title: Maternal weight correction of maternal serum PAPP-A and free beta-hCG MoM when screening for trisomy 21 in the first trimester of pregnancy.
abstract: OBJECTIVE
  To assess the suitability of either the log-linear or reciprocal-linear regression procedure for maternal weight correction of biochemical marker MoMs in the first trimester.
  
  
  METHODS
  Data from two prospective first-trimester OSCAR screening programmes including 32,010 women with first-trimester maternal serum-free beta-hCG and PAPP-A measured by the Kryptor analyser was analysed by regression analysis to provide parameters for the log-linear and reciprocal-linear MoM correction procedures. Assessment was made by goodness of fit to the data. The impact on detection rate and false-positive rate of the different correction procedures was assessed using statistical modelling with biochemical markers alone.
  
  
  RESULTS
  Both log-linear and reciprocal-linear correction were shown to fit the data well. For free beta-hCG, the log-linear procedure was marginally superior to the reciprocal-linear procedure (r2=0.986 v 0.980), whilst for PAPP-A the reciprocal-linear procedure was marginally better (r2=0.991 v 0.985). Log-linear correction reduced the variance for both markers more than did the reciprocal-linear procedure. For free beta-hCG, the sd was reduced from 0.2675 to 0.2605 and for PAPP-A, it was reduced from 0.2545 to 0.2336. Correcting for maternal weight was shown to reduce the population false-positive rate from 7.0 to 6.5%, whilst maintaining the same detection rate at a risk cut-off of 1 in a 100. At individual levels, a two-fold variation in risk was demonstrated depending upon the individual's weight.
  
  
  CONCLUSIONS
  To provide accurate individual patient-specific risks for trisomy 21, maternal weight must be taken into account and should be a mandatory data item for screening programmes. Maternal weight correction in the first trimester using free beta-hCG and PAPP-A can be best achieved using the log-linear procedure.
authors.affiliation: Clinical Biochemistry Department, Harold Wood Hospital, Gubbins Lane, Romford, Essex, UK. KevinSpencer1@aol.com
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Renu
authors.initials: R
authors.lastname: Bindra
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D015415:Biomarkers; D001835:Body Weight; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000706:statistics & numerical data*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A