OBJECTIVE: To analyze the clinical data and results of prenatal diagnosis for fetuses with high-risk for trisomy/monosomy 13 by non-invasive prenatal testing (NIPT). METHODS: Clinical data of pregnant women with fetus at a high risk for trisomy/monosomy 13 by NIPT at the First Affiliated Hospital of Zhengzhou University from May 2016 to May 2024 were reviewed, and relevant data such as Z-score, positive predictive value (PPV) and fetal fraction (FF) were analyzed to assess the correlation between them. This study was approved by the Ethics Committee of the Hospital (No. 2018-YB-08). RESULTS: 71 fetuses were found to have a high risk by NIPT, including 58 cases for trisomy 13 (T13) and 13 cases for monosomy 13 (M13). 52 women had opted invasive prenatal diagnosis and 13 cases were confirmed, which yielded a positive prediction value (PPV) of 25%. 12 fetuses were confirmed as T13 (PPV = 29.3%; 12/41), 1 was confirmed as M13 (PPV = 9.1%; 1/11). The PPV had increased along with the Z-score. Fetal faction (FF) was not correlated with the age of woman but gestational age, and was negatively correlated with the body mass index. No statistical difference was found in FF and Z-score between true- and false-positive fetuses, and there was a weak correlation between the Z-score and FF. The PPV of the NIPT could be improved by combining the results of ultrasonography. CONCLUSION The high false positive rate for T13 may be related to confined placental mosaicism, PPV is related to the Z-score, which in turn is related to FF. High-risk women are strongly recommended to undergo genetic counseling and prenatal diagnosis. Clinicians should consider relevant information such as the age of women, gestational age, indication for prenatal screening, Z-score, PPV, and FF in order to accurately interpret the result of NIPT, reduce anxiety, and avoid direct termination of the pregnancy.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods*

OBJECTIVE: To assess the clinical value of digital PCR (dPCR) for the prenatal diagnosis of common fetal aneuploidies. METHODS: A dPCR-based assay was developed for detecting trisomies 21, 18, and 13. A retrospective analysis was carried out on 173 amniotic fluid samples collected by the Prenatal Diagnosis Center of Taizhou Hospital between January 2017 and December 2023. By using chromosomal karyotyping as the gold standard, the diagnostic performance of the multiplex dPCR system was evaluated in a double-blind manner. This study has been approved by the Ethics Committee of Taizhou Hospital (Ethics No. K20250339). RESULTS: Chromosomal karyotyping has identified 59 cases of trisomy 21, 5 cases of trisomy 18, 2 cases of trisomy 13, 6 cases with chromosomal structural abnormalities or mosaicisms, and 101 cases with a normal karyotype. The dPCR results (Z-score cutoff = 4.0, CI = 99.997%) showed full concordance with karyotyping (sensitivity = 100%, specificity = 100%, Kappa = 1). Among the 6 structurally abnormal or mosaicism samples, dPCR has accurately detected 4 cases, but mis-classified 2 cases of trisomy 21 with very low-level mosaicisms (3.3%, 6.9%, respectively) as normal. CONCLUSION The established multiplex dPCR system demonstrated high diagnostic accuracy for common chromosomal aneuploidies, with results available within 24 hours. It can serve as an efficient supplementary tool to conventional chromosomal karyotyping, providing reliable support for time-sensitive clinical decision-making in prenatal diagnosis.
Humans ; Female ; Pregnancy ; Aneuploidy ; Prenatal Diagnosis/methods* ; Karyotyping ; Retrospective Studies ; Polymerase Chain Reaction/methods* ; Chromosome Disorders/genetics* ; Adult ; Trisomy 13 Syndrome/diagnosis* ; Trisomy 18 Syndrome/genetics* ; Down Syndrome/genetics*

OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; DNA Copy Number Variations ; Placenta ; Chromosomes, Human, Pair 1 ; In Situ Hybridization, Fluorescence ; Prenatal Diagnosis/methods* ; Fetus ; Amniotic Fluid ; Chromosome Aberrations ; Trisomy/genetics*

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.
Child ; Female ; Pregnancy ; Humans ; Retrospective Studies ; Cell-Free Nucleic Acids ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Sex Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Trisomy 13 Syndrome/diagnosis* ; Aneuploidy ; DNA/genetics* ; Trisomy/genetics*

OBJECTIVE: To analyze the Z values of true and false positive cases by non-invasive prenatal testing (NIPT) in order to improve its accuracy in clinical practice. METHODS: Results of 24 384 NIPT tests were reviewed. For cases with high risks for trisomies 21, 18 and 13, the range of Z values in true and false positive cases was analyzed and discussed. RESULTS: A total of 335 high-risk cases were identified by NIPT, among which 256 had elected prenatal diagnosis, 153 (59.77%) were verified as true positives, and 103 (40.23%) were false positives, and the area under the curve (AUC) was 0.9994. For NIPT screening, the positive predictive value (PPV) for trisomy 21 was 100% when Z>13, regardless if the pregnant woman was over 35. When 313, the PPV for trisomy 21 was 80% (8/10) for those>35 and about 41.6% (5/12) for those<35. For trisomy 18, the PPV was 100% when Z>13, and only 14.3% (1/7) when 313. NIPT showed that the positive predictive value of trisomy 13 was only 6.67% (1/15) when the trisomy 13 Z value was more than 20, the positive predictive value was 100% , and the trisomy 13 Z value was 3CONCLUSION NIPT is a technique similar to prenatal diagnosis and has a high positive predictive value for trisomies 18 and 21. Proper classification and division of the high-risk Z value of NIPT can further improve the positive predictive values for trisomies 21, 18 and 13 in different intervals, and is more helpful to guide clinicians in genetic counseling for high-risk pregnant women. Meanwhile, the compliance of prenatal diagnosis in high risk NIPT pregnant women with Z value between 3~13 was improved.
Female ; Pregnancy ; Humans ; Trisomy 13 Syndrome/genetics* ; Trisomy/genetics* ; Down Syndrome/genetics* ; Chromosome Disorders/genetics* ; Trisomy 18 Syndrome/diagnosis* ; Prenatal Diagnosis/methods*

OBJECTIVE: To evaluate the efficacy of non-invasive prenatal testing (NIPT) in the prenatal screening and its role in the system of prenatal diagnosis. METHODS: A total of 22 649 singleton pregnant women who were registered and finally delivered or had induced labor at Beijing Obstetrics and Gynecology Hospital of Capital Medical University were enrolled. The routes of prenatal screening were analyzed to evaluate the efficacy of prenatal screening. Meanwhile, 9268 pregnant women who underwent invasive prenatal diagnosis procedure were enrolled. The indications and results of prenatal diagnosis were analyzed to evaluate the effectiveness of prenatal screening. RESULTS: 60.24% of singleton pregnant women have opted for Down syndrome screening, and their age was mainly under 35. The proportion of women opted for NIPT was 34.74%, and were mainly between 35 and 39. The overall diagnostic rate of trisomy 21, 18 and 13 trisomy for those with high risk by NIPT was 0.89%, which yielded a positive predictive value of 75.71%. For those with moderate risk by serum screening, 0.30% was predicted with a high risk by NIPT. Among women undergoing prenatal diagnosis, 63.04% and 21.22% had the indication of advanced age or high risk by serum screening, and the positive predictive values were 5.1% and 5.13%, respectively. By contrast, 2.30% of women undergoing prenatal diagnosis had a high risk by NIPT, which yielded a positive predictive value of 54.46%. CONCLUSION With the change of the age composition of pregnant women and increase in the complexity of pregnancy in China, to build a prenatal screening system based on NIPT will be helpful to improve the efficiency of the current system of prenatal screening and diagnosis.
China ; Down Syndrome/genetics* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome ; Trisomy 18 Syndrome

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.
Female ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome/genetics* ; Trisomy 18 Syndrome

OBJECTIVETo diagnose a neonate presenting with multiple dysmorphic features, Cri-du-chat signs and hypoglycemia and to correlate the phenotype with the genotype.

METHODSThe patient was diagnosed with conventional cytogenetics and real-time fluorescence quantitative PCR (QF-PCR). The phenotype was then correlated with the genotype through a review of literature.

RESULTSThe neonate was diagnosed with a partial 13q trisomy (q12 → qter) and partial 5p monosomy (p15 →pter).

CONCLUSIONA rare diagnosis has been established with combined cytogenetic and molecular genetic techniques. QF-PCR has a broad application in genetic diagnosis.

Chromosomes, Human, Pair 13 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Cri-du-Chat Syndrome ; diagnosis ; genetics ; Cytogenetics ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; diagnosis ; genetics ; Male ; Trisomy ; diagnosis ; genetics

OBJECTIVETo evaluate the feasibility of using fluorescence in situ hybridization(FISH) for the detection of a few common chromosome aneuploidies on interphase nuclei of uncultured amniotic fluid cells.

METHODSAmniotic fluid samples were taken from 55 women at 16-32 weeks of pregnancy; interphase FISH was performed for diagnosing Down syndrome and aneuploidies of other four chromosomes 13, 18, X and Y. Then the karyotypes from standard cytogenetic analysis after percutaneous umbilical blood sampling(PUBS) were compared to the FISH results.

RESULTSEach of the 55 uncultured amniotic fluid samples tested with FISH was enumerated 200 nuclei. Fifty-three samples were normal. Two samples were found to have trisomy 21(one is a case of standard trisomy 21 with three signals in all 200 nuclei, the other is a mosaic trisomy 21).

CONCLUSIONInterphase FISH analysis of uncultured amniotic fluid cells is a rapid, accurate and very sensitive method. It could be used in the prenatal cytogenetic laboratory.

Adult ; Amniocentesis ; Amniotic Fluid ; cytology ; Aneuploidy ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, X ; Chromosomes, Human, Y ; Down Syndrome ; diagnosis ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Pregnancy ; Prenatal Diagnosis ; methods ; Trisomy