ObjectiveTo perform a cost-effectiveness analysis of various protocols used in the diagnostic evaluation of pregnancies complicated by elevated levels of maternal serum alpha-fetoprotein (MSAFP).MethodsThe variables incorporated in this model were the prevalence of relevant fetal anomalies; the sensitivity and specificity of MSAFP at 2.0 or 2.5 multiples of the median (MoM); and the sensitivity, specificity, cost, and safety of targeted ultrasound and amniocentesis. We expressed the cost-effectiveness of each strategy as the total cost of the diagnostic evaluation divided by the number of anomalous fetuses identified, yielding the cost per identified anomalous fetus.ResultsIn a hypothetical cohort of 100,000 singleton pregnancies, a strategy of targeted ultrasound for MSAFP of at least 2.0 MoM detected 90 of 110 structurally abnormal fetuses, without iatrogenic fetal loss, at a cost of $5700 per anomalous fetus. A strategy of amniocentesis with karyotype determination for MSAFP of at least 2.5 MoM detected 15 additional abnormal fetuses (87 structural abnormalities, ten autosomal aneuploidies, and eight sex chromosomal aneuploidies), with nine iatrogenic fetal losses, at an incremental cost of $46,100 per anomalous fetus.ConclusionThe increased cost and iatrogenic fetal loss rate may not justify the increased diagnostic yield of amniocentesis as compared with ultrasound in the evaluation of pregnancies complicated by elevated MSAFP.