The "integrated screen" is a first trimester screen plus a 2nd trimester biochemical screen. The first trimester screen consists of ultrasound measurements (crown rump length and nuchal translucency) plus one biochemical marker (PAPP-A). HCG is not measured in this first trimester protocol since HCG is part of the 2nd trimester screen. The 2nd trimester biochemical screen consists of a "quad" screen (AFP, HCG, estriol, and inhibin-A). Of course, maternal age is also considered in the risk estimates. The integrated screen was proposed by Nick Wald and he has patented this approach.

The integrated screen requires that the patient first present at 11-14 weeks for an ultrasound and blood draw (or finger stick) and then return at 14-20 weeks for the 2nd trimester biochemical screen.  Only then are the results integrated and the patient is given a single risk estimates. Although this method has more complicated logistics, it theoretically should provide the highest accuracy rate.  Note that if the patient needs to know the results after the first trimester exam, this would not be an integrated screen but rather a first trimester screen.  If a 2nd trimester biochemical screen is also performed, this would be a sequential or step wise screen (described below).


The sequential or step wise screen consists of a first trimester screen followed by a 2nd trimester screen.  Unlike an integrated screen which reports a single risk estimate, the step wise screen would report a result from both the first trimester screen and the second trimester screen separately.  Patients would be considered to have a positive screen if either the first trimester screen OR the 2nd trimester screen are positive.  This method has a high detection rate but also a high false positive rate.  This method might be selected for patients initially considered "high risk" before the screening methods- these patients might consider diagnostic testing unless both the first and second trimester screen are negative.


A number of proteins in the maternal circulation have been found during the time of pregnancy.  Many of these are made or modified by the placenta.  Differences in levels of some of the proteins have been observed in patients carrying a fetus with Down syndrome and certain other chromosome abnormalities.  The discovery of these slight differences in protein levels has been largely based on observation- we really don't know why they work in most cases.  Nevertheless, we can take advantage of these differences in screening protocols.

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.


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.


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.