The impact of temporal variability of biochemical markers PAPP-A and free β-hCG on the specificity of the first-trimester Down syndrome screening: a Croatian retrospective study

BACKGROUND: The variability of maternal serum biochemical markers for Down syndrome, free β-hCG and PAPP-A can have a different impact on false-positive rates between the 10+0 and 13+6 week of gestation. The study population comprised 2883 unaffected, singleton, spontaneously conceived pregnancies in Croatian women, who delivered apparently healthy child at term. Women were separated in 4 groups, dependently on the gestational week when the analyses of biochemical markers were performed. The concentrations of free β-hCG and PAPP-A in maternal serum were determined by solid-phase, enzyme-labeled chemiluminiscent immunometric assay (Siemens Immulite). Concentrations were converted to MoMs, according to centre-specific weighted regression median curves for both markers in unaffected pregnancies. The individual risks for trisomies 21, 18 and 13 were computed by Prisca 4.0 software. FINDINGS: There were no significant differences between the sub-groups, regarding maternal age, maternal weight and the proportion of smokers. The difference in log(10 )MoM free β-hCG values, between the 11(th )and 12(th )gestational week, was significant (p = 0.002). The difference in log(10 )MoM PAPP-A values between the 11(th )and 12(th), and between 12(th )and 13(th )week of gestation was significant (p = 0.006 and p = 0.003, respectively). False-positive rates of biochemical risk for trisomies were 16.1% before the 11(th )week, 12.8% in week 12(th), 11.9% in week 13(th )and 9.9% after week 13(th). The differences were not statistically significant. CONCLUSIONS: Biochemical markers (log(10 )MoMs) showed gestation related variations in the first-trimester unaffected pregnancies, although the variations could not be attributed either to the inaccuracy of analytical procedures or to the inappropriately settled curves of median values for the first-trimester biochemical markers.