The variation of risk estimates through pregnancy in second trimester maternal serum screening for Down syndrome.
The variation of risk estimates in second trimester maternal serum screening for Down's syndrome has been shown to be considerable in quality control schemes, i.e. UKNEQAS. We studied the biological variation of risk estimates in 16 women through pregnancy. The maternal serum markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3) and beta-hCG were determined six times during late first to late second trimester, and the associated likelihood ratios for Down syndrome were calculated. The interpersonal variation of markers, as well as that of the likelihood ratio, was much greater than the intrapersonal variation. The average intrapersonal standard deviation (SD) of the triple test log likelihood ratio was 0.2291, corresponding to a central 95-percentile interval 0.36-2.81 of the likelihood ratio. The interpersonal SD of the log likelihood ratio was 0.5482, corresponding to a central 95-percentile interval 0.08-11.87 of the likelihood ratio. The large difference between the intra- and interpersonal variation makes it unlikely that biological variation through pregnancy is a major contributor to the variation of risk estimates obtained several times in the same pregnancy. Rather, improvements in analytical quality and laboratory management must be expected to result in reduced variation and, in consequence, better performance of screening.
Christiansen
Michael
M
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark. mic@ssi.dk
Høgdall
Estrid V
EV
Larsen
Severin O
SO
Høgdall
Claus
C
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D006063:Chorionic Gonadotropin / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000517:prevention & control*; D004964:Estriol / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D016013:Likelihood Functions; D008403:Mass Screening / Q000379:methods*; D011247:Pregnancy / Q000097:blood*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D018570:Risk Assessment / Q000706:statistics & numerical data; D000509:alpha-Fetoproteins / Q000032:analysis
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; D004964:Estriol