Temporal Changes in Maternal Serum Biochemical Markers of Trisomy 21 across the First and Second Trimester of Pregnancy

Abstract

There is significant temporal variation in mean log10MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.

Delta‐NT or NT MoM: which is the most appropriate method for calculating accurate patient‐specific risks for trisomy 21 in the first trimester?

“…The variation in SD of log 10 (NT MoM) with gestational age and the declining median NT MoM in trisomy 21 pregnancies clearly all add further evidence to the inappropriateness of the MoM approach, which ultimately leads to women being given inaccurate patient‐specific risks. Such temporal variation of marker MoMs has also been observed with first‐ and second‐trimester biochemical markers, but in general the distributions in the log 10 domain are Gaussian16. Nevertheless, it was suggested that to produce accurate patient‐specific risks the algorithms should no longer use the constant median separation model but they should be modified to a variable separation model in which each week of gestation has its own specific model parameters producing more accurate individual patient‐specific risks17.…”

Aneuploidy screening in the first trimester

“…A similar pattern was shown for free β‐hCG in the first trimester when levels increased from 1.75 at 11 weeks to 2.25 at 13 weeks and for PAPP‐A, the levels increased from 0.44 at 11 weeks to 0.69 at 13 weeks [Spencer et al, 1999b]. In a comprehensive analysis of data from between 700 and 1,000 cases with trisomy 21 and over 100,000 unaffected pregnancies Spencer et al [2002, 2003a] have described in detail the temporal variation across the first and second trimester for the markers AFP, PAPP‐A, free β‐hCG, and total hCG. The result of this temporal variation is that the separation between normal pregnancies and those with trisomy 21 is changing all the time.…”

“…The result of this temporal variation is that the separation between normal pregnancies and those with trisomy 21 is changing all the time. Using such a variable separation model prevents significant errors in individual patient‐specific risks when compared to a model where temporal change is not taken into account [Spencer et al, 2002, 2003a]. The other feature of such temporal variation is that for individual markers, there are key measuring periods.…”

“…Also repeat measures need not necessarily be restricted to cross trimesters. For example, a number of biochemical markers show temporal changes both within trimester and across trimester [Spencer et al, 2002, 2003a]. PAPP‐A progressively loses clinical discrimination from 8 weeks onwards.…”

Modeling Down syndrome screening performance using first‐trimester serum markers

“…Additionally, these rates can be improved by applying different first‐trimester screening strategies. Some markers are known to distinguish better between Down syndrome cases and controls, either earlier or later in the first trimester2, 3, 5, 9. Therefore, it may be appropriate to draw two separate blood samples in the first trimester and integrate these for the combined test (two‐sample combined test).…”