title: Comparison of likelihood ratios of first-trimester nuchal translucency measurements: multiples of median, delta or mixture.
abstract: OBJECTIVE
  To compare the likelihood ratios (LR) determined for a measured nuchal translucency (NT) using the multiples of the median (MoM), delta-NT and mixture model approaches.
  
  
  METHODS
  This was a retrospective study of singleton pregnancies with known outcome screened at the 12(th) week of pregnancy between January 2006 and May 2008. NT, crown-rump length (CRL) and LR for trisomy 21 using the delta-NT approach (LRNT-delta) were extracted from The Fetal Medicine Foundation trisomy 21 risk-calculation software database. NT measurements were converted into their equivalent MoM by dividing by the expected CRL-specific median NT. LR for trisomy 21 based on the MoM (LRNT-MoM) of each case was then calculated as the ratio of the Gaussian probability density functions using published trisomy 21 risk-screening parameters. The LR using the mixture model (LRNT-mixture) was calculated as the ratio of individual composite probability densities reported for trisomy 21 and unaffected pregnancies. The intraclass correlation coefficient (ICC) was used to assess the agreement between the three different approaches while the paired t-test was used to perform pairwise comparisons.
  
  
  RESULTS
  Of the 5907 pregnancies with known outcome, 14 had trisomy 21. The ICC between the three approaches to determining an LR was 0.947 (95% CI, 0.943-0.951; P < 0.0001). Pairwise comparison indicated that differences between LR were statistically significant (P < 0.0001). Likelihood ratios determined via the delta-NT model were in general greater than those produced by both the mixture model (z = 5.58, P < 0.0001) and the MoM approaches (z = 32.8, P < 0.0001). For a 5% false-positive rate the detection rate of trisomy 21 (DR) was 78.6% (95% CI, 57.1-99.9%) The screen positive thresholds to achieve this DR were 1 : 200 for the delta-NT approach, 1 : 220 for the mixture approach and 1 : 290 for the MoM approach.
  
  
  CONCLUSIONS
  No single method of determining NT-associated LR outperformed the others in its ability to detect a trisomy 21-affected pregnancy.
authors.affiliation: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. daljit@cuhk.edu.hk
authors.forename: D S
authors.initials: DS
authors.lastname: Sahota
authors.forename: T Y
authors.initials: TY
authors.lastname: Leung
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: L W
authors.initials: LW
authors.lastname: Chan
authors.forename: T Y
authors.initials: TY
authors.lastname: Fung
authors.forename: T K
authors.initials: TK
authors.lastname: Lau
mesh_terms: D000328:Adult; D018568:Crown-Rump Length; D004314:Down Syndrome / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D048208:Nuchal Translucency Measurement / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011336:Probability; D012189:Retrospective Studies