title: Analytical goal setting in aneuploidy screening: within person biological variability of first trimester biochemical markers.
abstract: OBJECTIVE
  To determine the average within person biological variability of free-β human chorionic gonadotrophin (free hCGβ), intact hCG and pregnancy-associated plasma protein A (PAPP-A), and to establish analytical goals for the measurement of these markers when used in first trimester screening.
  
  
  METHODS
  Free hCGβ, PAPP-A and intact hCG were measured on paired first trimester samples collected during the same pregnancy. Results were converted to Multiple of the Median (MoMs).The overall total variation at each day log was determined from a correlation of the marker MoMs in the log domain. Biological variation was calculated after taking into account analytical variation.
  
  
  RESULTS
  The within person biological variability for free hCGβ varied from 1.30% at 2 days separation to 5.25% at 5 days. For PAPP-A this was 1.96% and 5.03%, respectively, and for intact hCG this was 14.59% and 21.09%. All markers exhibit a rapid increase in biological variability as the time separation increased.
  
  
  CONCLUSIONS
  Setting analytical goals for precision of measurement of first trimester biochemical markers from within person biological variability would suggest that free hCGβ and PAPP-A needs to be measured with a precision of 2.5%, targets close to those set empirically by the Fetal Medicine Foundation and achieved in practice by some analytical system in routine use.
authors.affiliation: Prenatal Research Unit, Department of Clinical Biochemistry, King George Hospital, Barley Lane, Goodmayes, IG3 8YB, UK. KevinSpencer1@aol.com
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Cowans
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis / Q000379:methods*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human