PAPPA and trisomy 18: Palomaki et al. [23] used a combination of serum markers (PAPP-A in early pregnancy and AFP, uE3, and free β-hCG in second pregnancy) to screen for trisomy 18 and reported a detection rate of 90% when the false-positive rate was 0.1%, which was reduced to 67% when PAPP-A in early pregnancy was removed from the analysis.