Haddow J E, Palomaki G E, Knight G J, Williams J, Miller W A, Johnson A
Foundation for Blood Research, Scarborough, ME 04070-0190, USA.
N Engl J Med. 1998 Apr 2;338(14):955-61. doi: 10.1056/NEJM199804023381404.
Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester.
We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome.
A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations.
Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.
目前，孕期常规在孕中期对孕妇血清进行筛查以识别唐氏综合征胎儿。孕早期也可通过血清检测或超声测量单独或联合进行产前筛查。
我们对4412名孕妇（其中82%年龄在35岁及以上）进行了血清甲胎蛋白、非结合雌三醇、人绒毛膜促性腺激素（hCG）、hCG游离β亚基及妊娠相关蛋白A的检测，这些孕妇在妊娠9至15周时前往16个产前诊断中心进行绒毛取样或早期羊膜腔穿刺术。还报告了胎儿颈部透明带的超声测量结果。对所有妊娠进行了胎儿染色体分析。共有61例胎儿患有唐氏综合征。
在妊娠14周前共识别出48例受唐氏综合征影响的妊娠和3169例未受影响的妊娠；五种血清标志物对唐氏综合征的检出率如下：甲胎蛋白为17%，非结合雌三醇为4%，hCG为29%，hCG游离β亚基为25%，妊娠相关蛋白A为42%，假阳性率为5%。血清hCG及其游离β亚基的测量结果高度相关。当与妊娠相关蛋白A的血清浓度及孕妇年龄联合使用时，hCG的检出率为63%（95%可信区间为47%至76%），其游离β亚基的检出率为60%（95%可信区间为45%至74%）。各中心之间胎儿颈部透明带的测量结果差异很大，无法可靠地纳入我们的计算。
孕早期利用孕妇血清中妊娠相关蛋白A以及hCG或其游离β亚基进行检测，对唐氏综合征进行筛查是可行的。
