Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy

Background Many maternal serum markers show concentration changes in Down's syndrome pregnancies but the magnitude of the change in median marker levels varies with gestation. To date these changes have not been accurately specified. Methods The trends in marker median levels between 6 and,20 weeks of gestation were examined for alphafetoprotein (AFP), free beta human chorionic gonadotrophin (Fbeta-hCG), total human chorionic gonadotrophin (ThCG) and pregnancy-associated plasma protein A (PAPP-A) by a meta-analysis of data obtained from our collaborative studies and routine screening programmes for Down's syndrome over a 10-year period. Data were available from between 709 and 1082 Down's syndrome pregnancies and from between 14 607 and 153 909 unaffected pregnancies for each marker. The median multiple of the median (MoM) and mean log(10)MoM for each marker at each completed week of gestation were estimated and the trend with gestation smoothed using a weighted least squares regression model. Results The gestational ages at which maximum separation of marker levels occurred, comparing affected and unaffected pregnancies, and the respective regressed median MoMs and mean log(10)MoMs, were: for AFP at 16 weeks, 0.72 MoM, -0.14288 log(10)MoM; for Fbeta-hCG at 15 weeks, 2-24 MoM, 0.35034 log(10)MoM; for ThCG at 16 weeks, 1.93 MoM, 0.28548 log(10)MoM, as well as before 8 weeks (<0.65MoM, -0.18853log(10)MoM); and for PAPP-A before 8 weeks, <0.33MoM, -0.47727log(10)MoM. Conclusion There is significant temporal variation in mean log(10)MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.