title: Evaluation of population parameters and mathematical strategies for the calculation of prenatal risk of Down syndrome in the first trimester of pregnancy.
abstract: OBJECTIVE
  To evaluate the population parameters applied to the calculation of risk for Down syndrome (DS) in the first trimester screening (FTS) and the comparison of performance obtained including or excluding maternal age from the mathematical algorithm.
  
  
  METHODS
  Three different calculation engines for prenatal risk of DS were developed on the basis of the population parameters from the Serum, Urine and Ultrasound Screening Study, the Fetal Medicine Foundation, and a combination of both of them. These calculators were evaluated in 14,645 first trimester pregnant women, including 59 DS affected fetuses, comparing their performance with that obtained by our commercial software Elipse® (Perkin Elmer Life and Analytical Sciences, Turku, Finland). Advanced first trimester screening (AFS) strategy was also analyzed, and a hybrid strategy (FTS + AFS) was evaluated.
  
  
  RESULTS
  By selecting population parameters from the Serum, Urine and Ultrasound Screening Study, the detection rate increased from 76% (Elipse) to 86% with a small increase in the false positive rate (FPR), from 3.3% to 3.7%, respectively. DS screening performance significantly improved by using the hybrid strategy (AFS in pregnant women under 35 years and FTS in pregnant women over 35 years), with a 92% detection rate (FPR: 3.9%).
  
  
  CONCLUSIONS
  In the present study, a new hybrid screening strategy has been proposed to achieve DS detection rates higher than 90%, for a convenient <4% FPR.
authors.affiliation: Servicio de Bioquímica Clínica, Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Morillo
authors.forename: Belén Prieto
authors.initials: BP
authors.lastname: García
authors.forename: Francisco Moreno
authors.initials: FM
authors.lastname: Calvo
authors.forename: Francisco V
authors.initials: FV
authors.lastname: Alvarez
mesh_terms: D000293:Adolescent; D000328:Adult; D004314:Down Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D008403:Mass Screening; D008423:Maternal Age; D008875:Middle Aged; D008962:Models, Theoretical; D011153:Population; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000502:physiology / Q000652:urine; D011296:Prenatal Diagnosis / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography; D055815:Young Adult