Email updates

Keep up to date with the latest news and content from BMC Research Notes and BioMed Central.

Open Access Short Report

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

Dubravka Tišlarić-Medenjak1*, Ivana Zec1, Ana-Maria Šimundić2, Senka Sabolović-Rudman3, Milan Kos4 and Željka Bukovec Megla1

Author Affiliations

1 Laboratory of Endocrinology, Clinics of Oncology and Nuclear Medicine, University Hospital "Sestre milosrdnice", Zagreb, Croatia

2 University Department of Chemistry, University Hospital "Sestre milosrdnice", Zagreb, Croatia

3 Clinics of Gynecology and Obstetrics, University Hospital "Sestre milosrdnice", Zagreb, Croatia

4 Out-patient Clinics of Gynecology "VILI", Zagreb, Croatia

For all author emails, please log on.

BMC Research Notes 2010, 3:194  doi:10.1186/1756-0500-3-194

Published: 14 July 2010



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.


There were no significant differences between the sub-groups, regarding maternal age, maternal weight and the proportion of smokers. The difference in log10 MoM free β-hCG values, between the 11th and 12th gestational week, was significant (p = 0.002). The difference in log10 MoM PAPP-A values between the 11th and 12th, and between 12th and 13th 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 11th week, 12.8% in week 12th, 11.9% in week 13th and 9.9% after week 13th. The differences were not statistically significant.


Biochemical markers (log10 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.