Autocorrelation and cross-correlation between hCGβ and PAPP-A in repeated sampling during first trimester of pregnancy

Theoretically, repeated sampling of free β-human chorionic gonadotropin (hCGβ) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester of pregnancy might improve performance of risk assessment of trisomy 21 (T21). To assess the performance of a screening test involving repeated measures of biochemical markers, correlations between markers must be estimated. The aims of this study were to calculate the autocorrelation and cross-correlation between hCGβ and PAPP-A in the first trimester of pregnancy and to investigate the possible impact of gestational age at the first sample and time between sampling on the correlation. A prospective study was conducted including 3891 unaffected singleton pregnancies. Two measurements of hCGβ and PAPP-A were obtained during the first trimester in each pregnancy. Correlations between the four parameters, hCGβ first, hCGβ second, PAPP-A first and PAPP-A second, were estimated and presented in terms of Pearson’s r coefficients. Furthermore, the correlation between paired samples as a function of time between samples was investigated. The study demonstrated high correlation between first and second samples of hCGβ and PAPP-A with a correlation coefficient of 0.80 and 0.79, respectively. By contrast, the correlations between hCGβ and PAPP-A were low. In addition, the study demonstrated that the correlation between paired samples of hCGβ and PAPP-A decreases with earlier gestational age at the first sample and with increasing time between samples. We have developed a parameter set in terms of correlations between biochemical markers, which can be incorporated into a T21 screening algorithm based on repeated measures within the first trimester.