Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Czeizel Institute, Budapest, Hungary.
PLoS One. 2024 Nov 5;19(11):e0308008. doi: 10.1371/journal.pone.0308008. eCollection 2024.
Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not only for common autosomal aneuploidies but also for rare autosomal trisomies (RATs) and structural chromosomal abnormalities (StrCAs). Due to their rarity, there is currently insufficient information on positive predictive value PPV of RAT and StrCA-positive cases in the literature. In this study, the screening accuracy and pregnancy outcomes of cases positive for rare chromosomal abnormalities were examined based on publications in which GW-NIPT testing was performed. True positive cases were determined using two different methodologies. One was a confirmed methodology, where only cases validated by genetic testing were considered true positives with a definite diagnosis, and the other was an extended methodology, where, in addition to cases confirmed by genetic testing, intrauterine fetal death and termination of pregnancy due to an abnormality confirmed by ultrasound examination were also considered true positives, where no diagnosis had been made but the fetus was probably affected. Seventeen studies were analyzed, with a total GW-NIPT population of 740,076. Of these, 1,738 were RAT positive. Using the confirmed method, we found the highest rates of true positives in T16, followed by T22, and T2, using the extended method, the highest rate of true positives in T15, T16 and T22. This is the first meta-analysis to determine the frequency of rare chromosomal abnormalities, test-positive rates, and the PPV of each chromosomal abnormality with high precision. Our results could aid pre- and post-test genetic counselling and help patients and clinicians in their decision-making.
全基因组非侵入性产前检测（GW-NIPT）不仅可以提供常见常染色体非整倍体的阳性结果，还可以提供罕见常染色体三体（RAT）和结构性染色体异常（StrCA）的阳性结果。由于它们的罕见性，目前文献中关于 RAT 和 StrCA 阳性病例的阳性预测值（PPV）的信息还不够充分。在这项研究中，根据进行 GW-NIPT 检测的出版物，检查了罕见染色体异常阳性病例的筛查准确性和妊娠结局。使用两种不同的方法学确定了真正的阳性病例。一种是确认方法，只有经过基因检测验证的病例才被认为是具有明确诊断的真正阳性病例，另一种是扩展方法，除了经过基因检测确认的病例外，还将因超声检查确认的异常而导致的宫内胎儿死亡和终止妊娠的病例也视为真正的阳性病例，尽管没有做出诊断，但胎儿可能受到了影响。分析了 17 项研究，总 GW-NIPT 人群为 740,076 例。其中 1738 例为 RAT 阳性。使用确认方法，我们发现 T16 的真正阳性率最高，其次是 T22 和 T2，使用扩展方法，T15、T16 和 T22 的真正阳性率最高。这是第一项使用高精度确定罕见染色体异常频率、阳性检出率和每种染色体异常的阳性预测值的荟萃分析。我们的结果可以为产前和产后遗传咨询提供帮助，并帮助患者和临床医生做出决策。
