Effect of incorrect gestational dating on Down's syndrome and neural tube risk assessment

Down's syndrome risks are estimated between 15 and 20 completed weeks' gestation (cGW) using an algorithm involving maternal age and serum alpha-fetoprotein (AFP), chorionic gonadotrophin and unconjugated oestriol levels, each expressed as a multiple of the median level (MoM) at the cGW. The AFP MoM itself is the basis for screening for open neural tube defects (oNTD). Because medians change during this period, gestational dating must be accurate so that appropriate medians are used. A calculated Down's syndrome risk > 1:380 at term is generally considered to indicate a 'high-risk' pregnancy. This study focused on 378 patients with reported risk < or = 1:500 based on physician-supplied cGW (and hence considered at 'low risk' for Down's syndrome) to determine the effect of common 1-2-week dating errors on risk estimates. Using the original analytical data, each patient's risk was recalculated for each week over the 15-20 weeks, and classified into three categories: < 1:380 'low'; 1:380-1:100 'moderate'; and > 1:100 'high'. Advancing originally 'low-risk' patients by one week increased the risk by 1.09-14.1 times (median 3.18, mean 3.60); 46 (12.2%) became 'moderate' and 2 (0.5%) became 'high' risk. Advancing by two weeks increased risks 1.58-60.5 times (median 10.03, mean 12.04); 131 (36.5%) became 'moderate' and 39 (10.9%) became 'high' risk. Predictably, oNTD screening results also were affected. Although 1-2 week differences in AFP medians had little effect on most patients in this study sample, some who originally were oNTD negative became oNTD positive, whereas others who had been oNTD positive became screen negative. Thus, in many cases, a 1-2 week dating error may have only minimal effect on the estimated risks for chromosome or neural tube defects, but in other cases the effect of such an error would be significant.