title: Combined sonographic and biochemical markers for Down syndrome screening.
abstract: OBJECTIVE
  To evaluate the efficacy of fetal nuchal fold thickness and proximal long bone biometric measurements in modifying Down syndrome serum screening risk in a population of women referred for second-trimester sonography.
  
  
  METHODS
  Sonographic biometric measurements and biochemical markers were combined retrospectively for 2533 women with known pregnancy outcomes. Four different screening methods were compared: (1) advanced maternal age; (2) biochemical serum screening markers; (3) modification of serum screening risks on the basis of categorical cutoffs for nuchal fold and femur and humerus length; and (4) a combined approach in which the sonographic measurements were treated as multiples of the medians and entered, together with the serum screening results, into a multivariable algorithm. The efficacy was compared at second-trimester risk cutoffs of 1:270 and 1:100.
  
  
  RESULTS
  Down syndrome was present in 30 of the 2533 pregnancies (1 in 84). With the use of the 1:270 cutoff, biochemical screening had 93% sensitivity and a 40% false-positive rate. With application of the categorical method of fixed cutoffs to incorporate fetal biometry, the false-positive rate was reduced to 33% with no loss of sensitivity. The combined model had 83% sensitivity and a 19% false-positive rate. The combined method had the highest positive predictive value (1 in 20). Similar gains in efficacy could be shown with the 1:100 cutoff.
  
  
  CONCLUSIONS
  For this high-risk group, the multivariate model that combines serum screening and sonography can result in a substantial reduction in the number of amniocenteses. Although the addition of the sonographic biometric measurements resulted in some Down syndrome cases being missed, the net effect was a large improvement in the overall positive predictive value of the screening.
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Maine Medical Center, Portland, Maine, USA. cartia@mmc.org
authors: Michael G
authors: MG
authors: Pinette
authors: James F X
authors: JF
authors: Egan
authors: Joseph R
authors: JR
authors: Wax
authors: Jacquelyn
authors: J
authors: Blackstone
authors: Angelina
authors: A
authors: Cartin
authors: Peter A
authors: PA
authors: Benn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D001699:Biometry; D004314:Down Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005260:Female; D005269:Femur / Q000033:anatomy & histology; D006801:Humans; D006811:Humerus / Q000033:anatomy & histology; D008423:Maternal Age; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D018566:Pregnancy, High-Risk; D011296:Prenatal Diagnosis; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014463:Ultrasonography
chemical_list: D015415:Biomarkers