Table 5 shows that PAPP-A + free β-hCG + NT + AFP-L2 and PAPP-A + free β-hCG + AFP-L2 increased the IDI and NRI of predicting fetuses with trisomy 21 by 1.10% and 5.27% and 11.07% and 2.78%, respectively, after considering the maternal serum AFP-L2 level. This evidence concerns the gene PAPPA and trisomy 21.