title: Erroneous production of PAPP-A kits: the impact of a downward shift in PAPP-A concentration on the test performance of first-trimester combined screening for Down syndrome.
abstract: OBJECTIVE
  To evaluate a 20% downward shift in the pregnancy-associated plasma protein A (PAPP-A) concentration on the test performance of first-trimester combined screening (FTS) for Down syndrome (DS) following a flaw in the production of PAPP-A kits on FTS for DS.
  
  
  METHODS
  A retrospective re-evaluation of PAPP-A in stored sera. Inclusion criteria were a maternal weight-corrected PAPP-A multiple of the median value ≥ 0.9 and a biochemical risk of DS ≤ 1:200 at the time of testing.
  
  
  RESULTS
  Of the 3100 women, 473 (15%) fulfilled the inclusion criteria. After combining the biochemical risk based on the incorrect PAPP-A values with nuchal translucency findings, an increased risk for DS was initially found in 107 women [false positive rate (FPR): 3.1]. Eighty-two (77%) of the 107 women opted for invasive testing. Following re-analysis of PAPP-A, the biochemical risk and the combined risk were statistically significantly different from the initial risk estimates (p < 0.001.). We noticed that 25 women (30%) had invasive testing, while this was unjustified given the re-analysed PAPP-A.
  
  
  CONCLUSIONS
  Erroneous PAPP-A kits resulted in an increase in the FPR by 1.2%. There were no reports of iatrogenic miscarriage. The occurrence of this problem reaffirms the importance of continuous monitoring of quality in FTS.
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, University Medical Center, Rotterdam, The Netherlands. p.vanheesch@erasmusmc.nl
authors.forename: P N A C M
authors.initials: PN
authors.lastname: van Heesch
authors.forename: Y B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: J A M
authors.initials: JA
authors.lastname: Laudy
authors.forename: H I J
authors.initials: HI
authors.lastname: Wildschut
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000592:standards*; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A