HBR Article : How AI Will Transform Project Management
Only 35% of projects today are completed successfully. One reason for this disappointing rate is the low level of maturity of technologies available for project management. This is about to change. Researchers, startups, and innovating organizations, are beginning to apply AI, machine learning, and other advanced technologies to project management, and by 2030 the field will undergo major shifts. Technology will soon improve project selection and prioritization, monitor progress, speed up reporting, and facilitate testing. Project managers, aided by virtual project assistants, will find their roles more focused on coaching and stakeholder management than on administration and manual tasks. The author show how organizations that want to reap the benefits of project management technologies should begin today by gathering and cleaning project data, preparing their people, and dedicating the resources necessary to drive this transformation.
Need to Know: Artificial Intelligence| PMI
Applications of AI in Project Management
Your AI-powered assistant for all things Project Management. PMOtto integrates GPT-4 with a comprehensive dataset of project management resources. Created by Ricardo Vargas and Antonio Nieto-Rodriguez.
Video : How AI will transform Project Management
The PMI Portugal Conference ART & SCIENCE of PROJECT LEADERSHIP took place on the 12th and 13th October 2023 in Lisbon, and it was magnificent!We’re privileged to listen to Ricardo Vargas, with whom the PMI Portugal partners for many years. Ricardo shared his perspective on how AI will transform Project Management.
HBR Article : The Opportunities at the Intersection of AI, Sustainability, and Project Management
There are unprecedented opportunities at the intersection of AI, project management, and sustainability. Unfortunately, without proper execution, projects to implement AI come with complexities, costs and a carbon footprint that undermine sustainability goals. It is essential for project managers to learn to implement “green algorithms,” specialized AI constructs designed to both enhance operational efficiency and prioritize sustainability. A five-step framework of defining sustainability objectives, centralizing data, customizing algorithms, pilot testing, and full-scale implementation can guide project managers and leaders as they deploy green algorithms effectively.
Genetic assessment following increased nuchal translucency and normal karyotype
OBJECTIVE: The objective of this study was to assess the first formal approach for monitoring genetic/developmental syndromes associated with the presence of an increased nuchal translucency (NT) thickness (>3 mm) in the first trimester of pregnancy. METHODS: Multiple technologies-a DNA chip using the APEX technology, qPCR, microfluidic PCR, and sequencing-were applied to assay 310 mutations across five conditions-Noonan syndrome, congenital adrenal hyperplasia, spinal muscular atrophy (SMA), DiGeorge syndrome, and Smith-Lemli Opitz syndrome. RESULTS: We report the results of assessing the first 120 patients in which 8 cases of Noonan syndrome were detected as well as an unusually high rate of heterozygosity for SMA. CONCLUSION: While testing for Noonan syndrome in association with increased NT appears warranted, the reported association of the remaining four genetic syndromes is likely to be weak and possibly insignificant.
Analysis of cystic hygroma diagnosed in the first trimester: Single-center experience
OBJECTIVE: To evaluate the obstetric outcomes of fetuses with cystic hygroma other than karyotype abnormalities and structural malformations. MATERIAL AND METHODS: We conducted a retrospective study based on the review of medical records of pregnant women in whom ultrasonographic diagnosis of fetal cystic hygroma was established in the first trimester from January 2014 to October 2018. All patients were offered genetic counselling and prenatal invasive diagnostic procedures to obtain fetal karyotype. For ongoing pregnancies fetal echocardiography and detailed second trimester sonographic anomaly screening was performed by a perinatologist/pediatric cardiologist. The demographic characteristics of the women and the results of the karyotype analysis were obtained from the database of our hospital and correlated with the obstetric outcomes. RESULTS: Within a five-year period, there were 106 cases of fetal cystic hygroma. Of those, fetal cardiac malformations were detected in four and micrognathia in one fetus. Eighty-five women underwent fetal invasive procedures and karyotype abnormalities were detected in 52 of the cases. Fetal outcomes of 33 cases with normal karyotype and 21 cases in whom karyotyping analysis were not performed due to patient refusal were enrolled into the study. Obstetric outcomes of 21 women who refused karyotyping consisted of 13 livebirths, seven missed abortions, and one fetal death, whereas those of 33 women with normal karyotype were; 12 livebirths, 12 missed abortions, two hydrops fetalis, and five fetal deaths. Nineteen of 33 fetuses with a normal karyotype and eight of 21 fetuses in whom karyotyping was not performed were terminated. CONCLUSION: The presence of cystic hygroma carries a high risk for fetal karyotype abnormalities and cardiac malformations. The postnatal outcomes of the fetuses with cystic hygroma appeared to be correlated with the absence of structural malformations and karyotype abnormalities.
Analysis of cystic hygroma diagnosed in the first trimester
Journal of the Turkish German Gynecological Association
Incidence of major structural cardiac defects associated with increased nuchal translucency but normal karyotype
OBJECTIVE: To examine the association between increased nuchal translucency thickness and major cardiac defects in chromosomally normal fetuses. SETTING: Tertiary referral unit for fetal medicine and fetal cardiology. METHODS: During a 4-year period (January 1997 to January 2001), detailed echocardiography was performed in 1319 chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. The incidence of major cardiac defects was examined in relation to the fetal NT at the 10-14-week scan. RESULTS: Major cardiac defects were diagnosed in 60 (4.5%) of the 1319 fetuses. In fetuses with a nuchal translucency thickness in the range of 2.5-3.4 mm, the incidence of major cardiac defects was 2.5% (18/722; 95% confidence interval, 1.5-3.9) and in those with a nuchal translucency thickness > or =3.5 mm, it was 7% (42/597; 95% confidence interval, 5.1-9.4). CONCLUSION: Specialist echocardiography is indicated in all fetuses with increased nuchal translucency thickness because, in such fetuses, the incidence of major cardiac defects is substantially higher than in pregnancies with maternal diabetes, family history and exposure to drugs, where fetal echocardiography is widely considered to be necessary.
Ultrasound in Obstetrics & Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology
First-trimester ultrasound diagnosis of skeletal dysplasia associated with increased nuchal translucency thickness
A series of five cases of skeletal dysplasia is reported in which the diagnosis was reached at the 11-14-week routine ultrasound examination in our referral center. All five cases had increased nuchal translucency thickness (NT) associated with bone abnormalities. We review the current literature on skeletal dysplasia in the first trimester of pregnancy associated with increased NT.
Long-term outcome in apparently healthy children with increased nuchal translucency in the first trimester screening
INTRODUCTION: Increased nuchal translucency is known to be associated with chromosomal and structural defects and genetic syndromes. Little is known about the overall long-term outcome of euploid children after increased nuchal translucency. The aims of this study were to assess the additional structural defects diagnosed after discharge from the delivery hospital and the long-term overall outcome of euploid children after increased nuchal translucency and normal second trimester anomaly scan. MATERIAL AND METHODS: All children from singleton euploid pregnancies during 2002-2007 with increased nuchal translucency in the first trimester screening, normal second trimester anomaly scan, and discharged as apparently healthy were included. Data on the structural defects and genetic disorders diagnosed until 2012 were retrieved from hospital databases and national registers. Previously published data of structural defects diagnosed after birth but before discharge and of severe neurodevelopmental impairment and genetic syndromes was added. RESULTS: The cohort included 733 children. During the follow-up time (mean 6.5 years), major structural defects were observed in 10 (1.4%), genetic disorders in two (0.3%), and minor defects in 23 (3.1%) children. In addition, there were 42 previously published major structural defects and major neurodevelopmental impairment or genetic disorders. Adding these results together, major health problems were detected in 54 (7%) euploid children with increased fetal nuchal translucency and normal findings in second trimester anomaly scan. CONCLUSION: Although only few additional major structural defects are diagnosed during the follow-up after increased fetal nuchal translucency, 7% of fetuses assumed to be healthy after second trimester anomaly scan have a major health impairment.
Acta Obstetricia Et Gynecologica Scandinavica
Äyräs et al. - 2016 - Long-term outcome in apparently healthy children w.pdf
Adverse pregnancy outcome in fetuses with early increased nuchal translucency: prospective cohort study
OBJECTIVES: An increased nuchal translucency (NT) thickness of ≥ 3.5 mm is a well-established marker for congenital anomalies and adverse pregnancy outcome between 11 and 14 weeks' gestation, but little is known about its performance as a screening tool before 11 weeks. We aimed to investigate, in a prospective setting, whether fetuses with increased NT before 11 weeks are at risk for adverse pregnancy outcome. METHODS: This was a prospective cohort study including pregnant women with a viable fetus with NT ≥ 2.5 mm and a crown-rump length (CRL) < 45 mm. All included women were referred to our fetal medicine unit (FMU) and scheduled for a follow-up scan where the NT was remeasured after 1 week when the CRL was > 45 mm. Two groups were evaluated: cases with a normalized NT (< 3.5 mm) and cases with persistently increased NT (≥ 3.5 mm). The cases were monitored until 4 weeks after delivery. The main outcome was a composite adverse outcome of aneuploidy, other genetic disorders, structural anomalies and pregnancy loss. We performed subgroup analyses of NT thickness at inclusion and normalized or persistently increased NT at follow-up. RESULTS: The study included 109 cases, of which 39 (35.8%) had an adverse pregnancy outcome. Of these, 64.1% (25/39) were aneuploid, corresponding to 22.9% (25/109) of the total study population. In the subgroups of NT thickness at inclusion of 2.5-3.4 mm, 3.5-4.4 mm and ≥ 4.5 mm, an adverse outcome was reported in 22.0% (9/41), 40.0% (18/45) and 52.2% (12/23), respectively. In fetuses with a normalized NT and without ultrasound abnormalities at the follow-up scan, the incidence of adverse outcome was 8.5% (5/59), of which 5.1% (3/59) cases were aneuploid. CONCLUSIONS: Fetuses with an early increased NT thickness are at considerable risk of an adverse pregnancy outcome, even if the NT normalizes after 11 weeks. Not all congenital anomalies can be diagnosed with routine first-trimester screening, such as non-invasive prenatal testing and/or a first-trimester anomaly scan. Therefore, expectant parents should always be referred to a FMU for detailed ultrasonography. Invasive prenatal testing should be offered if an increased NT of ≥ 2.5 mm is observed before 11 weeks' gestation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Adverse pregnancy outcome in fetuses with early increased nuchal translucency
Bet et al. - 2024 - Adverse pregnancy outcome in fetuses with early in.pdf
Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis
OBJECTIVE: To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first-trimester ultrasound. METHODS: This was a systematic review conducted in accordance with PRISMA criteria. We searched PubMed, Ovid MEDLINE and Web of Science for studies published between January 2009 and January 2015 that described CNVs in fetuses with increased NT, usually defined as ≥ 3.5 mm, and normal karyotype. Search terms included: fetal or prenatal, nuchal translucency or cystic hygroma or ultrasound anomaly, array comparative genomic hybridization or copy number variants, with related search terms. Risk differences were pooled to estimate the overall and stratified microarray incremental yield using RevMan. Quality assessment of included studies was performed using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS: Seventeen studies met the inclusion criteria for analysis. Meta-analysis indicated an incremental yield of 5.0% (95% CI, 2.0-8.0%) for the detection of CNVs using microarray when pooling results. Stratified analysis of microarray results demonstrated a 4.0% (95% CI, 2.0-7.0%) incremental yield in cases of isolated NT and 7.0% (95% CI, 2.0-12.0%) when other malformations were present. The most common pathogenic CNVs reported were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion and 12q21q22 deletion. The pooled prevalence for variants of uncertain significance was 1%. CONCLUSION: The use of genomic microarray provides a 5.0% incremental yield of detecting CNVs in fetuses with increased NT and normal karyotype.
Genomic microarray in fetuses with increased nuchal translucency and normal karyotype
Grande et al. - 2015 - Genomic microarray in fetuses with increased nucha.pdf
Ngo et al. - 2007 - First-trimester ultrasound diagnosis of skeletal d.pdf
Ghi et al. - 2001 - Incidence of major structural cardiac defects asso.pdf
Pergament et al. - 2011 - Genetic assessment following increased nuchal tran.pdf
Late onset of large benign ductus arteriosus aneurysm presented with increased nuchal translucency and cystic hygroma at first trimester Down syndrome screening
OBJECTIVE: Fetal ductus arteriosus aneurysm (DAA) is a rare but potentially risky congenital heart disease. It is often not diagnosed until the third trimester because of its asymptomatic nature and late onset. In rare occasions, DAA may result in serious complications; therefore, prenatal diagnosis is helpful. CASE REPORT: Herein, we report the case of a foetus with cystic hygroma and increased nuchal translucency in the first trimester (but regressed at 20-week anomalous scan). Karyotyping indicated a 46 XY genotype. A large vascular mass was noted at the apex of the left lung by Doppler ultrasound at 38 weeks of gestation, with a diameter of 12.5 mm. After birth, echocardiography showed a patent ductus arteriosus with aneurysmal dilatation (17 mm as the largest diameter); thus, DAA was impressed. Chest computed tomography and three-dimensional angiography confirmed the large aneurysmal dilatation of the ductus arteriosus with a closed end at the pulmonary arterial side. CONCLUSION: The male infant survived, but presented mild respiratory distress at birth. He was discharged at 24 days of age. At that time, DAA had regressed partially (diameter of 8.5 mm and much less blood flow), and it fully regressed at 40 days of age.
Taiwanese Journal of Obstetrics & Gynecology
Tsai et al. - 2016 - Late onset of large benign ductus arteriosus aneur.pdf
Fetal cystic hygroma in the first trimester led to diagnosis of partial trisomy 22
Partial trisomy 22 is a rare condition that is found in live birth. In most cases, diagnosis of partial trisomy 22 was made after birth. Herein, we report a prenatal diagnosis of fetal partial trisomy 22 in a 28-year-old pregnant woman presented with fetal cystic hygroma. Structural abnormalities were detected at 16 weeks of gestation: left cleft lip and ventricular septal defect. The G-banding karyotype analysis and fluorescence in situ hybridization showed partial trisomy 22. It is recommended that pregnant women with fetal anomalies should have prenatal genetic diagnosis to ascertain whether the fetus has partial trisomy 22 or other rare chromosomal abnormalities.
Antenatal screening for chromosomal abnormalities
Screening for chromosomal disorders, especially for trisomy 21, has undergone a number of changes in the last 50 years. Today, cell-free DNA analysis (cfDNA) is the gold standard in screening for trisomy 21. Despite the advantages that cfDNA offers in screening for common trisomies, it must be recognized that it does not address many other chromosomal disorders and any of the structural fetal anomalies. In the first trimester, the optimal approach is to combine an ultrasound assessment of the fetus, which includes an NT measurement, with cfDNA testing. If fetal structural defects are detected or if the NT thickness is increased, an amniocentesis or a CVS with at least chromosomal microarray should be offered.
Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma
It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.
Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas
Vascular Endothelial Growth Factor Receptor-2
Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma
BACKGROUND: The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. METHODS: Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. RESULTS: The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. CONCLUSION: Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.
Prenatal Genetic Diagnosis of Fetal Cystic Hygroma: A Retrospective Single-Center Study from China
Fetal cystic hygroma (CH) is associated with poor prognosis and chromosomal anomalies. Recent studies have suggested that the genetic background of affected fetuses is essential for predicting pregnancy outcomes. However, the detection performance of different genetic approaches for the etiological diagnosis of fetal CH remains unclear. In this study, we aimed to compare the diagnostic efficiency of karyotyping and chromosomal microarray analysis (CMA) in a local fetal CH cohort, and tried to propose an optimized testing strategy that may help improve the cost-effectiveness of disease management. We reviewed all pregnancies that underwent invasive prenatal diagnosis between January 2017 and September 2021 at one of the largest prenatal diagnostic centers in Southeast China. We collected cases identified by the presence of fetal CH. Prenatal phenotypes and laboratory records of these patients were audited, collated, and analyzed. The detection rates of karyotyping and CMA were compared, and the concordance rate of these two methods was calculated. A total of 157 fetal CH cases were screened from 6,059 patients who underwent prenatal diagnosis. Diagnostic genetic variants were identified in 44.6% (70/157) of the cases. Karyotyping, CMA, and whole-exome sequencing (WES) identified pathogenic genetic variants in 63, 68, and 1 case, respectively. The Cohen's κ coefficient between karyotyping and CMA was 0.96, with a concordance of 98.0%. Of the 18 cases in which cryptic copy number variants <5 Mb were detected by CMA, 17 were interpreted as variants of uncertain significance, and the remaining cases were interpreted as pathogenic. Trio exome sequencing revealed a pathogenic homozygous splice site mutation in the PIGN gene in a case undiagnosed by CMA and karyotyping. Our study demonstrated that chromosomal aneuploidy abnormalities are the main genetic cause of fetal CH. Based on this, we recommend karyotyping combined with rapid aneuploidy detection as a first-tier approach for the genetic diagnosis of fetal CH. WES and CMA could improve the diagnostic yield when routine genetic tests fail to determine the cause of fetal CH.
Prenatal Genetic Diagnosis of Fetal Cystic Hygroma
Zhou et al. - 2022 - Prenatal Genetic Diagnosis of Fetal Cystic Hygroma.pdf
Protein Tyrosine Phosphatase, Non-Receptor Type 11
How necessary is to analyze PTPN11 gene in fetuses with first trimester cystic hygroma and normal karyotype?
Cystic hygroma (CH) is a vascular-lymphatic malformation and can occur either as an isolated finding or as a part of a syndrome. The incidence of CH is about 1:1000-1:6000 births. Ultrasonographic diagnosis of CH is usually obtained in the first trimester, and the lesion can appear in septated or non-septated forms. Increased nuchal translucency and CH have been associated with a wide range of structural and genetic abnormalities. Most of CHs are associated with a number of chromosomal abnormalities especially Trisomy 21, 13, 18 and Turner syndrome. Besides, the associations between CH and non-chromosomal syndromes were also reported and Noonan Syndrome (NS) is one of the leading causes. Approximately 50% of NS cases are caused by mutations in the PTPN11 gene. A novel PTPN11 mutation defined in two separate fetuses with CH and associated with NS phenotype is being reported here.
The Journal of Maternal-Fetal & Neonatal Medicine: The Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
Gezdirici et al. - 2017 - How necessary is to analyze PTPN11 gene in fetuses.pdf
Characteristics and outcome of fetal cystic hygroma diagnosed in the first trimester
OBJECTIVE: The aim of this study was to determine the course of pregnancy and the neonatal outcome of fetuses with cystic hygroma diagnosed at 10-14 weeks' gestation. METHODS: Maternal and fetal data (nuchal translucency, karyotype, pregnancy outcome) in cases of fetal cystic hygroma, admitted or referred to our antenatal diagnostic centre, were prospectively entered into a computer database. Paediatric outcome was analysed when relevant. RESULTS: Some 72 fetuses had cystic hygroma. The mean size of the cystic hygroma was 7.9 mm. Chromosomal abnormalities were present in 52.7% of cases (38/72), including 14 cases (36.8%) of Down syndrome. A total of 34 chromosomally normal pregnancies gave rise to 18 live births (52.9%), with no visible serious structural abnormalities. The outcome of pregnancy was unfavourable (miscarriage, elective termination, serious structural abnormalities) in 77.7% of cases (56/72). The 18 live-born infants were followed up for 17-98 months. Sixteen infants developed normally, while 1 developed Noonan's syndrome and 1 had a urinary tract abnormality (pyelo-ureteral junction; PUJ). CONCLUSION: These data suggest that the prognosis of fetal cystic hygroma detected during the first trimester is poor, and show that sonographic evaluation of fetal nuchal translucency thickness in the first trimester is crucial.
Graesslin et al. - 2007 - Characteristics and outcome of fetal cystic hygrom.pdf
Array comparative genomic hybridization (aCGH)
Fetal Cystic Hygroma Associated with Terminal 2p25.1 Duplication and Terminal 3p25.3 Deletion: Cytogenetic, Fluorescent in Situ Hybridization and Microarray Familial Characterization of Two Different Chromosomal Structural Rearrangements
We report a prenatally diagnosed case of partial trisomy 2p and partial monosomy 3p, resulting from unbalanced translocation (2;3)(p25.1;p25.3) of paternal origin. Parents were non consanguineous Caucasians, with familial history of recurrent miscarriages on the father's side. Detailed sonographic examination of the fetus showed a septated cystic hygroma measuring 6 mm at 13 weeks' gestation. Karyotyping and fluorescent in situ hybridization (FISH) analysis of cultured amniotic fluid cells revealed an unbalanced translocation der(3)t(2;3)(p25.1; p25.3) and apparently balanced inv(3)(p13p25.3) in a fetus. Parental cytogenetic evaluation using karyotyping and FISH analysis showed the presence of both a balanced translocation and a paracentric inversion in father t(2;3) (p25.1;p25.3) inv(3)(p13p25.3). Microarray analysis showed a 11.6 Mb deletion at 3p26.3-p25.3 and duplication of 10.5 Mb at the 2p25.3-p25 region. The duplicated region at 2p25.1p25.3 contains 45 different genes, where 12 are reported as OMIM morbid genes with different phenotypical implications. The deleted region at 3p26.3-p25.3 contains 65 genes, out of which 27 are OMIM genes. Three of these (CNTN4, SETD5 and VHL) were curated by Clingene Dosage Gene Map and were given a high haplo-insufficiency score. Genes affected by the unbalanced translocation could have contributed to some specific phenotypic changes of the fetus in late pregnancy. The application of different cytogenetic methods was essential in our case, allowing the detection of different types of structural chromosomal aberrations and more thorough genetic counseling for future pregnancies.
Fetal Cystic Hygroma Associated with Terminal 2p25.1 Duplication and Terminal 3p25.3 Deletion
Balkan journal of medical genetics: BJMG
First-trimester cystic hygroma: relationship of nuchal translucency thickness and outcomes
OBJECTIVE: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. METHODS: We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. RESULTS: There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29-1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08-1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07-2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15-2.74, P=.01). CONCLUSION: First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase.
Scholl et al. - 2012 - First-trimester cystic hygroma relationship of nu.pdf
Prenatal Ultrasound Evaluation and Outcome of Pregnancy with Fetal Cystic Hygromas and Lymphangiomas
Cystic hygroma is a type of lymphangioma, which is a vascular anomaly associated with lymphatic malformations and formed by fluid accumulation mainly located at the cervi-cofacial and axillary regions. Cystic hygroma is mostly located in the neck (75%), followed by axilla (20%), retroperitoneum and intra-abdominal organs (2%), limbs and bones (2%), and mediastinum (1%). It is often associated with chromosome aneuploidies, hydrops fetalis, and even intrauterine fetal demise. The prognostic factors of the fetal cystic hygroma or lymphan-gioma are chromosome abnormalities, hydrops fetalis, septations, or thickness of the cystic hygroma and are associated with other major malformations. Prenatal managements including ultrasound serial follow-up, magnetic resonance imaging, or even intrauterine injection of sclerosing agents are suggested. For fetus with the risk of airway obstruction at delivery, ex utero intrapartum treatment is also indicated. Detailed prenatal counseling is necessary for better neonatal outcome.
Genetic Burden and Outcome of Cystic Hygromas Detected Antenatally: Results of 93 Pregnancies from a Single Center in the Northern Region of Turkey
OBJECTIVE: Genetic burden, fetal malformations, and fetal outcomes of 93 fetuses with cystic hygroma (CH) are reported from a single center in Turkey. PATIENTS AND METHODS: Pregnancies, having a diagnosis of fetal CH, detected between January 2010 and October 2016, were included in the study except fetuses having increased nuchal translucency. Fetal age/gender, maternal age, the age of pregnancy, types of fetal malformations, karyotype, and outcomes were evaluated. RESULTS: The average gestational age was 16.2 weeks. Nearly 47% of the pregnancies had multiple congenital anomalies, of which 58% had a chromosomal anomaly. Chromosomal anomaly rate was 68.2% in patients with hydrops fetalis. Aneuploidies were major chromosomal defects. All trisomies were of regular type except one with Robertsonian translocation (46, XY, +13, rob[13;14][q10;q10]). Seventy-four percentage pregnancies were terminated due to either fetal/karyotype anomaly. CONCLUSION: Characteristics of fetal CH were similar in different ethnical backgrounds. Aneuploidy is the dominant chromosomal constitution of fetal CH. Little information was known about the genes involved. Gene dosage effect implies that fetal CH is a complex genetic situation involving multiple genes interactions. For proper genetic counseling, each fetus with CH should be karyotyped, and fetal ultrasound examination should be performed. In the case of normal chromosome set, application of aCGH should be considered.
Genetic Burden and Outcome of Cystic Hygromas Detected Antenatally
Retrospective analysis of genetic etiology and obstetric outcome of fetal cystic hygroma: A single-center study
BACKGROUND: Cystic hygroma (CH) is a relatively common observation in prenatal ultrasounds; however, there are few studies about copy number variations (CNVs) of fetuses with CH. METHODS: We performed a retrospective analysis on 40 pregnant patients (out of 8000 pregnant patients) whose fetuses had CH from November 2016 to June 2021. Villus, amniotic fluid, or umbilical cord blood samples were collected, based on the corresponding gestational age, for karyotype analysis and single-nucleotide polymorphism array (SNP-array). RESULTS: Among the 40 fetuses with CH, 16 (40.0%, 16/40) exhibited isolated CH and 24 (60.0%, 24/40) exhibited CH combined with other ultrasound abnormalities. The most common CH-comorbid ultrasound abnormalities observed in this study were congenital heart disease (25.0%, 6/24), thickened nuchal translucency (20.8%, 5/24), and fetal edema (12.5%, 3/24). Karyotype and SNP-array analysis resulted in an overall detection rate of 30.0% (12/40). Karyotype analysis led to the detection of eight cases of pathogenic CNVs, among which 45, X was the most common. In addition to the above pathogenic CNV, four additional cases were detected by SNP-array. There was no significant difference in the observed pathogenic CNVs between isolated CH and CH combined with other ultrasound (31.3% vs 29.2%, P > .99). Karyotype analysis and SNP-array results influence whether parents terminate the pregnancy. When genetic abnormalities are detected in the fetus, the parents often choose to terminate the pregnancy. CONCLUSIONS: Our study emphasizes that genomic examination should be performed on fetuses with CH to confirm the etiology as soon as possible. During genetic counseling, all fetal characteristics should be carefully and comprehensively evaluated.
Retrospective analysis of genetic etiology and obstetric outcome of fetal cystic hygroma
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with increased nuchal translucency, tricuspid regurgitation and abnormal flow in ductus venosus
OBJECTIVE: To examine the association between fetal major heart defects and increased nuchal translucency thickness (NT), tricuspid regurgitation and abnormal flow in the ductus venosus in a large population of singleton pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation. METHODS: This was a retrospective study of prospectively collected data from singleton pregnancies attending for a routine ultrasound scan at 11-13 weeks' gestation, which included examination of fetal anatomy, measurement of NT and assessment of blood flow across the tricuspid valve and in the ductus venosus, according to a standardized protocol. The incidence of fetal NT ≥ 95th and ≥ 99th percentiles, tricuspid regurgitation and reversed a-wave in the ductus venosus in fetuses with and those without a major heart defect was determined and the performance of each marker and their combination in the detection of major heart defects was calculated. RESULTS: The study population of 93 209 pregnancies with no apparent chromosomal abnormality included 211 (0.23%) with a fetal major heart defect and 92 998 morphologically normal neonates. In 113 (53.6%) cases with a major heart defect, the diagnosis was made at the 11-13-week scan, in 82 (38.9%) at the 18-24-week scan, in 10 (4.7%) at the third-trimester scan and in six (2.8%) postnatally. At the 11-13-week scan, we diagnosed all cases of tricuspid or pulmonary atresia and polyvalvular dysplasia, > 90% of cases of hypoplastic left heart syndrome or atrioventricular septal defect, about 60% of complex heart defects and cases of left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), 30-40% of cases of tetralogy of Fallot and arch abnormalities, 25% of tricuspid valve abnormalities and about 15% of cases of transposition of the great arteries, but none of aortic or pulmonary stenosis or common arterial trunk. Fetal NT ≥ 95th or ≥ 99th percentile, tricuspid regurgitation or abnormal ductus venosus flow was observed in 77 (36.5%), 45 (21.3%), 61 (28.9%) and 58 (27.5%) fetuses with a major heart defect, respectively, and in 5678 (6.1%), 857 (0.9%), 1136 (1.2%) and 1644 (1.8%) of those without a heart defect. Any one of NT ≥ 95th percentile, tricuspid regurgitation or abnormal flow in the ductus venosus was found in 117 (55.5%; 95% CI, 48.5-62.3%) fetuses with a heart defect and in 8166 (8.8%; 95% CI, 8.6-9.0%) of those without a heart defect. Any one of NT ≥ 99th percentile or the other two markers was found in 99 (46.9%; 95% CI, 40.0-53.9%) fetuses with a heart defect and in 3517 (3.8%; 95% CI, 3.7-3.9%) of those without a heart defect. CONCLUSION: At 11-13 weeks' gestation, measurement of fetal NT and assessment of flow across the tricuspid valve and in the ductus venosus can lead to early diagnosis of major heart defect. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Diagnosis of major heart defects by routine first-trimester ultrasound examination
Minnella et al. - 2020 - Diagnosis of major heart defects by routine first-.pdf
Prenatal whole-exome sequencing in fetuses with increased nuchal translucency
BACKGROUND: Increased nuchal translucency (NT) is associated with an increased risk for genetic disorders. The aim of this study was to investigate the value of whole-exome sequencing (WES) in detecting genetic abnormalities for fetuses with isolated first-trimester increased NT. METHODS: After the exclusion of aneuploidies and pathogenic copy number variants (CNVs) by quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray analysis (CMA), WES was performed on 63 fetuses with isolated first-trimester increased NT (≥3.5 mm). RESULTS: Overall, WES yielded a 4.8% (3/63) diagnostic rate for fetuses with isolated increased NT. Pathogenic variants were identified in 37.5% (3/8) fetuses that developed additional structural anomalies later in gestation, and no pathogenic variants were detected in increased NT that resolved or remained isolated throughout the pregnancy. CONCLUSION: This study provides powerful evidence to offer prenatal WES for increased NT only when additional abnormalities are present. Early detailed ultrasound to detect emerging anomalies can help physicians offer prenatal WES to fetuses with a greater likelihood of diagnosis.
Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency: systematic review and meta-analysis
OBJECTIVE: To determine the diagnostic yield of exome or genome sequencing (ES/GS) over chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) and no concomitant anomalies. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. PubMed, Scopus and Web of Science were searched for studies describing ES/GS in fetuses with isolated increased NT. Inclusion criteria were: (1) study written in English; (2) more than two fetuses with increased NT > 99th percentile and no concomitant anomalies; and (3) a negative CMA result considered as the reference standard. Only positive variants identified on ES/GS that were classified as likely pathogenic or pathogenic and determined to be causative of the fetal phenotype were considered. Risk was assessed as the pooled effect size by single-proportion analysis using random-effects modeling (weighted by inverse of variance). RESULTS: Eleven studies reporting on the diagnostic yield of ES/GS in fetuses with isolated increased NT > 99th percentile were identified and included 309 cases. All studies were high quality according to Standards for Reporting of Diagnostic Accuracy. Overall, a pathogenic or likely pathogenic variant was identified on ES/GS in 15 fetuses, resulting in a pooled incremental yield of 4% (95% CI, 2-6%). Six (40%) of these fetuses had NT of 5 mm or more. The observed inheritance pattern was autosomal dominant in 12 cases, including four fetuses with Noonan syndrome, autosomal recessive in two cases and X-linked in one case. CONCLUSIONS: There is a 4% incremental diagnostic yield of ES/GS over CMA in fetuses with increased NT > 99th percentile without a concomitant anomaly. It is unclear whether a NT cut-off higher than 3.5 mm may be more useful in case selection for ES/GS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency
Pauta et al. - 2022 - Diagnostic yield of next-generation sequencing in .pdf
Chromosomal microarray in fetuses with increased nuchal translucency
OBJECTIVE: To assess the clinical value of using high-resolution chromosomal microarray (CMA) for the examination of genomic imbalances in prenatal uncultured chorionic villus samples from fetuses with increased nuchal translucency (NT) and a normal quantitative fluorescent polymerase chain reaction (QF-PCR) result, in a clinical setting in which more than 95% of pregnant women receive first-trimester combined screening. METHODS: From January 2013 to July 2014, we included 132 chorionic villus samples from consecutive ongoing pregnancies, with fetal NT ≥ 3.5 mm at 11-13 weeks' gestation, from obstetric units (publicly funded healthcare) in Central and North Denmark Regions. DNA was extracted directly from the samples and examined with QF-PCR (n = 132) and 180 kb oligonucleotide array-based comparative genomic hybridization (n = 94). RESULTS: In 38 cases, aneuploidies for chromosomes 18, 21 or X, or triploidy, were detected by QF-PCR. Among the 94 cases with a normal QF-PCR result, we detected pathogenic copy number variants (CNVs) by CMA in 12 fetuses (12.8% (95% CI, 7.5-21.0%)). In an additional three (3.2%) cases, CNVs with uncertain clinical significance were detected. CONCLUSION: CMA is a valuable diagnostic technique in pregnancies with isolated fetal NT ≥ 3.5 mm.
Lund et al. - 2015 - Chromosomal microarray in fetuses with increased n.pdf
Prognostic value of ultrasound findings of fetal cystic hygroma detected in early pregnancy by transvaginal sonography
OBJECTIVE: To assess the prognostic value of first and early second trimester transvaginal ultrasound findings of fetal cystic hygroma such as volume, presence of septa and associated fetal anomalies or malformations. DESIGN: A prospective study of fetal cystic hygroma volume detected at 10-15 weeks of gestation by transvaginal scan. SUBJECTS: The study comprised a series of 33 cystic hygromas detected throughout the period March 1994 to March 1998 in 1918 pregnant women. METHODS: The volume of the hygroma and the presence of septa and other associated fetal anomalies or malformations were evaluated and correlated with fetal karyotype, persistence of the hygroma and pregnancy outcome. RESULTS: A volume equal to or greater than 75 mm3 revealed a sensitivity of 66.7% [eight of 12 cases; 95% confidence interval (CI), 34.9-90.1%] for the identification of abnormal fetal karyotype, 72.7% (eight of 11 cases; 95% CI, 39.0-90.4%) for the identification of persistence of the hygroma and 90% (nine of 10 cases; 95% CI, 55.5-99.7%) for identification of an unfavorable outcome of pregnancy. Furthermore, the prognostic value of ultrasound in determining pregnancy and fetal outcome were improved by combining data on the volume of the hygroma and the presence of associated anomalies or malformations. CONCLUSIONS: Measuring the volume of a cystic hygroma proves to be a useful ultrasound prognostic indicator in determining the risk of an associated karyotypic abnormality and adverse fetal and pregnancy outcome. However, due to limited sample size, caution is required in interpretation of the data and further studies are needed.
Rosati and Guariglia - 2000 - Prognostic value of ultrasound findings of fetal c.pdf
Prise en charge de l’hyperclarté nucale isolée : enquête auprès des Centres pluridisciplinaires de diagnostic prénatal
Résumé Objectif La stratégie de prise en charge dans les situations d’hyperclarté nucale (HCN) isolée du premier trimestre avec un caryotype et une Analyse chromosomique sur puce à ADN (ACPA) normaux n’est pas consensuelle. L’objectif est de réaliser un état des lieux de la prise en charge des HCN au premier trimestre au sein des Centres pluridisciplinaires de diagnostic prénatal (CPDPN) de France. Méthodes Nous avons réalisé une enquête descriptive multicentrique entre septembre 2021 et octobre 2021 auprès des 46 CPDPN de France. Résultats Le taux de réponse était de 56,5 % (n = 26/46). Le seuil de clarté nucale à partir duquel un prélèvement ovulaire pour le bilan génétique est réalisé est de 3,0mm dans 23,1 % des centres (n = 6/26) et de 3,5mm dans 76,9 % des centres (n = 20/26). Une ACPA est réalisée seule dans 26,9 % des centres (n = 7/26), tandis que 7,7 % des centres (n = 2/26) ne réalisent pas d’ACPA. La première échographie de référence est réalisée entre 16 et 18 SA dans 88,5 % des centres (n = 23/26), alors qu’elle n’est pas réalisée avant 22 SA dans 11,5 % des centres (n = 3/26). Une échocardiographie fœtale est proposée systématiquement dans 73,1 % des centres (n = 19/26). Conclusion Il existe une hétérogénéité dans la prise en charge des HCN au premier trimestre. Le seuil d’HCN à partir duquel un prélèvement ovulaire est proposé est variable entre 3,0mm ou 3,5mm selon les centres. L’ACPA et l’échographie morphologique précoce entre 16 et 18 SA ne sont pas systématiquement réalisées, en dépit des données actuelles suggérant leur intérêt. Objectives The management for isolated increased nuchal translucency (NT) in the first trimester with a normal karyotype and normal Chromosomal Microarray Analysis (CMA) is not consensual. The aim was to perform a survey among the Pluridisciplinary Centers for Prenatal Diagnosis (CPDPN) in France regarding their management of increased NT in the first trimester. Methods We conducted a multicenter descriptive survey between September 2021 and October 2021 among the 46 CPDPNs of France. Results The response rate was 56.5% (n = 26/46). The NT thickness threshold for which invasive diagnosis testing is performed is 3.0mm in 23.1% of centers (n = 6/26) and 3.5mm in 76.9% of centers (n = 20/26). A CMA was performed alone in 26.9% of centers (n = 7/26) while 7.7% of centers (n = 2/26) did not perform a CMA. The gestational age for the first reference ultrasound scan was 16 to 18 WG in 88.5% of centers (n = 23/26), while it was not performed before 22 WG in 11.5% of centers (n = 3/26). Fetal echocardiography is proposed systematically in 73.1% of centers (n = 19/26). Conclusion There is heterogeneity in the management of increased NT in the first trimester among the CPDPNs in France. In case of increased NT on first trimester ultrasound scan, the NT thickness threshold for which invasive diagnosis testing is performed varies from 3.0 mm or 3.5mm depending on the center. Moreover, CMA and early reference morphological ultrasound scan between 16 and 18 WG were not systematically performed, despite the current data suggesting their interest.
Prise en charge de l’hyperclarté nucale isolée
Gynécologie Obstétrique Fertilité & Sénologie
De Vriendt et al. - 2023 - Prise en charge de l’hyperclarté nucale isolée e.pdf
716 Outcomes from a 15 Year Review of Cystic Hygroma
SMFM 44th Annual Meeting: The Pregnancy Meeting Publication of this Abstract book is supported by the Society for Maternal-Fetal Medicine
American Journal of Obstetrics and Gynecology
Rapid detection of paternal origin of trisomy 18 by quantitative fluorescent polymerase chain reaction analysis in a fetus associated with increased nuchal translucency thickness and in a pregnancy without an advanced maternal age
Taiwanese Journal of Obstetrics and Gynecology
Chen - 2024 - Rapid detection of paternal origin of trisomy 18 b.pdf
Increased nuchal translucency and associated chromosomal aberrations detected by array comparative genomic hybridisation (acgh) among patients referred to national polish prenatal screening program: A multicenter cohort study - ScienceDirect
Increased nuchal translucency and associated chrom.pdf
L’apport de l’ACPA dans la prise en charge des hyperclartés nucales
Gynécologie Obstétrique Fertilité & Sénologie - Vol. 48 - N° 2 - p. 174-180
Fetal heart defects: potential and pitfalls of first-trimester detection
Congenital heart defects (CHDs) are the leading cause of infant mortality due to birth defects. In the last 15 years, with the shift in screening for aneuploidies to the first trimester, extensive research has concentrated on early screening and detection of CHDs. Early detailed assessment of the fetal heart requires a high level of expertise in early anomaly scanning and fetal echocardiography. However, the detection of major CHDs at 11-13 weeks is influenced by their association with easily detectable markers, such as the nuchal translucency, ductus venosus blood flow and tricuspid regurgitation, and a policy decision as to the objectives of this scan and the allocation of resources necessary to achieve them. The use of transvaginal ultrasound and newer techniques are likely to improve the detection rate. However, the limitations of fetal echocardiography in the first trimester must be borne in mind, and follow-up at mid-gestational echocardiography is prudent in some cases.
Khalil et Nicolaides - 2013 - Fetal heart defects potential and pitfalls of fir.pdf
Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11-13 weeks
OBJECTIVE: To examine the performance of the 11-13 weeks scan in detecting non-chromosomal abnormalities. METHODS: Prospective first-trimester screening study for aneuploidies, including basic examination of the fetal anatomy, in 45 191 pregnancies. Findings were compared to those at 20-23 weeks and postnatal examination. RESULTS: Aneuploidies (n = 332) were excluded from the analysis. Fetal abnormalities were observed in 488 (1.1%) of the remaining 44 859 cases; 213 (43.6%) of these were detected at 11-13 weeks. The early scan detected all cases of acrania, alobar holoprosencephaly, exomphalos, gastroschisis, megacystis and body stalk anomaly, 77% of absent hand or foot, 50% of diaphragmatic hernia, 50% of lethal skeletal dysplasias, 60% of polydactyly, 34% of major cardiac defects, 5% of facial clefts and 14% of open spina bifida, but none of agenesis of the corpus callosum, cerebellar or vermian hypoplasia, echogenic lung lesions, bowel obstruction, most renal defects or talipes. Nuchal translucency (NT) was above the 95th percentile in 34% of fetuses with major cardiac defects. CONCLUSION: At 11-13 weeks some abnormalities are always detectable, some can never be and others are potentially detectable depending on their association with increased NT, the phenotypic expression of the abnormality with gestation and the objectives set for such a scan.
Syngelaki et al. - 2011 - Challenges in the diagnosis of fetal non-chromosom.pdf
Improved detection rate of structural abnormalities in the first trimester using an extended examination protocol
OBJECTIVE: To assess the potential of first-trimester sonography in the detection of fetal abnormalities using an extended protocol that is achievable with reasonable resources of time, personnel and ultrasound equipment. METHODS: This was a prospective two-center 2-year study of 5472 consecutive unselected pregnant women examined at 12 to 13 + 6 gestational weeks. Women were examined using an extended morphogenetic ultrasound protocol that, in addition to the basic evaluation, involved a color Doppler cardiac sweep and identification of early contingent markers for major abnormalities. RESULTS: The prevalence of lethal and severe malformations was 1.39%. The first-trimester scan identified 40.6% of the cases detected overall and 76.3% of major structural defects. The first-trimester detection rate (DR) for major congenital heart disease (either isolated or associated with extracardiac abnormalities) was 90% and that for major central nervous system anomalies was 69.5%. In fetuses with increased nuchal translucency (NT), the first-trimester DR for major anomalies was 96%, and in fetuses with normal NT it was 66.7%. Most (67.1%) cases with major abnormalities presented with normal NT. CONCLUSIONS: A detailed first-trimester anomaly scan using an extended protocol is an efficient screening method to detect major fetal structural abnormalities in low-risk pregnancies. It is feasible at 12 to 13 + 6 weeks with ultrasound equipment and personnel already used for routine first-trimester screening. Rate of detection of severe malformations is greater in early- than in mid-pregnancy and on postnatal evaluation. Early heart investigation could be improved by an extended protocol involving use of color Doppler.
Iliescu et al. - 2013 - Improved detection rate of structural abnormalitie.pdf
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Absent nasal bone at 11–14 weeks of gestation and chromosomal defects
Objective To examine the association between absence of the nasal bone at the 11–14-week ultrasound scan and chromosomal defects. Methods Ultrasound examination was carried out in 3829 fetuses at 11–14 weeks' gestation immediately before fetal karyotyping. At the scan the fetal crown–rump length (CRL) and nuchal translucency (NT) thickness were measured and the fetal profile was examined for the presence or absence of the nasal bone. Maternal characteristics including ethnic origin were also recorded. Results The fetal profile was successfully examined in 3788 (98.9%) cases. In 3358/3788 cases the fetal karyotype was normal and in 430 it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related firstly to the ethnic origin of the mother (2.8% for Caucasians, 10.4% for Afro-Caribbeans and 6.8% for Asians), secondly to fetal CRL (4.6% for CRL of 45–54 mm, 3.9% for CRL of 55–64 mm, 1.5% for CRL of 65–74 mm and 1.0% for CRL of 75–84 mm) and thirdly, to NT thickness, (1.8% for NT < 2.5 mm, 3.4% for NT 2.5–3.4 mm, 5.0% for NT 3.5–4.4 mm and 11.8% for NT ≥ 4.5 mm. In the chromosomally abnormal group the nasal bone was absent in 161/242 (66.9%) with trisomy 21, in 48/84 (57.1%) with trisomy 18, in 7/22 (31.8%) with trisomy 13, in 3/34 (8.8%) with Turner syndrome and in 4/48 (8.3%) with other defects. Conclusion At the 11–14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT thickness and ethnic origin. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
Hyperclarté nucale et hygroma cervical au premier trimestre de la grossesse : diagnostic prénatal et devenir néonatal
Résumé Objectif. – Analyser de façon prospective le devenir des fœtus porteurs d'une hyperclarté nucale (HN) supérieure au 95e percentile pour le terme ou d'un hygroma cervical (HC) entre 10 et 14 SA. Patientes et méthodes. – Les données maternelles (âge, antécédents), fœtales (mesure de la nuque, caryotype, issue de grossesse) et le devenir pédiatrique concernant 223 grossesses uniques avec anomalies de la nuque au premier trimestre (183 fœtus porteurs d'une HN et 40 fœtus porteurs d'un HC) ont été analysées entre 1999 et 2003. Résultats. – La taille moyenne de la nuque était significativement différente entre les deux groupes : 7,4±2,9 mm [3,8–16,9] dans le groupe HC contre 3,7±0,8 mm [3,0–9,0] dans le groupe HN (p<0,05). Le taux d'aneuploïdies était de 55 % (22/40) dans le groupe HC avec 40,9 % (9/22) de monosomies X contre 14,2 % (26/183) d'aneuploïdies dans le groupe HN avec 57,7 % (15/26) de trisomies 21 (p<0,05). Le taux d'issues défavorables (FCS, MFIU, IMG, ENV porteurs de malformations) était de 80 % (32/40) dans le groupe HC contre 18 % (33/183) dans le groupe HN (p<0,05). Parmi les fœtus à caryotype normal, 44,4 % (8/18) des fœtus étaient vivants sans malformations dans le groupe HC contre 93 % (146/157) dans le groupe HN (p<0,05). Discussion et conclusion. – Ces résultats montrent que le diagnostic échographique du type d'anomalie de la nuque au premier trimestre est primordial car les issues de grossesses diffèrent entre HC et HN, même à caryotype normal, avec un taux de malformations associé très différent. Objective. – A prospective study of pregnancy outcome in fetuses with increased nuchal translucency above the 95th centile (group NT) or cystic hygroma (group CH) at 10 to 14 weeks of gestation was performed. Patients and methods. – Maternal and fetal data (nuchal translucency, caryotype, pregnancy outcome) and infant follow-up of 223 fetuses with first trimester nuchal translucency thickness (183 NT and 40 CH) were analysed. Results. – The measurement of nuchal translucency thickness shows a significant difference between group CH and NT (7.4±2.9 mm compared 3.7±0.8 mm). Chromosomal abnormalities were present in 55% (22/40) in group CH, with 9 cases/22 (40.9%) of Turner syndrome, compared with 14.2% (26/183) in group NT with trisomy 21 in 15 cases/26 (57.7%) (P<0.05). The rate of unfavourable outcome of pregnancy (spontaneous abortion, elective termination of pregnancy, serious structural anomalies) was 80% (32/40) in group CH compared with 18% (33/183) in group NT (P<0.05). In chromosomally normal pregnancies, the rate of fetus with no visible serious structural anomalies was 44.4% (8/18) in group CH compared with 93% (146/157) in group NT (P<0.05). Discussion and conclusion. – Our data show ultrasonographic evaluation of the fetal nuchal translucency thickness at the first trimester is actually indispensable. Neonatal outcome and malformation rate in fetuses with increased nuchal translucency or cystic hygroma are different, even with normal karyotype.
Hyperclarté nucale et hygroma cervical au premier trimestre de la grossesse
Ducarme et al. - 2005 - Hyperclarté nucale et hygroma cervical au premier .pdf
Whole exome sequencing in fetuses with isolated increased nuchal translucency: a systematic review and meta-analysis
OBJECTIVE: To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype and chromosomal microarray (CMA) analyses in fetuses with isolated increased nuchal translucency (NT) and normal fetal anatomy at the time of 11-14 weeks scan. MATERIALS AND METHODS: Medline and Embase databases were searched. Inclusion criteria were fetuses with NT >95th percentile, normal karyotype and CMA and no associated structural anomalies at the time of the 11-14 weeks scan. The primary outcome was to estimate the incremental yield of detecting pathogenic or likely pathogenic genetic variants by WES over standard karyotype and CMA analyses in fetuses with isolated increased nuchal translucency. The secondary outcomes were the detection of a genetic variant of unknown significance. Sub-analysis according to different NT cutoffs (between 3.0 and 5.5 mm and > 5.5 mm) and considering fetuses with isolated NT in which fetal anatomy was confirmed to be normal at the anomaly scan were also performed. Random effects model meta-analyses of proportion were used to analyze the data. RESULTS: Eight articles (324 fetuses) were included in the systematic review. Of the fetuses with negative standard karyotype and CMA analysis, the 8.07% (95% CI 5.4-11.3) had pathogenic or likely pathogenic genetic variants detected exclusively by WES. When stratifying the analysis according to NT cutoffs, genetic anomalies detected exclusively at WES analysis were found in 44.70% (95% CI 26.8-63.4) of fetuses with NT between 3.0 mm and 5.5 mm and 55.3% (95% CI 36.6-73.2) in those fetuses with NT >5.5 mm and positive WES results. The 7.84% (95% CI 1.6-18.2) had variants of unknown significance identified by WES. When considering fetuses with isolated increased NT and normal fetal anatomy at the anomaly scan, the rate of pathogenic or likely pathogenic genetic variants detected by WES was 3.87% (95% CI 1.6-7.1), while variants of unknown significance were detected in 4.27% (95% CI 2.2-7.0) of cases. CONCLUSIONS: Pathogenic and likely pathogenic genetic variants detected by WES are present in a significant proportion of fetuses with increased NT but normal standard karyotype and CMA analysis, also when no anomalies are detected at the anomaly scan. Further large studies sharing objective protocols of imaging assessment are needed to confirm these findings and to elucidate which gene panels should be assessed in fetuses with isolated increased NT to rule out associated genetic anomalies, which may potentially impact post-natal outcomes.
Whole exome sequencing in fetuses with isolated increased nuchal translucency
Prenatal diagnosis and early childhood outcome of fetuses with extremely large nuchal translucency
OBJECTIVE: To evaluate the prenatal and perinatal outcome of fetuses with extremely large nuchal translucency (eNT) thickness (≥ 6.5 mm). METHODS: 193 (0.61%) singleton fetuses with eNT were retrospectively included. Anomaly scan, echocardiography, and chromosomal and genetic test were included in our antenatal investigation. Postnatal follow-up was offered to all newborns. RESULTS: Major congenital anomalies included congenital heart defect (32.6%, 63/193), hydrops fetalis (13.5%, 26/193), omphalocele (9.3%, 18/193), and skeletal dysplasia (7.8%, 15/193) et al. Abnormal karyotype was identified in 81/115 (70.4%) cases including Turner syndrome (n = 47), Trisomy 18 (n = 17), Trisomy 21 (n = 9), and Trisomy 13 (n = 3). Chromosomal microarray analysis provided informative results with 3.6% (1/28) incremental diagnostic yield over conventional karyotyping. The diagnostic yield of exome sequencing is 10.0% (2/20). There was no significant increase [Odds Ratio (OR) = 1.974; 95% confidence interval 0.863-4.516; P = 0.104] in the incidence of chromosomal defects despite the presence of other structural anomalies. Only 13 fetuses were successfully followed up and survived at term, no one was found with developmental delay or mental retardation. CONCLUSIONS: Extremely large NT has a high risk of chromosomal abnormality. CMA and ES improve chromosomal genomic and genetic diagnosis of fetal increased NT. When cytogenetic analysis and morphology assessment are both normal, the outcome is good.
Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study
OBJECTIVES: To examine the utility of measuring fetal nuchal translucency thickness in screening for major defects of the heart and great arteries at 10-14 weeks of gestation. DESIGN: Population based cohort study. SUBJECTS: 29 154 singleton pregnancies with chromosomally normal fetuses at 10-14 weeks of gestation. SETTING: Fetal medicine centre in London. MAIN OUTCOME MEASURE: Prevalence of major defects of the heart and great arteries. RESULTS: Of 50 cases with major defects of the heart and great arteries (prevalence 1.7 per 1000 pregnancies) 28 (56%, 95% confidence interval 42% to 70%) were in the subgroup of 1822 pregnancies with fetal nuchal translucency thicknesses above the 95th centile of the normal range. The positive and negative predictive values for this cut off point of nuchal translucency thickness were 1.5% and 99.9% respectively. CONCLUSIONS: Measurement of fetal nuchal translucency thickness-traditionally used to identify fetuses at high risk of aneuploidy-at 10-14 weeks of gestation can identify a large proportion of fetuses with major defects of the heart and great arteries.
Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation
Nuchal Translucency and Congenital Heart Defects
Nuchal translucency comprises a temporary accumulation of fluid in the subcutaneous tissue on the back of a fetus’s neck, which accompanies the crown-rump length and is observed through an ultrasound performed between 11 and 13 weeks + 6 days gestation. Nuchal translucency is considered to be above normal when values are higher than the 95th/99th percentile or equal to or higher than 2.5/3.5 mm. The first connection between increased nuchal translucency and the presence of congenital heart defects is described in the study of Hyett et al., who observed that they are directly proportional. Since that time, several studies have been conducted to understand if nuchal translucency measurements can be used for congenital heart defect screening in euploid fetuses. However, there is great variability in the estimated nuchal translucency cutoff values for congenital heart defect detection. The purpose of this review was to understand how increased nuchal translucency values and congenital heart defects are related and to identify which of these defects are more frequently associated with an increase in these values.
Nuchal translucency and its relationship to congenital heart disease
Nuchal translucency refers to the normal subcutaneous space, observed on first trimester ultrasound evaluation, between the skin and cervical spine. Increased nuchal translucency is known to be associated with an increased risk of aneuploidy, particularly Trisomy 21, and recent studies have also identified increased nuchal translucency as a nonspecific marker for various genetic syndromes and multiple structural anomalies, to include congenital heart disease. This increased risk applies to euploid and aneuploid pregnancies and is directly related to the degree of nuchal translucency thickening. This article reviews the role of nuchal translucency as a screening tool for congenital heart disease
Prenatal Diagnosis of Congenital Heart Disease
Increased nuchal translucency and congenital heart disease
Sonographic assessment of fetal nuchal translucency (NT) thickness is the cornerstone of screening for chromosomal abnormality at 11-13(+6) weeks gestation. This marker was first recognized in pregnancies being karyotyped for advanced maternal age, but its underlying pathophysiology remains to be fully determined. Although increased NT is clearly associated with changes in both lymphatic and cardiac development, neither is an obvious causative agent. The association with cardiac defects has now being subjected to a significant amount of research, with a large body of evidence showing that this marker is also a screening tool for major cardiac defects - although it performs more modestly than for chromosomal abnormality. The field continues to change rapidly. Recent evidence that uses a combination of increased NT, tricuspid regurgitation and abnormal flow in the 'a' wave of the ductus venosus can provide an effective screening strategy to predict many major cardiac defects at this early stage of pregnancy.
Sonographic assessment of fetal nuchal translucency (NT) thickness is the cornerstone of screening for chromosomal abnormality at 11–13+6weeks gestation. This marker was first recognized in pregnancies being karyotyped for advanced maternal age, but its underlying pathophysiology remains to be fully determined. Although increased NT is clearly associated with changes in both lymphatic and cardiac development, neither is an obvious causative agent. The association with cardiac defects has now being subjected to a significant amount of research, with a large body of evidence showing that this marker is also a screening tool for major cardiac defects — although it performs more modestly than for chromosomal abnormality. The field continues to change rapidly. Recent evidence that uses a combination of increased NT, tricuspid regurgitation and abnormal flow in the ‘a’ wave of the ductus venosus can provide an effective screening strategy to predict many major cardiac defects at this early stage of pregnancy.
Increased nuchal translucency with normal karyotype and anomaly scan: What next?
Over the years, it has become clear that increased nuchal translucency is a marker for chromosomal abnormalities, and it is also associated with a wide spectrum of structural anomalies, genetic syndromes, a higher risk of miscarriage, and intrauterine fetal death. These risks are all proportionally related to the degree of nuchal translucency enlargement. After the initial assessment of increased nuchal translucency, parents should be counselled by the fetal medicine specialist about the possible outcomes and the value of additional karyotyping and array comparative genomic hybridisation. A detailed late first-trimester and subsequent 20-week scan should aim at identifying structural anomalies, with special focus on the fetal heart and subtle dysmorphic features. In the absence of structural anomalies or markers, the chance of a favourable outcome is high.
Increased nuchal translucency with normal karyotype and anomaly scan
Best Practice & Research Clinical Obstetrics & Gynaecology
Cystic hygroma: Comparison between prenatal and postnatal diagnosis
Antenatal diagnosis of congenital malformation often leads to opportunities for intervention in the pregnancy that may have a profound effect on the outcome of the fetus. The accuracy of the diagnostic technique is a critical factor in judging the appropriateness of such interventions. This article reports the current accuracy of prenatal ultrasound diagnosis of cystic hygroma (CH) in a region with a population of 3.5 million and an annual birth rate of 52,000. During a 32-month period (to December 1994), 113 diagnoses of CH were reported to the South East Thames Regional Congenital Malformation Registry. Eighty-nine diagnoses were made prenatally and 24 were made postnatally (at delivery or postmortem). The number of confirmed cases of CH was 52 (46% total diagnoses). The prenatal diagnoses were established at a mean gestational age of 19 weeks. Fifty-six (63%) pregnancies with a prenatal diagnosis of fetal CH were terminated; in only 25% of these was the presence of CH confirmed after termination. Overall, of the 89 prenatal diagnoses, 28 (32%) were confirmed, 45 (50%) were incorrect, and 16 (18%) could not be confirmed or refuted. Only 24% of fetuses with a prenatal diagnosis of CH were live born. The survival rate at 1 year for the live-born infants with CH in this series was 88%. The diagnosis of fetal CH has a recognised association with chromosomal abnormalities, and consequently may lead to termination of the pregnancy. A potential error rate of almost 70% in the prenatal ultrasound diagnosis of this condition requires clinicians to adopt a more cautious approach to the management of the fetus with “cystic hygroma.”
Papers Presented at the 42nd Annual International Congress
Résumé Objectifs Hyperclarté nucale et hygroma colli ont un pronostic néonatal, lorsque le caryotype est normal, qui dépend de ce qui sera découvert lors du suivi médical. L’ACPA a été systématiquement incorporé à ce suivi par les équipes de diagnostic anténatal. Il n’existe pas de recommandation et peu de données dans la littérature sur les avantages à réaliser cet examen de façon systématique. L’objectif de notre étude est d’évaluer l’apport de l’ACPA dans ce suivi. Méthodes Cinquante et une patientes ont été incluses sur 18 mois et suivies jusqu’au dénouement de leur grossesse aux centres de diagnostic anténatal de Brest et d’Amiens. Le critère d’inclusion était une hyperclarté nucale>3,5mm en échographie du 1er trimestre. Des analyses d’ADN fœtal, par ChromoQuant et ACPA effectuées sur ponction de villosité choriale, et une échographie à 18 SA étaient réalisées durant ce suivi. Résultats L’ACPA n’a été déterminante qu’à 2 reprises. L’échographie à 18 SA semble plus sensible dans le dépistage d’une anomalie. Lorsque l’ACPA révélait une anomalie, l’échographie permettait d’envisager la présence d’une malformation. Dans 10 cas, l’ACPA n’a pu être interprétée sur la ponction de villosité choriale. Dans 9 cas, une amniocentèse a été réalisée afin d’obtenir ce résultat. Conclusion Au vu des résultats de cette étude l’ACPA est peu souvent déterminante ou décisive dans la réalisation d’une IMG. Ces éléments nous amènent à réfléchir à la nécessité de maintenir cet examen avant 14SA ou bien de le proposer en seconde intention après apparition de signes échographiques à 18 SA. Objectives Increased nuchal translucency and cystic hygroma have a neonatal prognosis, when the karyotype is normal, which depends on the findings during the medical follow-up. Array comparative genomic hybridization (aCGH) has been systematically included in this follow-up by prenatal diagnosis teams. There are no guidelines and little information on the advantages of carrying out this test systematically. The aim of our study is to evaluate the contribution of the aCGH in the medical follow-up. Methods Fifty-one patients were included during 18 months and followed till the end of their pregnancy in prenatal diagnosis centers in Brest and Amiens. Inclusion criterion was a nuchal translucency above 3,5mm on the first trimester ultrasound. A fetal DNA ChromoQuant and aCGH analysis on chorionic villi sampling, and an ultrasound at 18 weeks of gestation were performed during the follow-up. Results The aCGH was decisive in only 2 cases. The ultrasound at 18 weeks gestation seemed to be more sensible in the detection of an abnormality. When the aCGH relieved an abnormality, the ultrasound permitted already to detect the presence of a deformity. In 10 cases, the aCGH could not be interpreted on the chorionic villi sampling. In 9 cases, an amniocentesis was performed in order to obtain this result. Conclusion Given the results of this study, the aCGH was rarely determinant or decisive on the realization of a therapeutic abortion. These elements make us reflect on the necessity of maintaining this test before 14 weeks of gestation or propose it as a second-line test after the ultrasound shows signs at 18weeks of gestation.
Apport de l’ACPA dans le diagnostic étiologique des fœtus avec hyperclarté nucale au premier trimestre de grossesse : étude rétrospective multicentrique nationale incluant 720 fœtus
À l’échographie du premier trimestre, l’hyperclarté nucale est définie par une mesure rapportée à la longueur crânio-caudale fœtale supérieure à 3,5mm. Des études ont montré que l’augmentation de l’épaisseur de la clarté nucale était associée à un risque d’anomalies chromosomiques. Une récente méta-analyse [1] a montré qu’environ 4 % de CNVs pathogènes cryptiques étaient identifiés chez ces fœtus. Cependant, les séries de fœtus analysés comprennent le plus souvent un faible nombre de cas. L’objectif de notre étude consiste à déterminer la fréquence et la nature des CNVs identifiés par ACPA sur une large cohorte de fœtus présentant une hyperclarté nucale isolée≥3,5mm. Il s’agit d’une étude rétrospective, multicentrique nationale, incluant 720 fœtus. Chez 121 fœtus (16,8 %), une aneuploïdie a été détectée par une technique rapide. Chez les 599 fœtus euploïdies restants, 53 CNVs (8,8 %) ont été identifiés par ACPA : 17 (2,8 %) ont été considérés comme pathogènes, dont 12 (2 %) cryptiques. Par ailleurs, 8 VOUS (1,3 %) et 7 (1,2 %) CNVs à pénétrance incomplète et/ou expressivité variable, non visibles sur le caryotype, ont été mis en évidence. Enfin, 1 (0,2 %) CNV a été considéré de découverte fortuite sans lien avec le phénotype. Notre étude confirme l’intérêt de l’ACPA dans le bilan étiologique des fœtus avec une hyperclarté nucale isolée. Cependant, le taux de CNVs pathogènes détectés est inférieur à celui rapporté dans la littérature. Ceci est principalement lié à la classification du CNV identifié et à l’inclusion dans notre étude de fœtus présentant une hyperclarté nucale isolée. De façon intéressante, 5 (0,8 %) CNVs situés en 1q21,1 et 15q11.2 connus pour être associés à une malformation cardiaque ont été mis en évidence. La fréquence de ces CNVs dans notre étude révèle leur rôle dans la survenue de l’hyperclarté nucale mais ils soulèvent des problèmes de conseil génétique.
Apport de l’ACPA dans le diagnostic étiologique des fœtus avec hyperclarté nucale au premier trimestre de grossesse
99E CONGRÈS DE L'ASSOCIATION DES MORPHOLOGISTES 22ES JOURNÉES DU COLLÈGE DES HISTOLOGISTES, EMBRYOLOGISTES ET CYTOGÉNÉTICIENS, REIMS 09-11 MARS 2017