BACKGROUND: Maternal serum triple marker screening has been covered by the medical insurance system in Korea since December 2004. The number of tests is on the increase, but an external quality control program and a basic survey have not been established yet. The aim of this study was to port the survey of prenatal screening tests. METHODS: Three different quality control specimens were prepared using the sera obtained from 100 women who were in the 15th to 20th week of pregnancy and visited Asan Medical Center during May 2005. We assumed that the three specimens belonged to the first day of 15 weeks, third day of 16 weeks, and second day of 19 weeks, respectively, and sent them to 10 laboratories. Nine laboratories replied to the survey. We analyzed concentrations, multiples of medians (MoMs), and risk estimates. RESULTS: The coefficients of variance of MoM were 32.1-32.6% for alpha-fetoprotein, 15.3-19.8% for unconjugated estriol, 6.3-12.5% for human chorionic gonadotropin, and 12.9-18.2% for inhibin-A. In Down syndrome risk estimation for specimen-2, six of the eight laboratories that used the triple test reported the screen positive, but two laboratories reported negative. Three of five laboratories using the quadruple test reported the screen positive, and two laboratories reported negative. In case of neural tube defect, all laboratories except one reported all specimens the screen negative. In case of Edward syndrome, all laboratories reported all specimens the screen negative. CONCLUSIONS: Since MoMs and risk estimates showed a wide variation among the participating laboratories in this survey, an external quality control and the standardization of the variables seemed warranted.
Biological Markers/*blood ; Female ; Humans ; Korea ; Pregnancy ; Prenatal Diagnosis/*standards

OBJECTIVE: To analyze the results of noninvasive prenatal screening (NIPS) for fetal chromosome aneuploidy in twin pregnancy. METHODS: A total of 2057 women with twin-pregnancy between 12-26 weeks were recruited from Women's Hospital, Zhejiang University School of Medicine, Hangzhou Municipal Women's Hospital and Jiaxing Maternal and Child Health Hospital during February 2015 to August 2018. The cell-free DNA was extracted from the peripheral blood sample for DNA library, and non-invasive prenatal testing (NIPT) was performed by high-throughput sequencing technique. The fetal karyotype analysis or neonatal karyotype analysis was performed in pregnant women with fetal chromosome aneuploidy, and all subjects were followed up. The efficiency of NIPS testing for twin aneuploidy was calculated. RESULTS: NIPS revealed chromosome abnormalities in 11 out of 2057 twin pregnant women, 9 cases were confirmed chromosome abnormalities, 2 cases were normal and no false negative cases. In this screening, the detection rate, sensitivity, specificity, positive predictive value, false positive rate of NIPS were 100.00%, 100.00%, 99.90%, 81.82%, 0.10%. Those were 100.00%, 100.00%, 99.95%, 87.50% and 0.05% for trisomy 21, 100.00%, 100.00%, 100.00%, 100.00%, 0.00% for trisomy18, and the specificity and false positive rate for trisomy13 were 99.95% and 0.05%, respectively. CONCLUSIONS NIPS can detect fetal chromosomal aneuploidy rapidly and accurately in twin pregnancies,and it is of value in clinical application.
Aneuploidy ; Female ; Humans ; Noninvasive Prenatal Testing ; standards ; Pregnancy ; Pregnancy, Twin ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Trisomy

OBJECTIVETo analyze the results of prenatal karyotype of the external quality assessment program in 2013 in order to provide references and recommendations for improving the capability and performances of karyotype analysis of prenatal screening laboratories.

METHODSFive lots of quality control cell photos were sent to 500 laboratories. The participants were asked to decide whether the photos have demonstrated any abnormal karyotype and determine the abnormal type. The results should be submitted before the deadline and compared with the standard results to evaluate the performances of the laboratory.

RESULTSOne hundred forty three laboratories have returned their karyotype results for the survey. The standard answers were 7,XX,+18, 46,X,i(X)(q10), 46,XY,i(21)(q10) or 46,XY,+21,der(21;21)(q10;q10), 46,XY and 47,XY,+21 in sequential order, which were used to estimate the score of each participant. The pass rates for five lots were 97.9%, 97.2%, 95.8%, 100.0% and 97.9%, respectively. The total pass rate was 97.7%. The error rates were 2.1%, 2.8%, 4.2%, 0 and 2.1%, respectively. The total error rate was 2.3%.

CONCLUSIONSome laboratories did not correctly identify the abnormal karyotypes, while some could not determine the right type of karyotype. The external quality assessment program of prenatal diagnosis of karyotype analysis should be conducted annually in order to improve the capability and performances of karyotype analysis of prenatal screening laboratories.

Adult ; Chromosomes, Human ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; methods ; standards ; Humans ; Karyotyping ; methods ; standards ; Male ; Pregnancy ; Prenatal Diagnosis ; methods ; standards ; Young Adult

To review the registration and technical data for prenatal diagnosis of chromosome aneuploidy by next generation sequencing technology. On the basis of introducing declarations of the reagents, analysis registration dossier common problems. And analysis the requirement of performance evaluation, reference intervals and clinical evaluation study.
Aneuploidy ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Prenatal Diagnosis ; standards

OBJECTIVETo develop a method for evaluating the feasibility of prenatal screening using local median value and determining the cut-off value.

METHODSWith receiver operating characteristic curve (ROC) analysis, results of second trimester prenatal screening calculated by a local median value in a new model and the built-in median value in 2T software were compared. The cut-off value was set by serial analysis of true and false positive rates and other relevant data.

RESULTSThe ROC curve has accurately estimated the difference in the screening efficacy between a local median value and that embedded in the 2T model, and established a reasonable cut-off value for the laboratory based on false positive rate and detection rate.

CONCLUSIONThe method of ROC curve can be used to evaluate the performance of local median value in prenatal screening and to test the rationality of cut-off value established in the laboratory. As the result, a better cut-off value may be derived.

China ; epidemiology ; Down Syndrome ; diagnosis ; epidemiology ; genetics ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Trimester, Second ; genetics ; Prenatal Diagnosis ; instrumentation ; methods ; standards ; ROC Curve ; Software

To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening.Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0.With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% (<0.05), in which the positive rate of Down syndrome decreased (<0.05), that of deformity of neural tube increased (<0.05), and that of trisomy 18 syndrome remained the same (>0.05). The median MoMs of free-hCG β and α-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all<0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0.BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.
Adult ; Body Weights and Measures ; standards ; Cephalometry ; standards ; statistics & numerical data ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; standards ; Chromosomes, Human, Pair 18 ; Down Syndrome ; diagnosis ; embryology ; Epidemiologic Measurements ; Female ; Fetal Development ; Gestational Age ; Head ; embryology ; Humans ; Mass Screening ; methods ; standards ; statistics & numerical data ; Menstrual Cycle ; Neural Tube Defects ; diagnosis ; embryology ; Pregnancy ; Prenatal Diagnosis ; methods ; standards ; statistics & numerical data ; Reference Values ; Trisomy ; diagnosis ; Trisomy 18 Syndrome ; alpha-Fetoproteins ; analysis ; standards

OBJECTIVE: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in prenatal genetic diagnosis for fetuses with absent nasal bone. METHODS: Seventy four fetuses with absent nasal bone detected by prenatal ultrasound scanning were recruited from Women's Hospital, Zhejiang University School of Medicine during June 2015 and October 2018. The chromosome karyotypes analysis and SNP array were performed. The correlation between absent fetal nasal bone and chromosome copy number variants was analyzed. RESULTS: Among 74 fetuses, 19 were detected to have chromosomal abnormalities, including 16 cases of trisomy-21, 1 case of trisomy-18 and two cases of micro-deletion/duplication. Among 46 cases with isolated absence of nasal bone, 3 had trisomy-21, and 1 had a micro-duplication. Absence of nasal bone in association with nuchal translucency thickening had a higher rate of abnormal karyotypes compared with isolated absence of nasal bone (=32.27,<0.01). CONCLUSIONS Fetuses with absent nasal bone and nuchal translucency thickening are likely to have chromosome abnormalities, and SNP array testing is recommended to exclude the chromosome abnormalities.
Chromosome Aberrations ; Female ; Fetus ; Humans ; Nasal Bone ; abnormalities ; Oligonucleotide Array Sequence Analysis ; standards ; Polymorphism, Single Nucleotide ; genetics ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; methods

Chorionic Gonadotropin, beta Subunit, Human ; blood ; Cost-Benefit Analysis ; Down Syndrome ; blood ; diagnosis ; False Positive Reactions ; Female ; Health Care Costs ; Humans ; Maternal Serum Screening Tests ; economics ; methods ; standards ; Pregnancy ; Pregnancy Trimester, First ; blood ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prenatal Care ; methods ; Prenatal Diagnosis ; economics ; methods ; standards