Fetal Medicine Unit, Department of Obstetrics, Aarhus University Hospital, Aarhus, Denmark.
Ultrasound Obstet Gynecol. 2014 Mar;43(3):265-71. doi: 10.1002/uog.13270. Epub 2014 Feb 25.
Targeted non-invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT.
This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype.
cFTS was completed in 193638 pregnancies. 10205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (<0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A<0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%.
A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT.
针对 21 三体、18 三体和 13 三体以及性染色体非整倍体的靶向非侵入性产前检测（NIPT）可能是传统核型分析的替代方法。本研究旨在确定 NIPT 漏诊其他具有明显表型意义的异常核型的风险。
这是一项在丹麦进行的为期 4 年的所有单胎妊娠接受联合早孕期筛查（cFTS）的回顾性基于人群的分析。从丹麦胎儿医学数据库中收集了有关孕产妇人口统计学、cFTS 和产前或产后核型的数据。核型根据是否可以通过 NIPT 检测到染色体异常以及是否可能影响表型进行分类。
cFTS 在 193638 例妊娠中完成。10205 例（5.3%）进行了细胞遗传学或分子分析。其中，1122 例（11.0%）核型异常，262 例（23.4%）漏诊，NIPT 但可能具有临床意义。在年龄超过 45 岁的女性、颈后透明带（NT）厚度增加（≥3.5 毫米）、游离β-人绒毛膜促性腺激素水平异常（<0.2 或≥5.0 中位数倍数（MoM））或妊娠相关血浆蛋白-A<0.2 MoM 的孕妇中，这种“非典型异常核型”的患病率增加。这些因素中的一种或多种在 3%的女性中存在，高危人群中非典型异常核型的患病率为 1.6%。
靶向 NIPT 会漏诊相当一部分核型异常。高龄产妇，或胎儿 NT 增加或生化异常，胎儿受非典型异常核型影响的风险较高，在考虑 NIPT 时需要相应咨询。
