title: Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester?
abstract: OBJECTIVE
  To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM) approach is the most appropriate method for calculating accurate individual patient-specific risks.
  
  
  METHODS
  Data on fetal NT and crown-rump length from 128,030 unaffected and 428 trisomy 21 pregnancies, measured by sonographers who had obtained The Fetal Medicine Foundation Certificate of Competence in the 11-14-Week Scan, were used. We examined first, if the distribution of NT MoM and log(10)(NT MoM) was Gaussian; second, if the standard deviation of the distributions did not change with gestation; and third, if the median MoM in the affected population was a constant proportion of the median for unaffected pregnancies. All of these features are required to underpin the MoM approach. NT distributions and those of delta-NT were also analyzed. A non-parametric kernel density method was then used to assess the validity of both methods. Errors in the estimation of individual patient-specific risks using the MoM approach were assessed.
  
  
  RESULTS
  In the unaffected pregnancies, the distributions of NT MoM and log(10)(NT MoM) were not Gaussian and the standard deviation of log(10)(NT MoM) decreased with gestation. In the trisomy 21 pregnancies, the median NT MoM decreased significantly with gestation, whereas the median delta-NT did not change with gestation. The non-parametric density approach showed that contours of constant likelihood ratio were parallel to the gestational age-dependent median NT values, thus supporting the delta-NT approach. The NT MoM approach resulted in women being given an overestimate of risk for trisomy at 11 weeks and a considerable underestimate of risk at 13 weeks.
  
  
  CONCLUSIONS
  In the calculation of risk for trisomy 21 by NT the NT MoM approach is inaccurate and inappropriate because the underlying assumptions are not valid. In contrast, the delta-NT approach gives accurate estimates of risks.
authors.affiliation: Clinical Biochemistry Department, Harold Wood Hospital, Romford, UK. KevinSpencer1@aol.com
authors.forename: K
authors.initials: K
authors.lastname: Spencer
authors.forename: R
authors.initials: R
authors.lastname: Bindra
authors.forename: A B J
authors.initials: AB
authors.lastname: Nix
authors.forename: V
authors.initials: V
authors.lastname: Heath
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D004314:Down Syndrome / Q000000981:diagnostic imaging*; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging*; D005865:Gestational Age; D006801:Humans; D009333:Neck / Q000000981:diagnostic imaging / Q000196:embryology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018570:Risk Assessment / Q000379:methods; D013223:Statistics as Topic; D016216:Ultrasonography, Prenatal / Q000379:methods*