A selection of artificial neural network models were built and implemented for systematically study the contribution and the sensitivity of the main influencing parameters as important contributing factors for the non-invasive prediction of chromosomal abnormalities. The parameters that had been investigated are: the previous medical history of the pregnant mother, the nasal bone, the tricuspid flow, the ductus venosus flow, the PAPP-A value, the b-hCG value, the crown rump length (CRL), the changes in nuchal translucency (deltaNT) and the mother’s age. The main conclusions drawn are: 1) The deltaNT is the most significant factor for the overall prediction, while the CRL the least significant. 2) The previous medical history of the pregnant mother is not a significant factor for the prediction of the abnormal cases. 3) The nasal bone, the tricuspid flow and the ductus venosus flow contribute significantly in the prediction of trisomy 21 but not in the prediction of the “normal” cases. 4) The PAPP-A, the b-hCG and the mother’s age are of intermediate importance. Also, a sensitivity analysis of the attributes PAPP-A, b-hCG, CRL, deltaNT and of the mother’s age was done. This analysis showed that the CRL and deltaNT are more sensitive when their values are decreased, the PAPP-A is more sensitive when its values are increased and the b-hCG is insensitive to variations in its values.