title: Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies.
abstract: OBJECTIVE
  Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies.
  
  
  METHODS
  NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs.
  
  
  RESULTS
  In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5(th) centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT.
  
  
  CONCLUSIONS
  Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies.
authors.affiliation: Department of Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil. jmiguelez@yahoo.com
authors.forename: J
authors.initials: J
authors.lastname: Miguelez
authors.forename: M
authors.initials: M
authors.lastname: De Lourdes Brizot
authors.forename: A W
authors.initials: AW
authors.lastname: Liao
authors.forename: M H B
authors.initials: MH
authors.lastname: De Carvalho
authors.forename: M
authors.initials: M
authors.lastname: Zugaib
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004314:Down Syndrome / Q000097:blood / Q000000981:diagnostic imaging*; D005260:Female; D005865:Gestational Age; D006801:Humans; D009295:Nasal Bone / Q000000981:diagnostic imaging* / Q000196:embryology; D048208:Nuchal Translucency Measurement / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D018570:Risk Assessment; D016216:Ultrasonography, Prenatal / Q000379:methods*
chemical_list: D015415:Biomarkers