Background and aim of work: Down syndrome (DS) is the mostcommonly recognized genetic cause of mental retardation. The risk of DS isdirectly related to maternal age. Women younger than 35 years should beoffered maternal serum screening at 16 to 18 weeks of gestation. Thematernal serum markers used to screen for DS are alpha-fetoprotein (AFP),unconjugated estriol (uE3) and human chorionic gonadotrophin (hCG). Theuse of ultrasound to estimate gestational age improves the sensitivity andspecificity of maternal serum screening. Our study aimed to establishEgyptian population-specific median values for each analyte used in thetriple test at each week of gestation between 15 to 20 weeks and tocompare these data with data obtained from other geographical regions andthe initial positive rate (IPR) was calculated.Methods: 431 pregnant females at least each group included 65 pregnantfemale in the second trimester (15-20) were recruited from the Obstetricsand Gynecology clinic of Cairo University hospital and the antenatal careclinic in the Center of Social and Preventive Medicine hospital, maternalserum was used to measure levels of AFP, HCG and uE3 using enzymeamplifiedchemiluminescent immunoassay (Immulite 2000)Results: We found that our medians among unaffected pregnancies forsecond trimester maternal serum AFP, hCG and uE3 differ from thoseevaluated in different population. At a risk cutoff of 1:270 the initialpositive rate (IPR) is slightly greater than that reported by many USlaboratories 6.5% using same test combination and same The IPR was greater when calculations were based on PRISCA default values,reaching 11.8%.Conclusions: For DS and NTDs, the risk calculated using current studymedians (BP diameter based) was lower than the risk based on LMP andPRISCA prenatal risk assessment software. However, NTDs was with nostatistical significance and DS was with high statistical significance. Fortrisomy 18, the risk calculated using current study medians was higher thanthe risk based on LMP and PRISCA. However the risk based on LMP waswith no statistical significance and the risk based on PRISCA was with highstatistical significance. And to Use our median based on BP diameterparticularly for DS and not to use software default values or medianpreviously calculated among different populations. Better to decide 1:270 asa risk cut-off for DS and to express this risk at sampling time.