Significance of elevated mid-trimester maternal plasma-alpha-fetoprotein values.

In a prospective trial of 15,481 pregnancies, 667 women (4.3%) had two sequential mid-trimester plasma-alpha-fetoprotein (A.F.P.) values above 2 times the median. The outcome of these pregnancies was open neural-tube defect (12.4%), birthweight less than 2.5 kg (10.3%), twins (9.8%), fetal wastage (9.5%), perinatal death (2.6%), other (1.3%), and "normal" singleton (54.1%). At higher A.F.P. cutoffs the proportion of "normal" singleton pregnancies declined rapidly, being 19% at 3 times the median and 9% at 4 times the median. If it is assumed that ultrasonography and amniotic-fluid A.F.P. assay can detect twins and most cases of neural-tube defect, the outcome of the residual pregnancies is still strongly influenced by plasma-A.F.P. level. Thus at a cut-off of 4 times the median two-thirds of the pregnancies in this residual group will end in spontaneous abortion, stillbirth, or neonatal death. It is suggested that counselling of women taking part in A.F.P. screening programmes should be strongly influenced by maternal plasma-A.F.P. levels, even if ultrasonographic findings and amniotic-fluid levels are normal.