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Objective: To expand the limited knowledge on cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy by updating the data from The Fetal Medicine Foundation (FMF) on prospective first-trimester screening and those identified in a systematic review of the literature., Methods: The FMF data were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation using the Harmony® prenatal test. A search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the International Clinical Trials Registry Platform (World Health Organization) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancy, irrespective of gestational age at testing, in which data on pregnancy outcome were provided for at least 85% of the study population. Meta-analysis was performed using the FMF data and data from the studies identified by the literature search. This review was registered in the PROSPERO international database for systematic reviews RESULTS: In the FMF study, cfDNA testing was carried out in 1442 twin pregnancies and a result was obtained, after first or second sampling, in 1367 (94.8%) cases. In 93.1% (1272/1367) of cases, there was prenatal or postnatal karyotyping or birth of phenotypically normal babies; 95 cases were excluded from further analysis either because the pregnancy ended in termination, miscarriage or stillbirth with no known karyotype (n = 56) or there was loss to follow-up (n = 39). In the 1272 pregnancies included in the study, there were 20 cases with trisomy 21, 10 with trisomy 18, two with trisomy 13 and 1240 without trisomy 21, 18 or 13. The cfDNA test classified correctly 19 (95.0%) of the 20 cases of trisomy 21, nine (90.0%) of the 10 cases of trisomy 18, one (50.0%) of the two cases of trisomy 13 and 1235 (99.6%) of the 1240 cases without any of the three trisomies. The literature search identified 12 relevant studies, excluding our papers because their data are included in the current study. In the combined populations of our study and the 12 studies identified by the literature search, there were 137 trisomy-21 and 7507 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 99.0% (95% CI, 92.0-99.9%) and 0.02% (95% CI, 0.001-0.43%), respectively. In the combined total of 50 cases of trisomy 18 and 6840 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 92.8% (95% CI, 77.6-98.0%) and 0.01% (95% CI, 0.00-0.44%), respectively. In the combined total of 11 cases of trisomy 13 and 6290 non-trisomy-13 pregnancies, the pooled weighted DR and FPR were 94.7% (95% CI, 9.14-99.97%) and 0.10% (95% CI, 0.03-0.39%), respectively., Conclusions: In twin pregnancy, the reported DR of trisomy 21 by cfDNA testing is high, but lower than that in singleton pregnancy, whereas the FPR appears to be equally low. The number of cases of trisomy 18 and more so trisomy 13 was too small for accurate assessment of the predictive performance of the cfDNA test. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To identify the most common ultrasound patterns of markers and anomalies associated with Patau syndrome (PS), to explore the efficacy of multiparameter sonographic protocols in detecting trisomy 13 (T13) and to analyze the influence of maternal age (MA) on screening performance., Methods: The project was a prospective study based on singleton pregnancies referred for a first-trimester screening examination. The scan protocol included nuchal translucency (NT), fetal heart rate (FHR), secondary ultrasound markers [nasal bone (NB), tricuspid regurgitation (TR), ductus venosus reversed a-wave (revDV)] and major anomaly findings., Results: The study population comprised 6133 pregnancies: 6077 cases of euploidy and 56 cases of T13. Statistically significant differences were found in MA, FHR, NT, absence of NB, presence of revDV, TR and single umbilical artery. Fourteen cases of T13 (25%) demonstrated no markers of aneuploidy. The best general detection rate (DR) (DR of 78.6% with an false positive rate (FPR) of 1.2%) was obtained for a cutoff of 1/300 utilizing the "NT+T13" algorithm. The logistic regression model revealed that the central nervous system (CNS) anomalies had the greatest odds ratio (of 205.4) for T13., Conclusions: The effectiveness of the multiparameter sonographic protocol used for T13 screening showed promising results in patients older than 36 years and suboptimal results in patients between 26 and 36 years old. When screening for T13 left heart defects, CNS anomalies, abdominal anomalies, FHR above the 95th percentile, increased NT, revDV and lack of NB should receive specific attention., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11-13 weeks' gestation are reduced in pregnancies with fetal trisomy and in those that subsequently develop pre-eclampsia (PE). In screening for trisomy, the established biochemical marker is PAPP-A, whereas in screening for PE, the preferred marker is PlGF. The objective of this study was to examine the impact of replacing PAPP-A by PlGF in first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency thickness (NT) and free β-human chorionic gonadotropin (β-hCG)., Methods: This was a prospective screening study in singleton pregnancies for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and serum PAPP-A and free β-hCG at 11-13 weeks' gestation in which we also measured PlGF. Multiples of the median (MoM) values were calculated for PAPP-A, free β-hCG and PlGF. The dataset was split randomly into training and test datasets of roughly equal size, and the parameters for PlGF obtained from the training dataset were used in risk calculation for the test dataset. Standardized detection rates were computed by obtaining the likelihood ratios for biochemistry and fetal NT for trisomy-21, -18 and -13 pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific detection rates. These were then weighted according to the maternal age distributions of trisomy-21, -18 and -13 pregnancies in England and Wales in 2018. Similarly, standardized false-positive rates (FPR) were computed by obtaining the likelihood ratios for biochemistry and NT, as appropriate, in normal pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific FPRs. A modeling approach was used to assess the performance of screening according to gestational age at biochemical testing., Results: The study population of 71 266 pregnancies included 70 858 (99.4%) with normal fetal karyotype or birth of a phenotypically normal neonate and 263 with trisomy 21, 109 with trisomy 18 and 36 with trisomy 13. There are five main findings of this study. First, the performance of screening for trisomy by the first-trimester combined test or the combined test in which PAPP-A is replaced by PlGF is substantially better at 11 than at 13 weeks' gestation; for example, the detection rates of trisomy 21 by the combined test were 94%, 90% and 84%, at 5% FPR, when testing was carried out at 11, 12 and 13 weeks, respectively, and the corresponding values in screening by a test in which PAPP-A is replaced by PlGF were 90%, 87% and 86%, respectively. Second, in trisomy-21 pregnancies, the deviation of median PAPP-A MoM from normal decreases with increasing gestational age, whereas the deviation in PlGF does not change with gestational age. Third, the performance of screening for trisomy 21 during the 11 th and 12 th gestational weeks is superior if screening includes PAPP-A rather than PlGF, whereas during the 13 th week the performance is slightly higher with the use of PlGF rather than PAPP-A. Fourth, in our population with mean gestational age at testing of 12.7 weeks, screening by maternal age, fetal NT, serum free β-hCG and serum PAPP-A predicted 88%, 96% and 97% of cases of fetal trisomies 21, 18 and 13, respectively, at a FPR of 5%; the respective values in screening by a test in which PAPP-A is replaced by PlGF were 85%, 96% and 96%. Fifth, addition of serum PlGF does not improve the prediction of trisomy provided by maternal age, fetal NT and serum free β-hCG and PAPP-A., Conclusion: In first-trimester screening for trisomy, the preferred biochemical marker is PAPP-A rather than PlGF, especially when biochemical testing is carried out during the 11 th week of gestation or earlier. However, if PlGF was to be used rather than PAPP-A, the same detection rate can be achieved but at a higher FPR. This may be an acceptable compromise to minimize cost and achieve effective screening for both trisomy and PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy and to define the performance of the test by combining our results with those identified in a systematic review of the literature., Methods: The data for the prospective study were derived from screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation. Two populations were included; first, self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and, second, women selected for the cfDNA test after routine first-trimester combined testing at one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) was carried out to identify all peer-reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancy. A meta-analysis was then performed using our data and those in the studies identified by the literature search., Results: In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 cases of trisomy 21, nine (90.0%) of the 10 cases of trisomy 18, one (50.0%) of the two cases of trisomy 13 and 962 (99.4%) of the 968 cases without any of the three trisomies. The literature search identified seven relevant studies, excluding our previous papers because their data are included in the current study. In the combined populations of our study and the seven studies identified by the literature search, there were 56 trisomy-21 and 3718 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 98.2% (95% CI, 83.2-99.8%) and 0.05% (95% CI, 0.01-0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3143 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 88.9% (95% CI, 64.8-97.2%) and 0.03% (95% CI, 0.00-0.33%), respectively. For trisomy 13, there were only three affected cases and two (66.7%) of these were detected by the cfDNA test at a FPR of 0.19% (5/2569)., Conclusions: The performance of cfDNA testing for trisomy 21 in twin pregnancy is similar to that reported in singleton pregnancy and is superior to that of the first-trimester combined test or second-trimester biochemical testing. The number of cases of trisomies 18 and 13 is too small for accurate assessment of the predictive performance of the cfDNA test. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background: We evaluated the performance of a cell-free DNA (cfDNA) prenatal screening assay for trisomies 21, 18, and 13, and sex chromosome aneuploidies (SCAs) among a population of pregnant women that included both those at average and high risk., Methods: Specimen collection, cfDNA extraction, massively parallel sequencing, and bioinformatics analysis were conducted per laboratory protocol. Assay results, concordance with pregnancy outcomes, and performance characteristics were evaluated., Results: A total 75,658 specimens from 72,176 individual pregnant women were received. Technical reasons accounted for 288 (0.4% of all received samples) tests not performed. In the final analysis cohort (N = 69,794), 13% of pregnancies were considered at average risk and 87% at high risk. Mean gestational age at specimen collection was 15.1 weeks. Of the 69,794 unique pregnancies, 1,359 (1.9%) had positive test results. Among the results with confirmed outcomes, PPV for trisomies 21, 18, and 13 was 98.1%, 88.2%, and 59.3%, respectively; the PPV was 69.0% for SCAs and 75.0% for microdeletions. Overall, PPV was 87.2%, sensitivity was 97.9%, and specificity was 99.9%., Conclusion: This cfDNA prenatal screening assay provides highly accurate discrimination between affected and unaffected pregnancies among a population of pregnant women at average and high risk for fetal genetic abnormalities., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objectives: To assess the performance of first trimester combined screening (FTS) when enhanced with placental growth factor and alpha feto-protein in the detection of trisomies 18 and 13., Methods: A retrospective case-control study. Marker parameters were derived using frozen serum samples. Multivariate Gaussian modelling predicted the detection rate (DR) and false-positive rate (FPR) for trisomies 18 and 13 with FTS and enhanced first trimester screening (eFTS) using the risk of trisomy 21 alone and an additional risk cut-off for trisomy 18, or trisomies 18 or 13., Results: There were 83 trisomy 18, 22 trisomy 13, and 588 controls. The median placental growth factor levels in trisomies 18 and 13 were 0.75 and 0.65 multiple of the median of controls, respectively (both P < 0.0001). There were no statistically significant differences in alpha feto-protein levels. Modelling predicts that using a trisomy 21 risk cut-off alone, at FPR of 3%, eFTS increases the DR for trisomies 18 and 13 by 0.6-0.8% compared with FTS. Additionally using a trisomy 18 risk cut-off, at an extra FPR of 0.2%, eFTS increased the DR by 0.6-0.9% over FTS; using a trisomy 18 or 13 risk cut-off did not further increase detection for FTS or eFTS. The increase in DR was greater at higher FPR., Conclusion: eFTS increases the detection of trisomies 18 and 13 to a small extent., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Perinatal palliative care allows for an active partnership among a pregnant woman, her family, and her multidisciplinary treatment team and addresses her specialized medical care, emotional, social, and familial needs when a life-limiting fetal diagnosis is confirmed. The purpose of this article is to highlight the multidisciplinary care model used within a perinatal palliative care program. A case study provides a unique perspective on support needed for parents who anticipate that their newborn may die before or shortly after birth., (Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the impact of the introduction of prenatal screening on time of detection and pregnancy outcome for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13)., Methods: We performed a retrospective, population-based cohort study in the Northern Netherlands including 503 trisomy cases born between 2005 and 2012. Screening tests and invasive procedures, timing of diagnosis and pregnancy outcome were compared between the period before (2005-2006) and after introduction (2007-2012) using X 2 tests., Results: There was an increase in proportion of women who had a prenatal screening and/or invasive test, from 62% in 2005-2006 to 84% in 2010-2012 (p < 0.01), while the proportion of prenatally diagnosed cases did not change (60% overall). In women < =35 years 47% of the cases were diagnosed prenatally vs 73% in women >35 years (p < 0.01). More T13/T18 cases were diagnosed <24 weeks after introduction (62% vs 84%; p < 0.01). In T13/T18 intra-uterine death decreased (26% vs 15%), while terminations increased: 55% vs 72%., Conclusion: The introduction of prenatal screening had limited impact on the time of detection and outcome of the most common trisomies. The introduction of the 20-week anomaly scan has resulted in more trisomy cases diagnosed <24 weeks and a shift from fetal death to terminations.

Objective: Antenatal reflex DNA screening for Down's syndrome has a high screening performance. We aimed to determine the performance of trisomy 18 and trisomy 13 reflex DNA screening when added to Down's syndrome screening., Methods: In our modelled screening protocol, women provide two samples: a serum sample for a Combined test and a plasma sample for a possible DNA test. Women with Down's syndrome, trisomy 18, or trisomy 13 Combined test risks above a single cut-off have a reflex DNA test using the plasma sample, without the need to recall them to collect another sample and provide counselling. Women with a failed DNA test (after a second attempt using a fresh plasma sample) have an Integrated test, and are classified as positive if any of the Down's syndrome, trisomy 18, or trisomy 13 Integrated test risks are greater than 1 in 25., Results: At 1 in 800 term risk cut-offs for Down's syndrome, trisomy 18, and trisomy 13, an estimated 10% of women are reflexed to DNA screening, yielding a 91% Down's syndrome detection rate, an 89% trisomy 18 detection rate, and a 79% trisomy 13 detection rate for a 0.05% false-positive rate. At a 1 in 1900 term risk cut-off for Down's syndrome, trisomy 18, or trisomy 13, an estimated 20% of women are reflexed to DNA screening, and this yields a 94% Down's syndrome detection rate, a 92% trisomy 18 detection rate, and an 84% trisomy 13 detection rate for a 0.10% false-positive rate., Conclusion: Reflex DNA screening for trisomies 18 and 13 can be usefully added to reflex DNA screening for Down's syndrome., (© The Author(s) 2016.)

Objective: To estimate the performance of antenatal sequential Integrated screening for Down's syndrome (DS), trisomy 18 (T18) and trisomy 13 (T13), in which women have first trimester testing for each disorder; those above specified risk cut-offs are screen-positive, and the remainder continue to Integrated testing, using first and second trimester screening markers together., Methods: Published screening marker parameters and Monte Carlo simulation were used to calculate detection rates (DR's) and risk cut-off levels for specified false-positive rates (FPR's), and DR's and FPR's for specified risk cut-offs. We compared this screening performance with that based on all women having Integrated tests., Results: Sequential Integrated DS screening detects 71% of DS pregnancies at the first trimester stage at a 0.5% FPR. For an overall 2% FPR, the DS DR is 92%, the same screening performance as the Integrated test performed on all women. Sequential Integrated T18 and T13 screening detects 70% of T18 and 53% of T13 pregnancies at the first trimester stage at a 0.05% FPR for each. The overall T18 and T13 DR's are 96% and 72% respectively at 0.2% FPR, the same screening performance as with Integrated tests performed on all women. Increasing the overall FPR's does not materially increase the DR's for any of the three disorders., Conclusion: The performance of sequential Integrated screening is similar to the performance if all women have an Integrated test, but has the advantage of identifying most DS, T18, and T13 pregnancies a few weeks earlier., (© The Author(s) 2015.)

Objective: To compare the performance of antenatal screening for Down's syndrome (DS), trisomy 18 (T18), and trisomy 13 (T13) using a single risk of being affected by one of the three disorders, with the performance using separate risks for each disorder., Methods: Screening performance was estimated using Monte Carlo simulation based on published parameters for the Integrated, Combined, and Quadruple tests. Detection rates (DRs) were calculated using a single risk and separate risks for each disorder at given false-positive rates (FPRs)., Results: With separate risks, using a 3% DS test FPR and 0.2% FPRs for the T18 and T13 tests, the overall FPRs for the Integrated and Combined tests are both 3.3%. For the same overall FPR (3.3%), the use of a single risk with the Integrated test increases the T13 DR from 76% to 82%, with unchanged DS and T18 DRs (94% and 92% respectively). With the Combined test, it increases the T13 and T18 DRs (from 89% to 91% and 77% to 81% respectively), with unchanged DS DR (85%). With separate risks, using a 5% DS test FPR and 0.2% FPRs for the T18 and T13 tests, the overall FPR for the Quadruple test is 5.4%. For the same overall FPR (5.4%), the use of a single risk increases the T18 DR from 61% to 67% with unchanged DS and T13 DRs (87% and 33% respectively)., Conclusions: Reporting a single risk estimate for the three disorders is less confusing than reporting separate risks and can yield the same or better screening performance., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objective: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies., Methods: Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 4 January 2015., Results: In total, 37 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.2% (95% CI, 98.5-99.6%) and 0.09% (95% CI, 0.05-0.14%), respectively, for trisomy 21, 96.3% (95% CI, 94.3-97.9%) and 0.13% (95% CI, 0.07-0.20) for trisomy 18, 91.0% (95% CI, 85.0-95.6%) and 0.13% (95% CI, 0.05-0.26%) for trisomy 13, 90.3% (95% CI, 85.7-94.2%) and 0.23% (95% CI, 0.14-0.34%) for monosomy X and 93.0% (95% CI, 85.8-97.8%) and 0.14% (95% CI, 0.06-0.24%) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR for trisomy 21 was 93.7% (95% CI, 83.6-99.2%) and the FPR was 0.23% (95% CI, 0.00-0.92%)., Conclusion: Screening for trisomy 21 by analysis of cfDNA in maternal blood is superior to that of all other traditional methods of screening, with higher DR and lower FPR. The performance of screening for trisomies 18 and 13 and sex chromosome aneuploidies is considerably worse than that for trisomy 21., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To examine the potential impact of combining measures from cell-free DNA (cfDNA) testing with maternal age and first-trimester biomarkers in screening for fetal trisomies., Methods: This was a theoretical study using Bayes' theorem to combine the a priori risk for fetal trisomy 21 derived from maternal age with likelihoods from nuchal translucency thickness, serum pregnancy-associated plasma protein-A, serum free β-human chorionic gonadotropin and plasma cfDNA. We adopted a binomial counting model for the cfDNA likelihoods and developed a model to account for errors in estimating fetal fraction., Results: When Bayes' theorem was used to combine the a priori risk for trisomy 21 derived from the first-trimester combined test with likelihoods from the cfDNA test, and when the true fetal fraction was known, the detection rate increased from 62% at a fetal fraction of 4% to 100% at a fetal fraction of ≥ 9%; the positive likelihood ratio (trisomic/euploid) increased from 620 to 1000 and the negative likelihood ratio (euploid/trisomic) increased from 3 to > 10 000. When the fetal fraction is < 4%, the cfDNA test has traditionally been considered to be a failure, but the cfDNA results can be used to improve the performance of screening by the combined test., Conclusions: In contingent policies that use the first-trimester combined test for first-line screening to select the subgroup for cfDNA testing, the data from the latter should be used to update the risk from the former. Individual patient results from cfDNA testing depend crucially on the fetal fraction and the precision of its measurement., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

A 31‐year‐old primiparous woman underwent non‐invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t‐statistics (Z‐score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development. [ABSTRACT FROM AUTHOR]

Objective: We present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues. Case Report: A 38-year-old, gravida 3, para 0, woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 47,XX,+13[2]/ 46,XX[20] in co-twin A and a karyotype of 46,XY in co-twin B. In co-twin A, among 22 colonies of cultured amniocytes, two colonies had a karyotype of 47,XX,+13, whereas the rest 20 colonies had the karyotype of 46,XX. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr (1-22,X) × 2, Y × 0 and detected no genomic imbalance. Prenatal ultrasound and parental karyotypes were normal. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from the parental bloods and cultured amniocytes excluded uniparental disomy (UPD) 13. The woman was encouraged to continue the pregnancy. At 37 weeks of gestation, a normal 2410-g female co-twin A and a normal 2360-g male co-twin B were delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta of co-twin A were 46,XX (40/40 cells), 47,XX,+13 [1]/46,XX[39] and 47,XX,+13[36]/46,XX [4], respectively. QF-PCR analysis on cord blood of co-twin A excluded UPD 13. When follow-up at age 1½ years, the neonate of co-twin A was normal in physical and psychomotor development. Conclusion: Low-level true mosaic trisomy 13 at amniocentesis can be associated with a favorable fetal outcome and cytogenetic discrepancy in various tissues.

Background: Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy.Materials and Methods: In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown–rump length (CRL) and pregnancy-associated plasma protein-A (PAPP-A), and free beta of human chorionic gonadotropin (fβhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated.Results: The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high-risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P0.05).Conclusion: Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities.

Background: Trisomy 13 (T13) and sex chromosome aneuploidies (SCA) are the vital causes of congenital malformations. This study was performed to identify the T13 and SCA with screening tests in the first trimester of pregnancy. Materials and Methods: In this cross-sectional study, first-trimester combined screening was conducted on 2100 pregnant women referred to Narges Genetics Laboratory, Ahvaz, Iran. Evaluating the first trimester screening tests, including nuchal translucency (NT), crown--rump length (CRL) and pregnancy-associated plasma protein-A (PAPP- A), and free beta of human chorionic gonadotropin (fβhCG) was performed. For a definitive diagnosis of T13 and SCA syndrome, fetal karyotype was evaluated. Results: The average NT and CRL in high-risk group for T13 were 5.96 mm and 61.7 mm respectively and in high- risk groups for SCA were 3.7 mm and 75.9 mm, respectively. Significant correlation was observed among NT, CRL and T13, SCA (P<0.05). The average serum fβhCG and PAAP-A levels in high-risk group for T13 were 0.42 and 0.31, respectively. Significant correlation was observed between decrease fβhCG, PAPP-A and T13 levels and increase fβhCG levels and SCA levels (P<0.05). No Significant correlation was observed between PAPP-A levels and SCA levels (P>0.05). Conclusion: Using special software and karyotype testing, the prenatal screening tests based on the maternal age and gestational age in the first trimester of pregnancy may determine the major risk of fetal chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Background: A fast adoption of a non-invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. The aim of the study-to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow.Methods: Based on the first trimester combined prenatal screening results 12,700 pregnant women were classified as a high-risk (cut-off ≥ 1:100) and an intermediate-risk (cut-off 1:101 - 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results from intermediate-risk group were considered for invasive prenatal diagnostic.Results: 258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p < 0.05) were revealed for fetal fraction (FF) and both for some patient's (body mass index and weight) and fetus's (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as specificity for common trisomies and SCAs with an overall false positive rate 0.3%.Conclusions: NIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women. [ABSTRACT FROM AUTHOR]

Fetal congenital heart disease (CHD) is often associated with chromosomal abnormalities. Our primary aim was to assess stillbirth and neonatal mortality rates for pregnancies complicated by trisomies 13, 18, and 21 in the presence of CHD, from a single tertiary referral center during 2000–2020 in a retrospective cohort study. The secondary aims were to investigate maternal morbidity in these pregnancies, and to study the gestational or neonatal age when mortality occurred. Inclusion criteria were the prenatal diagnosis of at least one structural CHD, together with prenatally diagnosed fetal trisomy 13, 18, or 21. One-hundred and sixty patients with fetal trisomy 13 (14.4%), fetal trisomy 18 (28.8%), and fetal trisomy 21 (56.9%) were evaluated. In total, 98 (61.3%) families opted for the termination of pregnancy (TOP). Of the remaining 62 (38.8%) pregnancies, 16 (25.8%) resulted in intrauterine fetal death/death during delivery. Ten out of twenty-one (47.6%) infants with trisomy 13 or 18 were born alive. The livebirth rate was 87.8% (36/41) for infants with trisomy 21. Early neonatal death was observed in nine (19.6%) infants. Thirty-one (86.1%) infants with trisomy 21 survived the first year of life. These data may be helpful for counseling affected parents when the decision to terminate or continue the pregnancy should be considered. [ABSTRACT FROM AUTHOR]

BackgroundSince its commercial release in 2011 cell-free DNA screening has been rapidly adopted as a routine prenatal genetic test. However, little is known about its performance in actual clinical practice.ObjectiveWe sought to investigate factors associated with the accuracy of abnormal autosomal cell-free DNA results.Study designWe conducted a retrospective cohort study of 121 patients with abnormal cell-free DNA results from a referral maternal-fetal medicine practice from March 2013 through July 2015. Patients were included if cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, or microdeletions (if reported by the laboratory) were positive or nonreportable. The primary outcome was confirmed aneuploidy or microarray abnormality on either prenatal or postnatal karyotype or microarray. Secondary outcomes were identifiable associations with in vitro fertilization, twins, ultrasound findings, testing platform, and testing laboratory. Kruskal-Wallis or Fisher exact tests were used as appropriate.ResultsA total of 121 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, and/or microdeletions. In all, 105 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, and trisomy 13. Of these, 92 (87.6%) were positive and 13 (12.4%) were nonreportable. The results of the 92 positive cell-free DNA were for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%), and positive for >1 parameter (3, 3.3%). Overall, the positive predictive value of cell-free DNA was 73.5% (61/83; 95% confidence interval, 63-82%) for all trisomies (by chromosome: trisomy 21, 83.0% [39/47; 95% confidence interval, 69-92%], trisomy 18, 65.0% [13/20; 95% confidence interval, 41-84%], and trisomy 13, 43.8% [7/16; 95% confidence interval, 21-70%]). Abnormal cell-free DNA results were associated with positive serum screening (by group: trisomy 21 [17/48, 70.8%]; trisomy 18 [7/22, 77.8%]; trisomy 13 [3/17, 37.5%]; nonreportable [2/13, 16.7%]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45, 55.6%]; trisomy 18 [13/20, 65%]; trisomy 13 [6/14, 42.9%]; nonreportable [1/13, 7.7%]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories (P = .018). In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives.ConclusionThe positive predictive value of 73.5% for cell-free DNA screening for autosomal aneuploidy is lower than reported. The positive predictive value for microdeletion testing was 0%. Diagnostic testing is needed to confirm abnormal cell-free DNA results for aneuploidy and microdeletions.

Aims: To compare the screening capability of ultrasonography in detecting trisomy 13 (T13) using a multiparameter sonographic protocol (NT+) with a classical combined screening test (CST) protocol.Methods: The project was a prospective, multicenter study based on a nonselected mixed-risk population of women referred for a first-trimester screening examination. Each subject was offered a choice between either the gold standard, traditional combined screening test (CSG arm) or the ultrasound-based screening protocol (USG arm). General and MA-based screening performances were checked.Results: The study population comprised 20,887 pregnancies: 12,933 in the CSG arm, including 27 cases of T13, and 7954 in the USG arm, including 30 cases of T13. The DR for T13 was higher in the CSG arm than in the USG arm for all tested cutoff points: 1/50 (88.5 versus 63.3%, respectively), 1/100 (88.5 versus 70%, respectively) and 1/300 (92.3 versus 83.3%, respectively). Using the ROC curves for fixed FPRs of 3 and 5%, the T13 detection rate in our study reached 90 and 93%, respectively, in the USG arm and 92 and 96%, respectively, in the CSG arm. MA influenced the T13 screening performance in the USG arm and reduced the DR in patients <31 years. Such influence was not detected in the CSG arm.Conclusions: Classic CST was more effective in detecting T13 than the ultrasound-only approach. However, the recommended cutoff of 1/50 showed unsatisfactory results for both traditional CST and the multiparameter sonographic test we proposed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of secondary screening using non‐invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn‐around times (TATs) and no‐call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. Design: Retrospective cohort. Setting: London teaching hospital. Sample: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell‐free DNA screening laboratory – the SAFE laboratory. Methods: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no‐call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure. Main outcome measures: Test performance, TATs and no‐call rates, factors affecting no‐call results. Results: Average TAT was 4.0 days (95% CI 4.0–4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9–99.9%) and 90.4% (95% CI 80.0–96.8%), respectively. The overall no‐call rate was 32/8651 (0.37%, 95% CI 0.26–0.52%). The overall risk of a no‐call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low‐molecular‐weight heparin. Conclusions: High‐throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no‐calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low‐molecular‐weight heparin and past history of malignancy did not have major impacts on test no‐call rates and should not constitute reasons for withholding the option of NIPT from women. Turn‐around times of 4 days, no‐call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS. Turn‐around times of 4 days, no‐call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of NIPT by combining our cohort study results with published studies in a systematic meta-analysis.Material and Methods: A cohort study was carried out in the First Affiliated Hospital of Sun Yat-sen University and Kanghua Hospital. Meanwhile, searches of PubMed, EMBASE, The Cochrane Library and Web of Science for all relevant peer-reviewed articles were performed with a restriction to English language publication before 15 June 2019. Quality assessments were conducted with the Quality Assessment Tool for Diagnostic Accuracy Studies-2 checklist. Data analysis, heterogeneity, subgroup analysis and publication bias were carried out using META-DISC 1.4 and STATA 12.0.Results: In all, 141 twin pregnancies included in our cohort study; confirmation revealed one true-positive case for trisomy 21 and 140 true-negative cases. The sensitivity and specificity for trisomy 21 by NIPT were both 100%. Twenty-two eligible studies were enrolled in this meta-analysis together with our study. There were 199 cases of trisomy 21, 58 cases of trisomy 18, 14 cases of trisomy 13 and 6347 cases of euploids in total. For trisomy 21, NIPT showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.99, 1.00, 145.81, 0.06 and 1714.09, respectively. For trisomy 18, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.88, 1.00, 200.98, 0.19 and 483.68, respectively.Conclusions: The performance of NIPT for trisomy 21 in twin pregnancy was excellent and it was similar to that reported in singleton pregnancy. However, due to publication bias (trisomy 18) and small number of cases (trisomy 13), accurate assessment of the predictive performance of NIPT for trisomies 18 and 13 could not be achieved. [ABSTRACT FROM AUTHOR]

Objectives: Recent years have witnessed a shift from invasive methods of prenatal screening to non-invasive strategies. Accordingly, non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has gained a considerable deal of interest from both geneticists and obstetricians. Efficacy of this method in identification of common aneuploidies has been extensively assessed in singleton pregnancies. However, a limited number of studies have addressed the twin pregnancies. In this context, the present study is aimed at identification of the efficacy of NIPT in twin pregnancies. Methods: NIPT was performed on twin pregnancies to screen trisomies 13, 18 and 21. Pregnant women referring to Nilou Clinical Laboratory between March 2016 and December 2018 were included in this research. Results: In the current study, a total 356 twin pregnancies were screened in search for trisomies 13, 18 and 21. 6 cases exhibited positive NIPT results in which the presence of trisomies 13, 18 and 21 was confirmed by fetal karyotype in 1, 2 and 2 cases, respectively. One twin pregnancy showed normal karyotype. The combined false-positive rate for these trisomies was 0.28%. No false negative case was observed. The combined sensitivity and specificity of NIPT in twin pregnancies were 100 and 99.7%, respectively. Conclusion: The results of the current study verify the feasibility, sensitivity and specificity of NIPT in twin pregnancies. [ABSTRACT FROM AUTHOR]

Introduction: Trisomy 13 is the third most common of the autosomal trisomies compatible with viability. We hereby report a case of a fetus with trisomy 13 during a second trimester sonographic examination. Case presentation: A 37-year-old woman attended to our department with a positive pregnancy test and a period of amenorrhea of 15 weeks. Ultrasound examination showed an intrauterine pregnancy with viable fetus, reduced levels of amniotic fluid. Holoprosencephaly was identified by ultrasonography, nasal bone and stomach were not visible, and fetal growth retardation occurred. The woman along with her husband were referred for genetic counseling and decided pregnancy termination. A medical induced miscarriage occurred, followed by curettage. Histopathology of the specimen revealed holoprosencephaly, bilateral absence of the optic nerves, hypoplastic nasal bones, absence of nasal septum, cleft lip and cleft palate. Abnormal heart shape with hypoplastic left ventricle and wall thickness of the right ventricle were noticed. Syndactyly occured between middle and ring fingers and between second and third toes. Extensive calcium deposits in the placenta and a two-vessel umbilical cord were also reported. All the above congenital anomalies are compatible with Trisomy 13. Discussion: Trisomy 13 can be sonographically detected when a complete morphology scan of the fetus, including the heart, is performed. Because the prognosis of the syndrome is very poor, early prenatal diagnosis is important. [ABSTRACT FROM AUTHOR]

Objective: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy.Methods: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.Results: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18.Conclusion: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

We report the case of a 24-year-old Japanese woman, gravida 2, para 1, who became pregnant spontaneously. At 24 weeks of gestation, her fetus was found to have various abnormalities, including holoprosencephaly, congenital heart disease and severe fetal growth restriction, and she was referred to our hospital. From these findings, the fetus was suspected of having a chromosomal aberration, in particular, trisomy 13, and after genetic counseling, amniocentesis for chromosomal analysis was performed. Although the results of fluorescent in situ hybridization (FISH) analysis showed no numeric abnormalities, G-banding analysis revealed a ring chromosome 13; 46, XX, r (13) (p13q32). At 41 weeks of gestation, she delivered a female baby weighing 2240 g with good condition. The respiratory status of the neonate was stable, and she was discharged 30 days after birth. Ring chromosomes are rare chromosomal aberrations, and obstetricians should recognize that ring chromosomes cannot be detected solely by FISH analysis and require G-banding analysis and that information on the ring breakpoint is needed to counsel the parents regarding the fetal and neonatal prognosis. [ABSTRACT FROM AUTHOR]

Families that choose to continue a pregnancy with a prenatal diagnosis of Trisomy 13/18 are a minority that present unique challenges for those in charge of their care. This study investigated the extent to which these patients felt supported by their healthcare providers, and any differences in the perceived level of support experienced by those working with a physician versus those working with a genetic counselor. Two online support groups, SOFT and Hope for Trisomy, distributed an online survey to their members. Means, standard deviations and chi-square analysis were calculated to describe their responses. One-hundred fourteen surveys were included in the final analysis. Respondents were more likely to agree that genetic counselors provided unbiased information in a way that they understood, compared to physicians. Review of qualitative responses found that portrayal of Trisomy 13/18 by healthcare providers used directive language when describing the lethality, morbidity and burden of the condition. Language included terms such as “incompatible with life” and comments on burden to other family members. Healthcare providers can assist families that receive a prenatal diagnosis of Trisomy 13 or 18 by providing up-to-date written resources and connecting them with support groups for parents who have received a similar diagnosis. Our study found that involving genetic counselors in the prenatal care of these patients is likely beneficial. [ABSTRACT FROM AUTHOR]

Objective Trisomies 13 and 18 are among themost common autosomal aneuploidies associated with high mortality rates. Conventional management strategies offer to limit interventional support; however, some of the recent studies suggest that intervention does make a difference in terms of survival. Study Design A retrospective cohort study was performed between January 1996 and January 2016, covering all cases with such trisomies. A total of 69 cases were reviewed for clinical aspects, outcome, and management strategies. Results In almost all pregnancies with follow-up, at least one indication present for invasive testing (54/55). Invasive testing was not performed in 18.5% of such cases. All parents opted for termination in cases with prenatal diagnosis. None of the liveborns had prenatal diagnoses, thus, neonatal resuscitation and intensive care unit admission were not withheld in such infants. Major intervention was done in only one patient with full trisomy 13. Median survival for infants with full trisomies 13 and 18 was 36 and 60 days, respectively. Almost half the patients died within 1 month. Conclusion To which extent the major interventions should be withheld is an issue of debate in managing such infants; however, current approaches are subject to change, given the technological advances. [ABSTRACT FROM AUTHOR]

Objective: To examine the diagnostic accuracy of a previously developed model for the first-trimester combined test in screening for trisomies 21, 18 and 13.Methods: This was a prospective validation study of screening for trisomies 21, 18 and 13 by assessment of a combination of maternal age, fetal nuchal translucency, fetal heart rate and serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation in 108 982 singleton pregnancies undergoing routine care in three maternity hospitals. A previously published algorithm was used to calculate patient-specific risks for trisomy 21, 18 and 13 in each patient. The detection rate (DR) and false-positive rate (FPR) at estimated risk cut-offs from 1 in 2 to 1 in 1000 were determined. The proportions of trisomies detected were compared to their expected values in different risk groups.Results: In the study population, there were 108 112 (99.2%) cases with normal fetal karyotype or birth of a phenotypically normal neonate and 870 (0.8%) cases with abnormal karyotype, including trisomy 21 (n = 432), trisomy 18 (n = 166), trisomy 13 (n = 56), monosomy X (n = 63), triploidy (n = 35) or other aneuploidy (n = 118). The screen-positive rates, standardized according to the maternal age distribution in England and Wales in 2011, of fetuses with abnormal or normal karyotype were compatible with those predicted from the previous model; at a risk cut-off of 1 in 100, the FPR was about 4% and the DRs for trisomies 21, 18 and 13 were 90%, 97% and 92%, respectively. There was evidence that the algorithm overestimated risk. This could, to some degree, reflect under-ascertainment in pregnancies ending in miscarriage or stillbirth.Conclusion: In a prospective validation study, the first-trimester combined test detected 90%, 97% and 92% of trisomies 21, 18 and 13, respectively, as well as > 95% of cases of monosomy X and triploidies and > 50% of other chromosomal abnormalities, at a FPR of 4%. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

There are few reports on the prognosis of prenatally diagnosed trisomy 13 in relation to postnatal management. The aim of this study was to report on the prenatal and postnatal outcomes and postnatal management of trisomy 13 fetuses that were prenatally diagnosed at our center between 2003 and 2015. The data were retrospectively reviewed from medical records. Of the 31 cases of trisomy 13, 12 patients were diagnosed before 22 weeks of gestation, and 19 were diagnosed at or after 22 weeks of gestation. Nine families opted for termination of the pregnancy, 14 fetuses died, and 8 were born alive. Aggressive treatment was requested in two of the live births, with one patient achieving long-term survival (7 years). The other died during infancy (Day 61). One out of four who received palliative treatment is alive at two years of age with only nutrition supplementation. These three patients who achieved neonatal survival had few structural anomalies. Fetal death and early neonatal death are common in trisomy 13; however, fetuses that receive medical treatment for cases without major ultrasound abnormalities may achieve neonatal survival. Therefore, it is useful to provide comprehensive information, including precise ultrasound findings and treatment options, to parents with trisomy 13 fetuses during genetic counseling. [ABSTRACT FROM AUTHOR]

Prenatal ultrasound is a powerful tool to detect structural abnormalities associated with the fetuses in trisomy 13 pregnancies. This article provides a comprehensive review of the prenatal sonographic markers of trisomy 13 in the first trimester, including fetal nuchal translucency thickness, fetal heart rate, fetal nasal bone, fetal tricuspid regurgitation, ductus venous flow, fetal crown-rump length, fetal trunk and head volume, fetal frontomaxillary facial angle, gestational sac volume and umbilical cord diameter, along with biochemical markers such as maternal serum free β-human chorionic gonadotropin, maternal serum pregnancy-associated plasma protein-A, maternal serum placental growth factor, and the fetal and total cell-free DNA concentration in the maternal circulation.

Counseling parents of a fetus with trisomy 13 mosaicism remains difficult because of the phenotypic variability associated with the condition; some patients exhibit the typical phenotype of complete trisomy 13 with neonatal death, while others have few dysmorphic features and prolonged survival. This article provides a comprehensive review of the prenatal diagnosis and genetic counseling for mosaic trisomy 13, including confined placental mosaicism 13, mosaic trisomy 13 diagnosed at amniocentesis, and phylloid hypomelanosis in association with mosaic trisomy 13.

Prenatal ultrasound is a powerful tool for the detection of structural abnormalities of fetuses in trisomy 13 pregnancies. This article provides a comprehensive review of the prenatal sonographic features of trisomy 13 fetuses in the second and third trimesters, including cystic hygroma and nuchal edema, congenital heart defects, hydrops fetalis, omphalocele, diaphragmatic hernia, urinary tract abnormalities, and abnormal extremities and polydactyly.

It has been shown that in non-invasive prenatal testing (NIPT) there is a small chance of a false-positive or false-negative result. This is partly due to the fact that the fetal cell-free DNA present in maternal plasma is derived from the cytotrophoblast of chorionic villi (CV), which is not always representative for the fetal karyotype due to chromosomal mosaicism. Therefore, a positive NIPT result should always be confirmed with invasive testing, preferably amniocentesis, in order to investigate the fetal karyotype. However, since this invasive test can only be safely performed after 15.5 weeks of gestation while NIPT can be done from the 10thweek of gestation, this potentially means an unacceptable long waiting time for the prospective parents to receive a definitive result. Based on our experience with cytogenetic investigations in CV and the literature, we determined whether CV sampling may be appropriate for confirmation of an abnormal NIPT result. [ABSTRACT FROM PUBLISHER]

The diagnosis of trisomy 13 has been considered incompatible with life. Trisomy 13 is associated with a pattern of congenital anomalies and mental disabilities that make caring for these infants a challenge for both the family and health care professionals. The clinical management of trisomy 13 varies based on the organ systems involved. The current standard of care has been withholding intensive support and providing comfort care. Recent literature suggests there are improved outcomes in infants who receive intensive care at birth. In addition, case reports evaluating older children with trisomy 13 report that, although there are significant intellectual and psychomotor disabilities, these children do meet developmental milestones such as smiling in response to parents, sitting unassisted, and walking with a walker. This case review will include a discussion of the clinical course of an infant born with mosaic trisomy 13 where the parents requested intensive care. [ABSTRACT FROM AUTHOR]

Objective: To develop a microarray-based method for noninvasive prenatal testing (NIPT) and compare it with next-generation sequencing. Methods: Maternal plasma from 878 pregnant women, including 187 trisomy cases (18 trisomy 13, 37 trisomy 18, 132 trisomy 21), was evaluated for trisomy risk. Targeted chromosomes were analyzed using Digital Analysis of Selected Regions (DANSR™) assays. DANSR products were subsequently divided between two DNA quantification methods: microarrays and next-generation sequencing. For both microarray and sequencing methodologies, the Fetal-Fraction Optimized Risk of Trisomy Evaluation (FORTE™) algorithm was used to determine trisomy risk, assay variability across samples, and compute fetal fraction variability within samples. Results: NIPT using microarrays provided faster and more accurate cell-free DNA (cfDNA) measurements than sequencing. The assay variability, a measure of variance of chromosomal cfDNA counts, was lower for microarrays than for sequencing, 0.051 versus 0.099 (p < 0.0001). Analysis time using microarrays was faster, 7.5 versus 56 h for sequencing. Additionally, fetal fraction precision was improved 1.6-fold by assaying more polymorphic sites with microarrays (p < 0.0001). Microarrays correctly classified all trisomy and nontrisomy cases. Conclusions: NIPT using microarrays delivers more accurate cfDNA analysis than next-generation sequencing and can be performed in less time. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article described a study that evaluated the impact of screening for Down's syndrome on the prevalence of live births and antenatal diagnoses of Edwards and Patau syndrome. As mentioned, the study concluded that around 700 women per year had a pregnancy with Edwards or Patau syndrome, with over 90% of these pregnancies were detected antenatally, with the increased use of first trimester screening for Down's syndrome resulting in the reduction in the mean gestational age at diagnosis.

OBJECTIVE: Little is known about how very low birth weight (VLBW) affects survival and morbidities among infants with trisomy 13 (T13) or trisomy 18 (T18). We examined the care plans for VLBW infants with T13 or T18 and compared their risks of mortality and neonatal morbidities with VLBW infants with trisomy 21 and VLBW infants without birth defects. METHODS: Infants with birth weight 401 to 1500 g born or cared for at a participating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network during the period 1994-2009 were studied. Poisson regression models were used to examine risk of death and neonatal morbidities among infants with T13 or T18. RESULTS: Of 52 262 VLBW infants, 38 (0.07%) had T13 and 128 (0.24%) had T18. Intensity of care in the delivery room varied depending on whether the trisomy was diagnosed before or after birth. The plan for subsequent care for the majority of the infants was to withdraw care or to provide comfort care. Eleven percent of infants with T13 and 9% of infants with T18 survived to hospital discharge. Survivors with T13 or T18 had significantly increased risk of patent ductus arteriosus and respiratory distress syndrome compared with infants without birth defects. No infant with T13 or T18 developed necrotizing enterocolitis. CONCLUSIONS: In this cohort of liveborn VLBW infants with T13 or T18, the timing of trisomy diagnosis affected the plan for care, survival was poor, and death usually occurred early. [ABSTRACT FROM AUTHOR]

Background: The role of three-dimensional ultrasound in the prenatal diagnosis of orofacial clefts is increasing in recent time. Materials and Methods: We obtained three-dimensional data sets of the fetal face from 100 low-risk and 50 high-risk first-trimester fetuses to evaluate the offline reformatting accuracy of the retronasal triangle (RNT) using a novel reslicing technique. Results: Adequate volume data sets for offline analysis were captured in 98% of cases. The RNT view was reformatted in 96% of cases by offline analysis. The secondary palate could be assessed in 93% by offline analysis and an abnormal RNT in the coronal plane was detected in 2 cases of lethal aneuploidy. The false-positive rate was 1.33% in the two studied groups. Conclusion: Abnormal RNT seems to be a valuable ultrasound marker for the early diagnosis of facial clefting. This novel reslicing technique has proven to be easy, fast and accurate, which suggest that this technology could be included in daily practice and integrated with other applications such as multiplanar mode and volume NT. Prospective studies are needed to confirm these promising results and to demonstrate if these diagnostic armamentarium tools will lead to a diagnostic enhancement of cleft lip and palate in early pregnancy. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The 1997 discovery of free fetal DNA in maternal plasma launched clinical researchers' efforts to establish a reliable method for non-invasive prenatal testing for fetal genetic conditions. Various methods, including, but not limited to, massively parallel sequencing (MPS) and selective analysis of cell-free fetal DNA in maternal plasma, have recently been developed as highly sensitive and specific noninvasive screening tools for common fetal chromosome aneuploidies. Incorporating these new noninvasive technologies into clinical practice will impact the current prenatal screening paradigm for fetal aneuploidy, in which genetic counseling plays an integral role. The National Society of Genetic Counselors (NSGC) currently supports Noninvasive Prenatal Testing/Noninvasive Prenatal Diagnosis (NIPT/NIPD) as an option for patients whose pregnancies are considered to be at an increased risk for certain chromosome abnormalities. NSGC urges that NIPT/NIPD only be offered in the context of informed consent, education, and counseling by a qualified provider, such as a certified genetic counselor. Patients whose NIPT/NIPD results are abnormal, or who have other factors suggestive of a chromosome abnormality, should receive genetic counseling and be given the option of standard confirmatory diagnostic testing. [ABSTRACT FROM AUTHOR]

Coexistence of XX/XY sex mosaicism and autosomal trisomy in prenatal diagnosis is particularly rare. Herein, we report the first, to our knowledge, case of a fetus with cyclopia, ambiguous genitalia and a 47,XX,+13,inv9[47]/47,XY,+13[13] karyotype detected at 13 weeks of gestation after chorionic villus sampling. Molecular analysis after prenatal diagnosis suggests that this is a case of sex mosaicism coexisting with trisomy 13, rather than chimera. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives In Denmark a new national guideline for prenatal screening and diagnosis was issued in 2004 according to which all pregnant women should be offered a first-trimester combined risk assessment for trisomy 21 (T21). The aim of this study was to investigate whether the new screening strategy for T21 has changed the gestational age at which trisomy 18 (T18) and trisomy 13 (T13) are diagnosed prenatally, and the number of infants born with T18 or T13. Methods We collected from the Danish Cytogenetic Central Register information on all prenatal and postnatal chromosome analyses for T18 or T13, registered from 1997 to 2007. Information on first-trimester screening results was collected from each department of obstetrics and gynecology performing the nuchal translucency scans. The cut-off used for referral to invasive diagnostic testing for T21 and for T18/T13 was 1 : 300 and 1 : 150 at screening, respectively. Results In total, there were 435 cases with T18 and 168 cases with T13 between 1997 and 2007 in Denmark. The estimated incidence of T18 and T13 at the time of delivery was calculated as 2.5 and 1.6 per 10 000 deliveries, respectively. The number (proportion) of cases diagnosed before week 18 increased significantly, from 63 (59.4%) in 1997 and 1998 to 90 (80.4%) in 2006 and 2007 ( P < 0.001). In addition, the number of T18 and T13 cases diagnosed prenatally after week 22 or postnatally decreased significantly, from 34 (32.1%) in 1997 and 1998 to seven (6.3%) in 2006 and 2007 ( P < 0.0001). For women participating in first-trimester risk assessment in 2006 and 2007, the detection rate of T18 and T13 was 78.8% (95% CI, 71.0-86.7%). Conclusion The number of T18 and T13 fetuses diagnosed before week 18 increased significantly after the introduction of a combined first-trimester screening strategy for T21 in Denmark. In addition, the total number of fetuses diagnosed late in pregnancy and infants born with T18 or T13 decreased significantly. The national detection rate for T18 and T13 in the first trimester is comparable with detection rates found in modeled datasets and other prospective studies. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To describe pregnancy outcomes of fetuses affected by trisomies 13 and 18 following prenatal diagnosis and a decision to continue the pregnancy. Material and Methods: A single-center, retrospective study of 34 cases with a diagnosis or strong suspicion of trisomy 13 or 18. Results: Fourteen of 34 (41%) families chose to continue the pregnancy after a diagnosis of trisomy 13 or 18 was made. Nine fetuses subsequently died in utero (IUD). No prenatal signs were predictive of IUD. There were no intrapartum deaths. All 4 live-born babies were delivered vaginally; 2 died immediately after birth in the labor ward whilst 2 were transferred to the neonatal unit, dying at 10 and 11 days, respectively. Discussion: Couples should be counseled that the precise outcome of trisomy 13 or 18 is unpredictable, and they should receive multidisciplinary support. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]