Indications for prenatal diagnosis and pregnancy outcomes of Turner syndrome with different karyotypes in 205 cases / 中华围产医学杂志

Objective:To investigate the indications for prenatal diagnosis and pregnancy outcomes of fetal Turner syndrome (TS) with different karyotypes.Methods:Clinical data of TS cases diagnosed by fetal karyotyping in the Prenatal Diagnostic Center of Guangzhou Women and Children′s Medical Center from January 1, 2010, to June 30, 2021, were analyzed retrospectively. According to the karyotyping results, these cases were divided into two groups: monosomy X (45,X) and non-monosomy X groups (including karyotypes of mosaic monosomy X, isochromosome X, X deletion, X rearrangement, pseudodicentric X, and mosaicism with Y or Y deletion). Chi-square test was used to compare the detection rate, indications for prenatal diagnosis, and pregnancy outcomes of the two groups, and the Bonferroni test was conducted for further pairwise comparisons between the subgroups. The Chi-square test (or Fisher's exact test) was used to compare the abnormal ultrasound signs. Mann-Whitney U test was used to compare the nuchal translucency (NT) thickness of the two groups. Results:(1) Invasive prenatal diagnosis was performed on 27 981 pregnancies, and 205 (0.73%) of them were diagnosed with TS, including 135 cases of monosomy X and 70 cases of non-monosomy X (44 with numerical sex chromosome abnormalities, and 26 with structural sex chromosome abnormalities). (2) Out of the 205 pregnancies, 164 (80.0%) had one indication for prenatal diagnosis, and 41 (20.0%) had multiple indications. The detection rate of fetal ultrasonographic abnormalities [85.2% (115/135)] in monosomy X cases was significantly higher than that of three other indications [positive serological screening for Down's syndrome: 67.3% (35/52); positive non-invasive prenatal testing (NIPT) for sex chromosome abnormality: 60.0% (15/25); and other indications (advanced maternal age, adverse pregnancy history and thalassemia genes carried by both parents): 5.2% (7/135); all P<0.05], and also higher than the figure in non-monosomy X cases [25.7% (18/70), χ 2=71.55, P<0.001]. In non-monosomy X cases, the detection rates of TS among cases with high-risk results from serological screening for Down's syndrome and NIPT for sex chromosome abnormality [54.7% (29/53) and 68.3% (28/41)] were higher than those of the other two indications [fetal ultrasonographic abnormalities: 25.7% (18/70), other indications: 14.3% (10/70); all P<0.05]. (3) Of the 133 pregnancies with fetal ultrasonographic abnormalities as the indication, 65 (48.9%) had one abnormal ultrasound sign, and 68 (51.1%) had multiple signs. Among the 95 cases with ultrasound abnormalities in the first trimester and 38 cases in the second or third trimester, the incidence of cystic hygroma and hydrops was significantly higher in monosomy X cases than in non-monosomy X cases [in the first trimester: 71.8% (61/85) vs 1/10, 34.1% (29/85) vs 0/10; in the second or third trimester: 73.3% (22/30) vs 0/8, 50.0% (15/30) vs 0/8; Fisher's exact test, all P<0.05]. NT thickness in monosomy X cases was greater than that of non-monosomy X cases [7.5 mm (1.0-17.4 mm) vs 1.7 mm (0.8-9.5 mm), Z=－5.25, P<0.001]. (4) Among the 72 pregnancies with indications other than ultrasound abnormalities, 68 underwent Down's syndrome screening and 61 underwent NIPT. The detection rates among the cases with positive results in Down's syndrome screening, NIPT for a sex chromosome abnormality, and other indications (advanced maternal age, adverse pregnancy history, and thalassemia genes carried by both parents) were 54.4% (37/68), 59.0% (36/61) and 22.2% (16/72), respectively ( χ 2=22.40, P<0.001). The detection rates of the cases with high-risk results from Down's syndrome screening and NIPT for sex chromosome abnormality were higher than that of the cases with other indications ( χ 2=18.77 and 15.40, both P<0.001). Of the 72 pregnancies, 19 (26.4%) were monosomy X and 53 (73.6%) were non-monosomy X, including 42 (58.3%) with chromosomal mosaicism. (5) Among the 205 cases of TS, 185 were successfully followed up (123 were monosomy X and 62 were non-monosomy X). There was one live birth in monosomy X cases (0.8%, 1/123) and 17 in non-monosomy X cases (27.4%, 17/62), and the difference was statistically significant ( χ2=33.22, P<0.001). Sixty-three TS cases with normal ultrasound findings were followed up (18 were monosomy X and 45 were non-monosomy X). In these cases, all 18 pregnancies with monosomy X and 32 (71.1%, 32/45) with non-monosomy X were terminated and the other 13 (28.9%, 13/45) cases of non-monosomy X were delivered. Of the 18 live births, one (non-monosomy X) was delivered at 36 weeks of gestation and the rest were born at term. Eleven cases of them were followed up. The height of one child with monosomy X was lower than the average height of children of the same age and sex by more than 2 standard deviations (－2 SD). The height of 10 children with non-monosomy X were between－1 SD and +3 SD among the children of the same age and gender. The mental and motor development were good in the 11 cases, and no other structural abnormalities were observed. The remaining seven cases refused to be followed up. Conclusions:Ultrasonographic abnormalities are the main indications of fetal TS with monosomy X, while positive Down's syndrome screening and positive NIPT for sex chromosome abnormality are indicators of non-monosomy X. The termination rate for pregnancies with monosomy X is higher than that for non-monosomy X.

Application value of modified magnetic bead screening for enrichment of cell-free fetal DNA from maternal peripheral blood in non-invasive prenatal testing / 中华围产医学杂志

Objective:To evaluate the value of modified magnetic bead screening for enrichment of cell-free fetal DNA (cffDNA) in non-invasive prenatal testing (NIPT).Methods:This study retrospectively recruited 31 cases with low concentration of cffDNA (<6.00%), Z value in the gray zone (3.00-4.00) at the first detection, or false-positive (confirmed by invasive prenatal diagnosis) or false-negative (confirmed by postnatal chromosome test) results among 11 000 pregnant women who underwent routine NIPT in Beijing Haidian District Maternal and Child Health Care Hospital from October 2017 to December 2019. Plasma samples collected for the first-time routine NIPT were used to enrich cffDNA using modified magnetic beads for NIPT (modified NIPT). Wilcoxon rank sum test was used to compare the modified NIPT with the routine NIPT in detecting the cffDNA concentrations of male fetuses.Results:Among the 31 pregnant women, there were 13 cases with low cffDNA concentration in routine NIPT, 11 having false-positive results in the routine NIPT (three for trisomy 13, four for trisomy 18 and four for trisomy 21, all were confirmed by invasive prenatal diagnosis), six with gray-zone Z values in the first-time NIPT (retesting indicating low risk) and one having false negative result for trisomy 21 (confirmed by postnatal chromosome test). Cell-free DNA (cfDNA) fragments less than 150 bp were effectively enriched using the modified magnetic bead screening and the concentration of cffDNA was increased from 4.43% (2.45%-17.61%) in routine NIPT to 13.46% (7.75%-36.64%) in the modified NIPT ( Z=-14.22, P<0.01). Results of the modified NIPT indicated that 13 cases with low cffDNA concentration of routine NIPT were successfully detected as low risk, as well as the risks in the six cases with gray-zone Z value and six of the 11 false-positive cases in the routine NIPT were low, which were consistent with the retest results of the routine NIPT, while high risk was found in one false-negative case. Conclusions:The modified NIPT could reduce the false positive rate by lowering the failure rate caused by low concentration of cffDNA and is able to identify false-negative cases. Compared with the routine NIPT, it shows a higher success rate and a lower false positive rate.

Clinical value of noninvasive prenatal testing in vanishing twin pregnancies / 中华围产医学杂志

Objective:To analyze the clinical value of noninvasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies.Methods:A total of 164 VT pregnancies that underwent NIPT in Peking University Third Hospital from January 2017 to December 2020 were enrolled. Gestational age at onset of vanishing, results of NIPT and invasive prenatal diagnosis, blood sampling time points, and pregnancy outcomes were retrospectively analyzed using two independent samples t test and Chi-square test. Results:(1) Of the 164 cases, six had positive results for NIPT, but negative results for karyotype analysis or single nucleotide polymorphism genotyping, with a false positive rate of 3.7% (6/164) for NIPT and all of them were delivered at term. Four pregnancies terminated in the second trimester, including two fetal malformation cases and one unexplained intrauterine death whose single nucleotide polymorphisms results are all normal and one inevitable abortion case due to premature rupture of membrane who refused amniocentesis. The other 154 women all gave birth to normal phenotype babies including 12 preterm ones. (2) The false-positive rate of NIPT was lower in VT pregnancies diagnosed at less than eight gestational weeks than those diagnosed after [1.5% (2/134) vs 13.3% (4/30), χ2=6.68, P=0.010]. The false-positive rate was 6.9% (4/58) in women diagnosed at or below eight weeks between the occurrence of VT and blood sampling and was 1.9% (2/106) in those with interval more than eight weeks, but without significant difference ( χ2=1.44, P=0.231). Conclusions:Although VT pregnancies exist false-positive results in NIPT, screening is still recommended based on fully informed consent to reduce unnecessary invasive prenatal diagnosis. The earlier the onset of VT, the lower the NIPT false positive rate, but whether extending the sampling interval would reduce the risk of false-positive needs further study.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Prenatal diagnosis indications and pregnancy outcomes and its impact factors in 1 372 pregnant women with fetal sex chromosome aneuploidy / 中华围产医学杂志

Objective:To analyze the indications for prenatal diagnosis and summarize the pregnancy outcomes and its influencing factors of pregnant women with fetal sex chromosome aneuploidy (SCA).Methods:This study retrospectively enrolled 1 372 fetuses prenatally diagnosed with SCA in Medical Genetics Center of Guangdong Women and Children Hospital from January 2013 to December 2021. The relationship between prenatal diagnosis indications and SCA as well as between ultrasound abnormalities, pregnancy outcomes and SCA types were analyzed by Chi-square test and trend Chi-square test. Results:The most common prenatal diagnosis indication was abnormal non-invasive prenatal testing (NIPT) (61.6%, 845/1 372). The most common SCA type was 47,XXY in cases with indications of abnormal NIPT and advanced maternal age, mosaic in cases with high or borderline risk of Down syndrome, and 45,X in cases with increased nuchal translucency or cystic hygroma. Of 1 372 pregnant women with fetal SCA, 17 were lost to follow-up, seven had intrauterine fetal death, and 1 348 (98.3%) were followed up for pregnancy outcomes including 36.3% (489/1 348) continued pregnancies and 63.7% (859/1 348) terminations. Pregnancy termination rates decreased sequentially in pregnant women carrying fetuses with 45,X, 47,XXY, mosaic, 47,XXX and 47,XYY [99.2% (247/249), 74.5% (307/412), 67.8% (156/230), 36.6% (86/235) and 28.4% (63/222), χ2trend=352.76, P<0.001]. There was no significant difference in pregnancy termination rates among the cases with different mosaic mutations (all P>0.05). The pregnancy termination rate was higher in fetuses with SCA complicated by ultrasound structural abnormalities than in those without ultrasound abnormalities and those with ultrasound soft markers [91.5% (182/199) vs 57.1% (535/937) and 67.0% (142/212), χ2 were 83.68 and 36.85, both P<0.001]. Moreover, the pregnancy termination rate in fetuses with SCA complicated by ultrasound soft markers was higher than those without ultrasound abnormalities ( χ2=7.13, P<0.05). Conclusions:NIPT abnormality is the most common indication for prenatal diagnosis of SCA. The types of SCA and ultrasound findings are important factors determining whether the pregnancy would be continued or not.

Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province / 中华妇产科杂志

Objective:To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects.Methods:Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed.Results:(1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively.Conclusions:NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Utilidad de la evaluación USG Doppler de las arterias uterinas entre las semanas 11 y 13+6 y su aplicación en las calculadoras de riesgo para predecir preeclampsia / Usefulness of the USG Doppler evaluation of the uterine arteries between weeks 11 and 13+6 and its application in risk calculators to predict preeclampsia / Utilidade da avaliação USG Doppler das artérias uterinas entre as semanas 11 e 13+6 e sua aplicação em calculadoras de risco para prever pré-eclâmpsia

Introducción. La preeclampsia es la primera causa de muerte materna directa en Colombia y la segunda a nivel mundial. El desarrollo de estrategias de predicción y prevención puede disminuir las complicaciones y secuelas ocasionadas por dicha enfermedad. El Doppler de arterias uterinas entre las semanas 11 y 13+6 como prueba independiente o en combinación con factores maternos o pruebas bioquímicas permite tasas de detección de preeclampsia temprana ≥ 90% a partir de la implementación de distintos cribados. La validez de dicha prueba diagnóstica presenta una sensibilidad del 47.8% y especificidad del 92.1% para la detección de preeclampsia temprana; con una sensibilidad del 26.4% y especificidad del 93.4% para predecir preeclampsia en cualquier etapa. División de los temas tratados. En esta revisión de tema se aborda la utilidad de esta medición, se habla de la realización de la técnica en cuestión y, por último, se revisan las herramientas estandarizadas que están disponibles en la actualidad junto con su accesibilidad y precisión. Conclusiones. La evidencia empírica que respalda la validez de las herramientas disponibles hoy en día para el tamizaje de preeclampsia a través de la evaluación por ultrasonografía Doppler de las arterias uterinas es significativa. Al ser Colombia un país que presenta una prevalencia alta de preeclampsia, conocer la utilidad de esta medición favorece una vigilancia temprana y oportuna, lo que disminuye los posibles desenlaces desfavorables para las maternas.

Introduction. Preeclampsia is the primary cause of direct maternal death in Colombia and the second globally. The development of prediction and prevention strategies can reduce complications and consequences caused by this disease. The uterine arteries Doppler between weeks 11 and 13+6 as an independent test or in combination with maternal factors or biochemical tests allows for early detection rates for preeclampsia of ≥90% from the implementation of different sieving. The validity of this diagnostic test has a sensitivity of 47.8% and specificity of 92.1% for the early detection of preeclampsia; with a sensitivity of 26.4% and specificity of 93.4% to predict preeclampsia at any stage. Division of Covered Topics. This topic review covers the usefulness of this measurement. It discusses the performance of the technique in question and, lastly, the standardized tools currently available are reviewed together with the accessibility and accuracy. Conclusions. The empirical evidence that supports the validity of the tools available today for the screening of preeclampsia via Doppler ultrasound evaluation of the uterine arteries is significant. As Colombia is a country with a high prevalence of preeclampsia, knowing the usefulness of this measurement favors early and timely surveillance, which reduces possible unfavorable outcomes for mothers.

Introdução. A pré-eclâmpsia é a principal causa de morte materna direta na Colômbia e a segunda no mundo. O desenvolvimento de estratégias de predição e prevenção pode reduzir as complicações e sequelas causadas pela doença. O Doppler da artéria uterina entre as semanas 11 e 13+6 como um teste independente ou em combinação com fatores maternos ou testes bioquímicos permite taxas de detecção de pré-eclâmpsia precoce≥90% a partir da implementação de diferentes exames. A validade desse teste diagnóstico tem sensibilidade de 47,8% e especificidade de 92,1% para a detecção de pré-eclâmpsia precoce; com uma sensibilidade de 26,4% e especificidade de 93,4% para prever pré-eclâmpsia em qualquer fase. Divisão dos tópicos abordados. Esta revisão de tópicos aborda a utilidade desta medição, discute a realização da técnica em questão e, por fim, são revisadas as ferramentas padronizadas que estão disponíveis atualmente, juntamente com sua acessibilidade e precisão. Conclusões. A evidência empírica que apoia a validade das ferramentas disponíveis atualmente para rastreamento de pré-eclâmpsia por meio da avaliação de ultrassom Doppler das artérias uterinas é significativa. Como a Colômbia é um país com alta prevalência de pré-eclâmpsia, conhecer a utilidade dessa medição favorece a vigilância precoce e oportuna, o que reduz possíveis resultados desfavoráveis para mulheres maternas.

Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing / 中华围产医学杂志

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

A case of maternal 45, X/46, XX mosaicism detected by non-invasive prenatal testing / 中华医学遗传学杂志

Objective@#To report on a case of maternally derived 45, X mosaicism detected by non-invasive prenatal testing (NIPT).@*Methods@#Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45, X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis.@*Results@#A maternal 45, X mosaicism was diagnosed. The fetus was confirmed to be normal.@*Conclusion@#Maternal 45, X masaicism can be diagnosed by NIPT.

Change in rates of prenatal tests for chromosomal abnormality over a 12-year period in women of advanced maternal age

OBJECTIVE: In 2007, the American College of Obstetricians and Gynecologists (ACOG) recommended that all pregnant women be offered screening or diagnostic tests for chromosomal abnormalities regardless of their age. Noninvasive prenatal testing (NIPT) for common chromosomal aneuploidies was introduced as a screening test in case of high-risk pregnancies. We assessed the rates of prenatal tests in women aged 35 years and older. METHODS: A retrospective study was conducted to compare the rates of amniocentesis, chorionic villus sampling (CVS), serum screening, and NIPT from January 2005 through March 2017 in women aged 35 years and older. We divided the initial 12 months after NIPT introduction into 4-month intervals, beginning in April 2016 through March 2017. RESULTS: The rates of amniocentesis were 56% before the ACOG statement, 38% between the ACOG statement and NIPT introduction, and 10% after NIPT introduction (P=0.001). The rates of CVS during the same periods were 0.5%, 2.1%, and 4.3% (P=0.016), respectively. The rates of serum screening were 44.2%, 61.3%, and 55.1% (P=0.049), respectively. During the 3 quarters after NIPT introduction, the rates of amniocentesis were 16.2%, 12.3%, and 7.3% (P=0.002), respectively; the rates of serum screening were 62%, 54%, and 46% (P=0.03), respectively; and the rates of NIPT were 19.9%, 30.3%, and 39.5% (P=0.007), respectively. The rates of CVS over the same periods were not significantly different. CONCLUSION: The ACOG statement and NIPT introduction significantly decreased the rate of amniocentesis in women of advanced maternal age. NIPT also reduced the rate of serum screening.

Amniotic fluid chromosome detection for 95 NIPT high-risk pregnant women / 国际检验医学杂志

Objective To analysis of the detection result of amniotic fluid chromosome which in NIPT high-risk pregnant women.Methods Amniotic fluid cells via amniotic cavity puncture were cultured and analyzed,the chromosome karyotypes were observed.Results The highest positive predictive value of NIPT was for trisomy 21(85.00%),then trisomy 18(75.00%),sex chromosome abnormalities(68.00%),other chromosome abnormalities(41.67%),trisomy 13 (25.00%).Conclusion The highest accuracy of NIPT was shown in detection of Down''s syndrome by NIPT.NIPT was screening test which is effective and noninvasive in prenatal diagnosis.Amniotic fluid Chromosomal karyotype analysis was the gold standard in the diagnosis of fetal chromosomal disease.

First trimester screening for trisomy 18 by a combination of nuchal translucency thickness and epigenetic marker level

PURPOSE: The aim of this study was to assess the diagnostic efficacy of noninvasive prenatal screening for trisomy 18 by assessing the levels of unmethylated-maspin (U-maspin) and fetal nuchal translucency (NT) thickness during the first trimester of pregnancy. MATERIALS AND METHODS: A nested case-control study was conducted using maternal plasma samples collected from 65 pregnant women carrying 11 fetuses with trisomy 18 and 54 normal fetuses. We compared the U-maspin levels, NT thicknesses, or a combination of both in the first trimester between the case and control groups. RESULTS: U-maspin levels and NT thickness were significantly elevated in the first trimester in pregnant women carrying fetuses with trisomy 18 when compared to those carrying normal fetuses (27.2 vs. 6.6 copies/mL, P<0.001 for U-maspin; 5.9 vs. 2.0mm, P<0.001 for NT). The sensitivities of the U-maspin levels and NT thickness in prenatal screening for fetal trisomy 18 were 90.9% and 90.9%, respectively, with a specificity of 98.1%. The combined U-maspin levels and NT thickness had a sensitivity of 100% in prenatal screening for fetal trisomy 18, with a specificity of 98.1%. CONCLUSION: A combination of U-maspin levels and NT thickness is highly efficacious for noninvasive prenatal screening of fetal trisomy 18 in the first trimester of pregnancy.

The application of chromosome specific site selection method in noninvasive prenatal testing / 临床检验杂志

Objective To establish a noninvasive prenatal testing(NIPT) method based on the chromosome specific site sequencing instead of the conventional whole genome sequencing.Methods Blood plasma samples from 200 pregnant women with known fetus karyotypes were collected.First,the specific loci on chromosome 13,18 and 21 were selected by the database filter.Then,these specific loci were captured by probes,and were performed sequencing.Finally,chromosome aneuploidy was identified by the Z-score.ResultsSeven fetuses with 21-trisomy syndrome,3 with 18-trisomy syndrome and 1 with 13-trisomy syndrome were detected by the chromosome specific site sequencing,and the results were accordant with those of the whole genome sequencing method.Conclusion The NIPT method based on the chromosome specific site sequencing has the advantages of low cost and high throughput,which may replace the NIPT method based on the whole genome sequencing.