detect 70-75% of cases of fetal
FIRST TRIMESTER (9-14 WEEKS)
It is important to know that these proteins change during pregnancy, so interpretation requires an knowledge of the gestational age. Also, the effectiveness of these proteins varies with gestational ages. For example, differences in protein levels may be observed during the second trimester but not the first, while other proteins show differences during the first trimester but not the second.
FREE BETA HCG
There are many metabolites of HCG. One of these is free beta HCG. Elevated levels of free beta HCG can be used during the first trimester to help screen for fetal Down syndrome.
PAPP-A (PREGNANCY ASSOCIATED PLASMA PROTEIN-A)
Low levels of PAPP-A were found to be associated with fetal chromosome abnormalities during the early 1990s. This is one of the most useful blood marker during the first trimester.