Prenatal diagnosis of neural tube defects. II. Analysis of false positive and false negative alpha-fetoprotein results.

Certain problems and pitfalls attend the use of the alpha-fetoprotein (AFP) assay for the prenatal diagnosis of neural tube defects (NTDs). Analysis of 2495 consecutive cases revealed 57 (2.3%) with amniotic fluid AFP levels greater than 3 SD above the mean. Fetal deaths (9), various fetal abnormalities, (7) and spontaneous abortions (4) occurred among this group. In addition, there were 30 cases with AFP levels greater than + 3 SD above the mean in which a normal child was delivered--a true false positive rate of 1.2%. To determine if the false positive rate could be diminished, 40 amniotic fluid samples with AFP greater than + 2 SD were subjected to further detailed analysis for fetal hemoglobin, total protein, and IgM concentrations. Even with this battery of tests, we estimate that between 1 and 2% of normal amniotic fluids have elevated AFP levels and either fall as expected outside the + 3 SD range, or have elevated AFP levels due to unknown causes.