Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages.
Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women > or =35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women > or =35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35-45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2 x 2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57-71% detection rates were achieved at 35 years with 12-18% false-positive rates. At 45 years, 61-100% detection rates were achieved with 66-95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35-45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed.
Muller
Françoise
F
Biochimie, Hôpital Ambroise Paré, AP-HP, 92104 Boulogne, France. francoise.muller@apr.ap-hop-paris.fr
Thalabard
Jean-Christophe
JC
Ngo
Sandrine
S
Dommergues
Marc
M
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D003198:Computer Simulation; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D011237:Predictive Value of Tests; D011247:Pregnancy / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards; D018570:Risk Assessment; D012984:Software; D000509:alpha-Fetoproteins / Q000032:analysis
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins