ABSTRACT
Objective To evaluate the value of non-invasive prenatal testing (NIPT) as first-trimester screen (FTS) for the detection of trisomies 21, 18 and 13. Methods This was a retrospective study. 8517 pregnancies who performed NIPT at Obstetrics and Gynecology Hospital of Fudan University from 2017 May to 2018 June. 14 cases (0.16％) were failed. 8503 pregnancies were divided into 2 groups:NIPT joint traditional screening, NIPT. High risk pregnancies were verified by prenatal diagnosis. Evaluate the performance of NIPT. All pregnancies were followed up. Frequencies were compared with Fisher′s exact test. Results 8517 pregnancies underwent NIPT. 14 cases (0.16％) were failed. 83 cases of remaining 8503 cases had high risk results, among which 29 were trisomy 21, 14 were trisomy 18, 6 were trisomy 13 and 34 were sex chromosome aneuploidies (SCA). In 2996 cases who underwent NIPT joint traditional screening, NIPT found 14 cases of common aneuploidies 12 cases of SCA. 11 and 3 cases were validated by invasive prenatal diagnosis, respectively. In 5507 NIPT cases, 35 cases of common aneuploidies and 22 cases of SCA were found, among which 29 and 11 cases were validated. There was no significant differences between two groups for common aneuploidies (P=1.00). The sensitivity were 11/11 and 29/29 respectively,the specificity were 99.90％(2982/2985) and 99.89％(5472/5478), the positive predictive value (PPV) were 78.57％(11/14) and 82.86％(29/35), the negative predictive value (NPV) were 100％(2982/2982) and 100％ (5472/5472), respectively. Besides, the sensitivity and PPV of NIPT for SCA were 100％ and 41.18％. No false negative was found. Conclusions The proportion of pregnancies underwent NIPT alone was 64.77％. NIPT had excellent performance (the specificity and PPV) for common aneuploidies, and also had a certain value for SCA, which greatly reduced in invasive diagnosis. NIPT is a commendable essay as a first-line prenatal screening. Invasive diagnosis is still necessary for pregnancies with high-risk of NIPT.
ABSTRACT
Objective To explore the clinical significance of non-invasive prenatal genetic testing to screen prenatal fetal chromosomal abnormalities. Methods Peripheral blood was collected from 6 283 pregnant women who underwent non-invasive prenatal genetic testing at our hospital, and fetal DNA was extracted and purified for analysis. The complementary base principle of semiconductor chip technology was used to analyze all sequenced signals with BioelectronSeq 4000. Invasive prenatal diagnosis was performed in high-risk pregnant women according to the results of the sex chromosome sequencing signal analysis. Results Of the 6 283 pregnant women screened, 14 were found to have chromosomal abnormalities, and the positive rate was 0. 22％. Karyotype analysis was performed on 11 of the women; the remaining 3 refused to be diagnosed. Of these 11 women, 2 of the 5 patients with a high risk of XO were diagnosed with fetal chromosomal abnormalities (diagnosed as XO/XXX chimera and XO, respectively), and 3 were diagnosed with a normal karyotype; 5 patients with a high risk of XXY were diagnosed as XXY; and 1 patient with a high risk of XXX was confirmed as XXX. NIPT accuracy was measured to be 73％ (8/11). The detection rate of fetal chromosomal abnormalities by non-invasive prenatal genetic testing was significantly higher in the years 2015-2016 than in 2011-2014 (P ＜ 0. 05). Conclusion Non-invasive prenatal genetic testing for screening chromosomal abnormalities has a high accuracy rate and could improve the detection rate of fetal chromosomal abnormalities.
ABSTRACT
More than 6,000 rare disorders including genetic diseases have been reported. Of them, 1,500 diseases (1,211 for clinical diagnosis and 289 for research only) are technically possible for genetic testing. In Korea, since 2005, only 63 genetic diseases is permitted for prenatal genetic testing by the "Bioethics and Biosafety Law". The article 25 in the law prescribes 63 genetic diseases without clear indication for its selection and inclusion criteria. In EU, USA, and other foreign countries, however, there is no provision in the statute on prenatal genetic testing; it is not restricted by a law. Recently, a woman (Mrs. L, 38y) who is a carrier for Menkes disease made an appeal to a government for an amendment of the "Bioethics and Biosafety Law" prohibiting the prenatal diagnosis of her pregnancy at risk for Menkes disease. Menkes disease (MNK) is an X-linked recessive disorder characterized by neurodegeneration, connective tissue defects and hair abnormalities, and no effective treatment is available yet. The prevalence rate of MNK is one in about 250,000 live births. Menkes syndrome patients fail to absorb copper from the gastrointestinal tract in quantities adequate for meeting nutritional needs. These needs seem particularly acute during the initial 12 month of life, when the velocity of brain growth and motor neurodevelopment. Most of pts. die around 3yrs. of age. Mrs. L had a boy with Menkes disease who died at 2y.o. in 2001. Subsequent pregnancy in 2003, she was able to have prenatal genetic testing for mutation of the Menkes (ATP7A) gene and delivered a healthy baby boy. Now, She is pregnant again and wants to have prenatal diagnosis. however, this time, she was not allowed to have any more because Menkes disease is not included in 63 genetic diseases permitted by the law for prenatal genetic testing, in spite of the fact that she is a Menkes disease carrier and her pregnancy is at risk to have an affected baby. This case shows the practical problem of the legal restriction for prenatal genetic testing in Korea. In this study, we report a arguable case and discuss the controversial issues in the legal restriction for prenatal genetic testing in Korea.