title: Improvements in antenatal screening for Down's syndrome.
abstract: OBJECTIVE
  To estimate improvements to four antenatal screening tests for Down's syndrome (first trimester Combined, second trimester Quadruple, and first and second trimester Integrated and Serum Integrated tests) based on adding ductus venosus pulsatility index (DVPI), fetal nasal bone examination (NBE) and serum placental growth factor (PlGF).
  
  
  METHODS
  Statistical analysis of data from several sources modelled using the maternal age distribution of live births in England and Wales from 2006 to 2008.
  
  
  METHODS
  Monte Carlo simulation carried out to estimate the screening performance of tests with the addition of combinations of DVPI, NBE and PlGF.
  
  
  RESULTS
  At a 95% detection rate (DR), with first trimester markers measured at 11 completed weeks' gestation, the addition of DVPI, NBE and PlGF decreased the false-positive rate (FPR) of the Combined test from 16.1% to 3.0%, the addition of PlGF to the Quadruple test decreased the FPR from 15.7% to 15.3%, the addition of DVPI, NBE and PlGF to the Integrated test decreased the FPR from 4.1% to 0.6% and the addition of PlGF to the Serum Integrated test decreased the FPR from 15.1% to 11.1%. At a 90% detection rate, the reductions in the FPR were from 6.8% to 0.8%, 7.7% to 7.4%, 1.2% to 0.1% and 6.2% to 4.8%, respectively.
  
  
  CONCLUSIONS
  The addition of DVPI, NBE and PlGF to the Combined and Integrated tests significantly improves screening performance, reducing the FPRs by over 80%. The Integrated test with DVPI, NBE and PlGF is significantly better than the Combined test with DVPI, NBE and PlGF.
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. n.j.wald@qmul.ac.uk
authors.forename: N J
authors.initials: NJ
authors.lastname: Wald
authors.forename: J P
authors.initials: JP
authors.lastname: Bestwick
authors.forename: W J
authors.initials: WJ
authors.lastname: Huttly
mesh_terms: D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor