Assay precision of serum α fetoprotein in antenatal screening for neural tube defects and Down's syndrome

Objectives To assess the impact of current serum α fetoprotein (AFP) assays on the performance of screening for open neural tube defects and Down's syndrome. Methods Maternal serum samples, collected between weeks 15 and 22 from 470 singleton pregnancies without neural tube defects or Down's syndrome, were assayed for AFP using an automated fluorometric immunoassay. The samples had been assayed for AFP using an in house radioimmunoassay with a lower precision ten years before. The variance of AFP using the radioimmunoassay was compared with that using the current fluorometric assay and then used to estimate the detection rates and false positive rates for neural tube defect and Down's syndrome screening. Results Current serum AFP assays are more precise. Using a cut off level of 2.5 multiples of the median, the false positive rate in screening for anencephaly and open spina bifida was 0.8% with the new assay compared with 2% using the previous assay. When screening for Down's syndrome, the false positive rate is reduced by about one percentage point without loss of detection. Conclusion Improvements in the precision of maternal serum AFP measurement have led to small but useful improvements in screening for open neural tube defects and Down's syndrome. Published estimates of screening performance using such modern assays can be revised accordingly.