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Objectives: Congenital heart defect (CHD) is the one of the major causes for neonatal lethality. And ultrasound screening enables the early diagnosis of CHD in prenatal stage. Emerging studies by using chromosomal microarray analysis of prenatal samples show that pathogenic copy number variants (CNVs) are highly associated with CHD. Methods: Here, we collected DNA samples from 145 unrelated fetuses with CHD diagnosed by ultrasound screening and subjected them for CNV analysis by low-pass whole-genome sequencing. CNV classification was performed according to the guideline from the American College of Medical Genetics. Maternal ages are 27.6±3.73, while the gestational weeks are 24.4±5.2. Sixty-one samples out of them are intra-cardiac defects (42.1%) and the remaining samples are extra-cardiac abnormalities (57.9%).Subtype classification of two groups is different, in intracardiac defect, the top were TOF (21.3%), TGA(14.8%) and AVSD (11.8%), while, the other were VSD (21.4%), AVSD (16.7%) and PS (13.1%). Results: Aneuploidies were identified in 29 (20%) fetuses, 27 out of them were with extra-cardiac abnormalities. Pathogenic CNVs were detected in seven cases, including a heterozygous loss at 22q13 harbouring FBLN1 and a gain at 10q23.31q26.3 with SHOC2 and ANKRD1.There were 344 unknown clinical significance micro-duplication or micro-deletion found in 91 samples, the number of CNV per sample was more in extra-cardiac abnormalities group when compared to intra-cardiac defect (p-value = 0.1514). 7.53% of which were predicted to be pathogenic by DECIPHER and GeneReviews. Conclusions: Our study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in CHD patients. EP06.03Be aware of a diagnostic delay: Rotterdam's experience with NIPT in 1071 high-risk pregnancies Objectives: It is expected that many pregnant women will choose for NIPT instead of first trimester combined testing (ftCT). As a consequence high risk pregnancies may be identified later on in the pregnancy. NIPT performed in high risk pregnancies may lead to a diagnostic delay of some chromosome aberrations. The aim of this study was to evaluate the risk of a diagnostic delay in our cohort of high risk pregnancies tested with NIPT. Methods: 2014-2015 NIPT was performed in 1071 high risk pregnancies (risk > 1:200 after ftCT). 39 (3.6%) women subsequently chose array testing due to further doubts (10), an ultrasound anomaly found later on in the pregnancy (21) or fetal death (IUFD, 8). Results: In 3 fetuses a pathogenic fetal unbalanced chromosome aberration matching the indication was found (isochromosome Xq, a de novo atypical 22q11 microdeletion and triploidy). Thus, in ca. 1:350 (3/1071) ''false'' reassurance was given with normal NIPT results and a diagnostic delay to the second trimester occurred. This is an underestimation of the overall diagnostic delay since not all unbalanced chromosome aberrations manifest ultrasound anomalies or cause IUFD. Besides this, developmental delay and intellectual disability are not im...

BackgroundWhen cell-free DNA (cfDNA) testing is used as a secondary screening tool following combined first-trimester screening (cFTS), cFTS is used to estimate the prior risk for chromosome abnormalities. This study aimed to assess the factors that are associated with common and atypical abnormalities following cFTS, including cFTS risk, advanced maternal age, increased nuchal translucency (NT) ≥3.5 mm, and abnormal levels of serum markers.MethodsWe reviewed a historical cohort of 1855 Chinese women carrying singleton pregnancies with a positive cFTS [at a threshold of 1:250 for trisomy (T) 21 or 1:180 for T18] in one public hospital over a five-year period. All chromosome abnormalities were confirmed by invasive prenatal diagnosis (IPD) with karyotyping, with or without array comparative genomic hybridization. Using multivariable binary logistic regression analysis, we determined the parameters that were associated with common and atypical abnormalities.ResultsOverall, the prevalence of common and atypical abnormalities was 6.2 and 1.2%, respectively, and the prevalence increased with the risk of T21 by cFTS. In pregnancies with a risk of T21 > 1 in 100, a high risk of both T21 and T18, an increased NT, or a pregnancy-associated plasma A (PAPP-A) level <  0.2 multiple of medians (MoM), the prevalence of common abnormalities was 12.2, 64.7, 25.5 and 33.8%, respectively, while that of atypical abnormalities was 1.6, 3.9, 4.2, and 7.4%, respectively. In the multivariable binary logistic regression analysis, out of these four factors, only two (increased NT and PAPP_A <  0.2 MoM) were significant predictors of common and atypical abnormalities, respectively. Of all positive cFTS pregnancies, 50.4% did not have any of these four factors, and the prevalence of common and atypical abnormalities was 1.1 and 0.6%, respectively. There were three atypical abnormalities, all of which were mosaicism, and they were detected among women with IPD alone. The ages of these women were ≥ 35 years. All three pregnancies were continued after proper counseling. After giving birth, only one child had mild abnormalities, while the other two were phenotypically normal.ConclusionsOur study identified factors associated with common and atypical abnormalities after cFTS. These factors can be used to estimate the prior risk for these abnormalities to help with post-cFTS counseling in terms of choosing between cfDNA testing and IPD.

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Necrotizing fasciitis always carries very high mortality and morbidity rates. It can be due to group A beta-haemolytic streptococci, which are traditionally described as the flesh-eating bacteria. More commonly, it is related to a mixed growth of bacteria that can be secondary to trauma or surgery. Secondary necrotizing fasciitis due to concomitant soft tissue infection is uncommon. We reported a fatal case of necrotizing fasciitis which was caused by a coexisting psoas abscess. A search for concomitant soft tissue infection is warranted in patients presenting with necrotizing fasciitis. This article also reviewed the clinical tools that may help to make an early diagnosis of the disease.