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  • Title: Appropriate biochemical parameters in first-trimester screening for Down syndrome.
    Author: Cuckle HS, van Lith JM.
    Journal: Prenat Diagn; 1999 Jun; 19(6):505-12. PubMed ID: 10416963.
    Abstract:
    Meta-analysis was used to calculate maternal serum marker distribution parameters for Down syndrome risk estimation in the first trimester. Data from 44 series were combined: relating to pregnancy associated plasma protein (PAPP)-A in 18, free beta human chorionic gonadotrophin (hCG) in 17, alpha-fetoprotein (AFP) in 26 and unconjugated oestriol (uE3) in 9. All levels were expressed in multiples of the normal median (MOM) for gestational age. Individual PAPP-A levels were available for 439 first and second-trimester Down 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 median value in Down syndrome was estimated from the weighted mean across all 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 uE3 in 226. Variance-covariance matrices were calculated directly in unaffected pregnancies and from the difference between affected and unaffected pregnancies in Down syndrome. Based on these 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-positive rate. Adding a third marker will increase detection to 66.6 per cent for AFP and 68.6 per cent for uE3; using all four markers it increases to 70.1 per cent. Routine ultrasound nuchal translucency measurement in addition to serum testing will increase the rates to 86.4 per cent, 87.2 per cent, 87.9 per cent and 88.3 per cent, respectively.
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