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Introduction: The aim of this retrospective cohort study was to determine the potential diagnostic yield of prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results. Material and methods: In the period 2013‐2016, 391 pregnant women with fetal ultrasound anomalies who received normal chromosomal microarray results, were referred for additional genetic counseling and opted for additional molecular testing pre‐ and/or postnatally. Most of the couples received only a targeted molecular test and in 159 cases (40.7%) whole exome sequencing (broad gene panels or open exome) was performed. The results of these molecular tests were evaluated retrospectively, regardless of the time of the genetic diagnosis (prenatal or postnatal). Results: In 76 of 391 fetuses (19.4%, 95% CI 15.8%‐23.6%) molecular testing provided a genetic diagnosis with identification of (likely) pathogenic variants. In the majority of cases (91.1%, 73/76) the (likely) pathogenic variant would be detected by prenatal whole exome sequencing analysis. Conclusions: Our retrospective cohort study shows that prenatal whole exome sequencing, if offered by a clinical geneticist, in addition to chromosomal microarray, would notably increase the diagnostic yield in fetuses with ultrasound anomalies and would allow early diagnosis of a genetic disorder irrespective of the (incomplete) fetal phenotype. [ABSTRACT FROM AUTHOR]

Prenatal diagnostics has been impacted by technological changes in the past decade, which have affected the diagnostic yield. The aim of this study was to evaluate the impact of SNP array and noninvasive prenatal testing (NIPT) on the diagnostic yield and the number of invasive tests in our center. The frequency of pathogenic fetal unbalanced chromosome aberrations was studied in 10,005 cases referred for prenatal testing in 2009-2015. Chromosomal SNP microarray analysis replaced karyotyping in all invasively tested pregnancies and since 2014 a choice between NIPT and diagnostic testing with microarray was offered to women with an increased risk for common aneuploidy. The introduction of microarray led to an additional yield of submicroscopic pathogenic chromosome aberrations: 3.6% in fetuses with ultrasound anomalies and 1.9% in fetuses without ultrasound anomalies. The introduction of NIPT led to a decrease of invasive tests and of diagnostic yield. Moreover, a diagnostic delay in about 1:350 cases was observed. Since 20%-33% of pathogenic fetal chromosome aberrations are different from the common aneuploidies and triploidy, whole-genome analysis should be offered after invasive sampling. Because NIPT (as a second screening) has led to a decreased diagnostic yield, it should be accompanied by an appropriate pretest counseling. [ABSTRACT FROM AUTHOR]

Background & Aims: General practitioners (GPs) in the Netherlands have open access to flexible sigmoidoscopy (FS) for patients with lower gastrointestinal symptoms, but not to colonoscopy. This study was performed to investigate the yield of FS in GP-referred patients, to evaluate the proportion of patients in whom additional colonoscopy was performed and to investigate whether there was a subgroup of patients referred for symptoms with a low risk of detecting significant findings. Methods: All patients undergoing FS in 2008 and 2009 who were referred by GPs were analyzed. Indications for additional colonoscopy were the presence of polyps and/or colorectal cancer (CRC), polyp screening or surveillance, incomplete FS or other reasons. Results: In total, 916 patients underwent FS. A cause for the symptoms was found in 44.2% of patients. In patients aged 50 years or older, additional colonoscopy was more frequently performed than in younger patients (27.5% vs. 9.6%, OR=3.6 [95% CI 2.4-5.4]), mainly due to a higher prevalence of adenomatous polyps (29.9% vs. 10.5%, OR=3.6 [95% CI 2.4-5.4]) and CRC (7.5% vs. 1.3%, OR=6.2 [95% CI 2.2-17.5]) during FS. In 7.8% patients undergoing FS for abdominal pain as the presenting symptom, a probable cause for the symptoms was found, mainly diverticular disease. Conclusion: Due to the high prevalence of polyps and CRC in symptomatic patients aged 50 years or older undergoing FS, an additional colonoscopy is performed frequently. In patients referred with abdominal pain, FS is unlikely to reveal a relevant cause for the symptoms. [ABSTRACT FROM AUTHOR]

Background: Two technological innovations in the last decade significantly influenced the diagnostic yield of prenatal cytogenetic testing: genomic microarray allowing high resolution analysis and noninvasive prenatal testing (NIPT) focusing on aneuploidy. To anticipate future trends in prenatal screening and diagnosis, we evaluated the number of invasive tests in our center and the number of aberrant cases diagnosed in the last decade. Methods: We retrospectively analyzed fetal chromosomal aberrations diagnosed in 2009–2018 in 8,608 pregnancies without ultrasound anomalies. Results: The introduction of NIPT as the first‐tier test led to a substantial decrease in the number of invasive tests and a substantially increased diagnostic yield of aneuploidies in the first trimester. However, we have also noted a decreased detection of submicroscopic aberrations, since the number of invasive tests substantially decreased. We have observed that pregnant women were interested in broader scope of prenatal screening and diagnosis than detection of common trisomies. Conclusion: Since the frequency of syndromic disorders caused by microdeletions/microduplications is substantial and current routine NIPT and ultrasound investigations are not able to detect them, we suggest that a noninvasive test with resolution comparable to microarrays should be developed, which will also meet patient's needs. [ABSTRACT FROM AUTHOR]