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Combined Sonographic and Biochemical Markers for Down Syndrome Screening

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Maine Medical Center, Portland, Maine USA (M.G.P., J.R.W., J.B., A.C.); Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, St Francis Hospital and Medical Center, Hartford, Connecticut USA (J.F.X.E.); and Division of Human Genetics, Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut USA (P.A.B.).

Address correspondence and reprint requests to Michael G. Pinette, MD, MMC Ob/Gyn Associates, 887 Congress St, Suite 200, Portland, ME 04102. E-mail: cartia{at}mmc.org.

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.

Key Words: biochemical markers • Down syndrome • sonography

Abbreviations: AFP, -fetoprotein • BPD, biparietal diameter • CI, confidence interval • E3, estriol • FL, femur length • hCG, human chorionic gonadotropin • HL, humerus length • MoM, multiple of the median • NF, nuchal fold

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