title: First-trimester screening for trisomy 21 with adjustment for biochemical results of previous pregnancies.
abstract: OBJECTIVE
  To investigate the effect of associations in serum free β-hCG and PAPP-A between successive pregnancies on the performance of screening for trisomy 21 at 11-13 weeks' gestation.
  
  
  METHODS
  In 8,499 women with two consecutive pregnancies, including 49 women with fetal trisomy 21 in the second pregnancy, the correlation in serum free β-hCG multiples of the median (MoM) and PAPP-A MoM between pregnancies was determined, and the effects of correcting for the correlation on the performance of screening was estimated.
  
  
  RESULTS
  There were significant associations between pregnancies in free β-hCG MoM (r = 0.4435) and PAPP-A MoM (r = 0.4796). In screening by maternal age and biochemistry at a risk cutoff of 1 in 100, in the second pregnancies the false-positive rate was 35.5% for those with screen-positive results in the first pregnancy, and this was reduced to 17.1% after adjustment for the results of the first pregnancy. Similarly, in women with screen-negative results in the first pregnancy, adjustment for the results improved the detection rate in the second pregnancy from 66.7 to 81.2%.
  
  
  CONCLUSIONS
  In screening for trisomy 21, adjustment for the biochemical findings in a previous pregnancy has major effects on individual patient-specific risks, increases the detection rate and reduces the false-positive rate.
authors.affiliation: School of Computing and Mathematics, University of Plymouth, Plymouth, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.forename: Argyro
authors.initials: A
authors.lastname: Syngelaki
authors.forename: Cahit
authors.initials: C
authors.lastname: Birdir
authors.forename: Ivonne
authors.initials: I
authors.lastname: Bedei
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008423:Maternal Age; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A