AMNIOTIC-FLUID ALPHA-FETOPROTEIN MEASUREMENT IN ANTENATAL DIAGNOSIS OF ANENCEPHALY AND OPEN SPINA BIFIDA IN EARLY PREGNANCY: Second Report of the U.K. Collaborative Study on Alpha-fetoprotein in Relation to Neural-tube Defects

Abstract

Seventeen centres collaborated in a study to determine the efficiency of amniotic fluid alpha-fetoprotein (AFP) measurement as a method of diagnosis for fetal open neural-tube defects (NTDs) between 13 and 24 weeks of pregnancy. Data were collected on 13 105 singleton pregnancies without fetal NTDs and on 385 with fetal NTDs (222 with anencephaly, 152 with spina bifida of which 123 were known to have open lesions, and 11 with encephalocele). The percentage of unaffected pregnancies with amniotic-fluid AFP values equal to or greater than a given cut-off level (expressed as a multiple of the normal median) increased with gestational age, but similar percentages could be obtained by using different cut-off levels at different gestational ages such as 2·5 x median at 13-15 weeks, 3·0 at 16-18 weeks, 3·5 at 19-21 weeks, and 4·0 at 22-24 weeks. With these cut-off levels 98% (218/222) of cases of anencephaly and 98% (120/123) of cases of open spina bifida gave positive results, as did 0·48% (61/12 804) of unaffected singleton pregnancies not associated with miscarriage (excluding 7 positive results relating to cases of serious fetal malformation). Among pregnancies with clear amniotic-fluid samples (i.e., not visibly bloodstained) the detection-rates were the same (98% [134/137] and 98% [99/101] respectively), but the false-positive rate was much lower (0·27% [31/11 625]). In the United Kingdom as a whole the estimated approximate odds of having a fetus with open spina bifida, given a single positive amniotic-fluid AFP result, are