D'Alton M E, Malone F D, Chelmow D, Ward B E, Bianchi D W
Department of Obstetrics and Gynecology, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111, USA.
Am J Obstet Gynecol. 1997 Apr;176(4):769-74; discussion 774-6. doi: 10.1016/s0002-9378(97)70600-8.
This study examines the role of fluorescence in situ hybridization on uncultured amniocytes for prenatal diagnosis in a population at high risk for aneuploidies.
All patients undergoing amniocentesis for fetal structural abnormality on ultrasonographic examination (performed from 13 to 39 weeks), abnormal maternal serum aneuploidy screening results, or advanced maternal age with substantial parental anxiety were offered both fluorescence in situ hybridization on uncultured cells and conventional metaphase karyotyping on dividing cells.
From 1992 to 1995, 315 patients were studied. Mean time to obtain results was 2.8 days for fluorescence in situ hybridization and 8.3 days for karyotype. Fluorescence in situ hybridization was informative in 254 samples (80.6%), and within this group 21 aneuploidies were correctly identified. Among informative specimens there was 100% sensitivity and specificity, with 100% positive and negative predictive values. Of the 315 samples, 61 (19.4%) were uninformative or unreportable. Of 25 total cases of karyotype-proved aneuploidy, 4 were reported as uninformative by fluorescence in situ hybridization, for a total detection rate of 84%. Overall, amniocenteses performed after 24 weeks were significantly more likely to be uninformative than those performed in the second trimester (45% vs 16%, p = 0.01), peaking at a 56% uninformative rate after 33 weeks. Logistic regression analysis showed an 8% increase in the uninformative rate per week of gestational age (odds ratio 1.08, 95% confidence interval 1.04 to 1.14).
Fluorescence in situ hybridization on uncultured amniocytes is a rapid, clinically useful tool for prenatal diagnosis, with informative specimens being highly accurate. The combination of a structural fetal anomaly and an abnormal fluorescence in situ hybridization result should allow for definitive management decisions. The significant increase in uninformative specimens at later gestational ages limits its usefulness in the third trimester.
本研究探讨荧光原位杂交技术在未经培养的羊水中的应用，用于高危人群非整倍体的产前诊断。
所有因超声检查发现胎儿结构异常（孕13至39周进行）、孕妇血清非整倍体筛查结果异常或孕妇年龄较大且父母焦虑严重而接受羊膜腔穿刺术的患者，均接受未经培养细胞的荧光原位杂交和分裂细胞的传统中期核型分析。
1992年至1995年，共研究了315例患者。荧光原位杂交获得结果的平均时间为2.8天，核型分析为8.3天。荧光原位杂交在254个样本中提供了信息（80.6%），在该组中正确识别出21例非整倍体。在提供信息的标本中，敏感性和特异性均为100%，阳性和阴性预测值均为100%。在315个样本中，61个（19.4%）未提供信息或无法报告。在25例经核型分析证实的非整倍体病例中，4例荧光原位杂交报告为未提供信息，总检出率为84%。总体而言，孕24周后进行的羊膜腔穿刺术比孕中期进行的更有可能未提供信息（45%对16%，p = 0.01），在孕33周后未提供信息率达到峰值56%。逻辑回归分析显示，孕周每增加一周，未提供信息率增加8%（优势比1.08，95%置信区间1.04至1.14）。
未经培养的羊水细胞荧光原位杂交是一种快速、临床有用的产前诊断工具，提供信息的标本高度准确。胎儿结构异常与荧光原位杂交结果异常相结合应有助于做出明确的管理决策。孕晚期未提供信息标本的显著增加限制了其在孕晚期的应用。
