However, when it is used in combination with maternal age, NT, free β-HCG, and PAPP-A, it rises the DR of this screening up to 90%, with a false positive rate of 0.5%.28Moreover, regardless of whether it is directly associated with the modification of other variables in the screening or not, its frequency of presentation is higher in the fetuses with trisomy 21 and other chromosomal abnormalities than in the fetuses with normal genetical studies such as karyotype.29 This evidence concerns the gene PAPPA and trisomy 21.