Abstract for presentation at 11th International Congress of Human Genetics

The proform of eosinophil major basic protein (ProMBP) and SP1 are efficient maternal serum markers for Down's syndrome in gestational week 6-8

  • Michael Christiansen, Statens Serum Institut, Copenhagen, Denmark
  • Dr Michael Overgaard, Department of Molecular Biology, Aarhus University, Denmark
  • Dr Christian Ensinger, Department of Pathology, University of Innsbruck, Austria
  • Dr Bent Nørgaard-Pedersen, Statens Serum Institut, Copenhagen, Denmark
  • Dr Claus Oxvig, Department of Molecular Biology, Aarhus University, Denmark

    • The proform of eosinophil major basic protein (ProMBP) and pregnancy-specific glycoprotein-1 (SP1) are both synthesised by the placenta. ProMBP exists in the circulation as complexes with angiotensinogen and pregnancy-associated plasma protein-A (PAPP-A). We tested the performance of total ProMBP, angiotensinogen/ProMBP and SP1 as early first trimester maternal serum markers of Down's syndrome. The concentrations of total ProMBP and angiotensinogen/ProMBP were measured by ELISA in 39 women with a Down's syndrome fetus and 123 women with unaffected fetuses (controls), obtained in week 4-14 of gestation, and the distribution of gestational age independent multiples of the median for each gestational age (MoMs)was determined for each analyte. Only the total ProMBP was significantly (p = 0.015) reduced with a median MoM of 0.70 and only in week 6-8. Using a published standardised age-distribution of pregnant women and published a priori risks for giving birth to a DS child, the detection rate (DR) for DS was estimated by Monte Carlo simulation to be 41% for a 5% false positive rate (FPR) using total ProMBP and age as markers. The combination of ProMBP, SP1 determined in week 6-8 and nuchal translucency(NT) determined in week 11-13 was estimated to have a DR of 84% for a FPR of 5% and a DR of 71% for a FPR of 1%. Using a risk cut-off for giving birth to a DS child of 1:400 gave a DR of 83% for a FPR of 3.9% using the combined ProMBP, SP1, NT and age combination. ProMBP+SP1+age gave a DR of 68% for a FPR of 9.6%.
    In conclusion, it is possible to perform serological screening for Down's syndrome in week 6-8, as efficiently as with the second trimester tripletest, using the markers ProMBP and SP1. The markers SP1 and ProMBP could probably be used in conjunction with other early first trimester markers, e.g. PAPP-A and ADAM12, and hereby make it possible to perform a satisfactory serological screening for Down's syndrome prior to week 9.

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