Wald N J, Cuckle H, Brock J H, Peto R, Polani P E, Woodford F P
Lancet. 1977 Jun 25;1(8026):1323-32.
Nineteen centres collaborated in a study to determine the efficiency of maternal serum-alpha-fetoprotein (A.F.P.) measurement as a method of screening for neural-tube defects (N.T.D.S.) between 10 and 24 weeks of pregnancy. Data were collected on 18 684 singleton pregnancies and 163 twin pregnancies without fetal N.T.D.s, and on 301 singleton pregnancies with fetal N.T.D.s (146 with anencephaly, 142 with spina bifida, and 13 with encephalocele). The best time for detecting open spina bifida by measuring maternal serum-A.F.P. is at 16-18 weeks of pregnancy. In clinical practice, serum-A.F.P. cut-off levels expressed as multiples of the normal median may be more convenient to use than percentiles because they are easier to derive and more stable. Also, the proportion of affected pregnancies with serum-A.F.P. levels exceeding a given multiple of the median is unlikely to vary significantly from centre to centre or over time. In contrast, the proportion of unaffected pregnancies with A.F.P. levels exceeding a given multiple of the normal median will vary depending on the precision with which serum-A.F.P. and gestation are measured. At 16-18 weeks of pregnancy 88% of cases of anencephaly, 79% of cases of open spina bifida, and 3% of unaffected singleton pregnancies had A.F.P. levels equal to or greater than 2-5 times the median for unaffected singleton pregnancies. At this gestation age the numbers of unaffected pregnancies with A.F.P. levels above 2-5 times the normal median can be reduced by about a third if women with borderline A.F.P. levels are retested, although this would not greatly change the detection-rate of affected pregnancies. In the United Kingdom as a whole, women with serum-A.F.P. levels above 2-5 times the normal median at 16-18 weeks of gestation will have an approximately 1-in-20 chance of having a fetus with open spina bifida; the risk of having any N.T.D. will be approximately 1 in 10. The results of this study indicate that screening pregnant women by measuring the concentration of A.F.P. in their serum is an effective method of selecting women for ultrasonography and amniocentesis so that N.T.D.s can be diagnosed in utero.
19个中心合作开展了一项研究，以确定在妊娠10至24周期间测量母血清甲胎蛋白（A.F.P.）作为筛查神经管缺陷（N.T.D.S.）方法的有效性。收集了18684例单胎妊娠和163例无胎儿神经管缺陷的双胎妊娠的数据，以及301例有胎儿神经管缺陷的单胎妊娠的数据（146例无脑儿、142例脊柱裂和13例脑膨出）。通过测量母血清A.F.P.检测开放性脊柱裂的最佳时间是妊娠16至18周。在临床实践中，以正常中位数倍数表示的血清A.F.P.临界值水平可能比百分位数更便于使用，因为它们更容易得出且更稳定。此外，血清A.F.P.水平超过中位数给定倍数的受影响妊娠比例在不同中心之间或随时间不太可能有显著差异。相比之下，如果血清A.F.P.和孕周测量的精确度不同，A.F.P.水平超过正常中位数给定倍数的未受影响妊娠比例会有所变化。在妊娠16至18周时，88%的无脑儿病例、79%的开放性脊柱裂病例以及3%的未受影响单胎妊娠的A.F.P.水平等于或大于未受影响单胎妊娠中位数的2.5倍。在这个孕周，如果对A.F.P.水平处于临界值的女性进行重新检测，A.F.P.水平高于正常中位数2.5倍的未受影响妊娠数量可减少约三分之一，不过这不会大幅改变受影响妊娠的检出率。在英国总体上，妊娠16至18周时血清A.F.P.水平高于正常中位数2.5倍的女性怀有开放性脊柱裂胎儿的几率约为二十分之一；怀有任何神经管缺陷胎儿的风险约为十分之一。这项研究结果表明，通过测量孕妇血清中A.F.P.浓度来筛查孕妇是为超声检查和羊膜穿刺术选择女性的有效方法，以便能在子宫内诊断神经管缺陷。
