Appropriate biochemical parameters in first-trimester screening for Down syndrome

Meta-analysis was used to calculate maternal serum marker distribution para meters for Down syndrome risk estimation in the first trimester. Data from 44 series were combined: relating to pregnancy associated plasma protein (P APP)-A in 18, free beta human chorionic gonadotrophin (hCG) in 17, alpha-fe toprotein (AFP) in 26 and unconjugated oestriol (uE(3)) in 9. All levels we re expressed in multiples of the normal median (MOM) for gestational age. I ndividual PAPP-A levels were available for 439 first and second-trimester D own syndrome pregnancies. The median MOM value increased with gestation: 0. 35 at 6-8 weeks (31 cases), 0.40 at 9-11 weeks (197), 0.62 at 12-14 weeks ( 113) and 0.94 thereafter (98). A cubic regression equation was fitted so it could be estimated for each week of gestation. For the other markers the m edian value in Down syndrome was estimated from the weighted mean across al l first-trimester series: 1.98 MOM for free beta-hCG in 579 cases; 0.79 MOM for AFP in 243 and 0.74 MOM for uE(3) in 226. Variance-ovariance matrices were calculated directly in unaffected pregnancies and from the difference between affected and unaffected pregnancies in Down syndrome. Based on thes e parameters we estimate that screening at 9-11 weeks with PAPP-A and free beta-hCG will yield a 64.6 per cent detection rate for a 5 per cent false-p ositive rate. Adding a third marker will increase detection to 66.6 per cen t for AFP and 68.6 per cent for uE(3); using all four markers it increases to 70.1 per cent. Routine ultrasound nuchal translucency measurement in add ition to serum testing will increase the rates to 86.4 per cent, 87.2 per c ent, 87.9 per cent and 88.3 per cent, respectively. Copyright (C) 1999 John Wiley & Sons, Ltd.