Muller Françoise, Sault Corinne, Lemay Catherine, Roussel-Mizon Nathalie, Forestier François, Frendo Jean-Louis
Service de Biochimie, Hôpital Ambroise Paré, Boulogne, France.
Prenat Diagn. 2002 Jul;22(7):605-8. doi: 10.1002/pd.345.
Trisomy 21 maternal serum marker screening has led to screening for other anomalies, including trisomy 18. Trisomy 18 is generally prenatally diagnosed because of major morphological defects. However, in up to 30% of cases ultrasound signs are unclear, and in most cases diagnosis is performed late in pregnancy. Of the different maternal serum markers, PAPP-A is now considered as the best for trisomy 18 screening. However, pregnancy-associated plasma protein A (PAPP-A) is of value in first trimester screening for trisomy 21, but not in the second trimester. We therefore propose a two-step screening strategy. Based on 45 trisomy 18 cases, we confirm the values of alpha-fetoprotein (AFP) (median 0.61 MoM), free beta-human chorionic gonadotrophin (beta-hCG) (median 0.24 MoM) and of PAPP-A (median 0.08 MoM). In the first step, a 0.5 MoM cut-off for AFP or for free beta-hCG resulted in detection of 37/45 trisomy 18 cases (82%) with a 10% false-positive rate. The second step consisted of the measurement of PAPP-A for all these false-positive cases. Using a PAPP-A cut-off of 0.5 MoM, all the 37 trisomy 18 cases were detected, but now with a 0.1-0.2% false-positive rate. Amniocentesis was only offered to these few patients. This two-step second trimester screening will be of value for patients who have not been included in first trimester screening based on nuchal translucency (NT) measurement combined with the first trimester markers, PAPP-A and free beta-hCG.
21三体综合征的母体血清标志物筛查已促使对其他异常情况进行筛查，包括18三体综合征。18三体综合征通常因严重的形态学缺陷而在产前被诊断出来。然而，在高达30%的病例中，超声征象不明确，且在大多数情况下，诊断在妊娠晚期进行。在不同的母体血清标志物中，妊娠相关血浆蛋白A（PAPP-A）现在被认为是18三体综合征筛查的最佳标志物。然而，妊娠相关血浆蛋白A（PAPP-A）在孕早期筛查21三体综合征时有价值，但在孕中期则不然。因此，我们提出了一种两步筛查策略。基于45例18三体综合征病例，我们确定了甲胎蛋白（AFP）（中位数0.61 MoM）、游离β-人绒毛膜促性腺激素（β-hCG）（中位数0.24 MoM）和PAPP-A（中位数0.08 MoM）的值。第一步，AFP或游离β-hCG的截断值为0.5 MoM时，可检测出45例18三体综合征病例中的37例（82%），假阳性率为10%。第二步是对所有这些假阳性病例测量PAPP-A。使用PAPP-A截断值0.5 MoM时，所有37例18三体综合征病例均被检测出，但此时假阳性率为0.1 - 0.2%。仅对这少数患者进行羊膜穿刺术。对于那些未纳入基于颈部透明带（NT）测量结合孕早期标志物PAPP-A和游离β-hCG的孕早期筛查的患者，这种孕中期两步筛查将具有价值。
