Cut-off levels for maternal plasma alpha-fetoprotein in the diagnosis of neural tube defects: validation of the use of multiples of the normal median.

A retrospective study was made of measurement of maternal plasma alpha-feto-protein (AFP) by a standard radioimmunoassay technique, as a method of screening for neural tube defects (NTDs) between 15 and 20 weeks gestation. There was a good fit of a log-normal distribution to the data at each week and multiples of the normal median were equivalent to constant centiles over weeks 15 to 20 and possibly at later weeks also. There were 700 plasma samples from women with normal prenancies and 60 from women with pregnancies complicated by fetal NTDs (30 with anencephaly and 30 with spina bifida). At 15 to 20 weeks of pregnancy, 90 per cent of women with fetuses affected by anencephaly, 70 per cent of those with fetuses affected by open spina bifida and 3 per cent ofthose with normal pregnancies had plasma AFP levels at or above 2.4 times the normal median for each gestational week. It was estimated that 2.1, 2.4 and 3.1 times the normal median maternal plasma AFP levels were equivalent to the 95th, 97th and 99th centiles respectively. The interassay coefficients of variation estimated on control sera throughout the entire study were 4 to 6 per cent.