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ObjectivesWe aimed to compare cell-based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell-free NIPT (cfNIPT).Material and MethodsStudy 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA.ResultsStudy 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT.ConclusionCirculating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome.

To perform a morphological evaluation of the ductus venosus, heart and jugular lymphatic sac (JLS) in first-trimester human fetuses with normal and abnormal ductus venosus flow velocity waveforms (DV-FVWs) and normal and increased nuchal translucency (NT). Postmortem examination was performed on fetuses with increased NT or structural malformations with previous NT and DV-FVW measurements. Ductus venosus morphology was examined using markers for endothelium, smooth muscle actin (SMA), nerves and elastic fibers. Fetal hearts were studied by microscopy. The nuchal region was analyzed using markers for lymphatic vessels, endothelium, SMA and nerves. Two trisomy 21 and two trisomy 18 fetuses with increased NT and abnormal DV-FVWs were analyzed. As a control, one euploid anencephalic fetus with normal NT, cardiac anatomy and DV-FVWs was examined. Similar endothelial and SMA expression was observed in the ductus venosus in all fetuses. Nerve and elastic fiber expression were not detected. Three trisomic fetuses showed cardiac defects, one trisomic fetus demonstrated normal cardiac anatomy. The JLS was abnormally enlarged or contained red blood cells in all trisomic fetuses. The control fetus showed a normal JLS. Abnormal DV-FVWs are not justified by alterations in ductus venosus morphology. DV-FVWs most probably reflect intracardiac pressure. © 2016 John Wiley & Sons, Ltd

Objective: To perform a morphological evaluation of the ductus venosus, heart and jugular lymphatic sac (JLS) in first-trimester human fetuses with normal and abnormal ductus venosus flow velocity waveforms (DV-FVWs) and normal and increased nuchal translucency (NT). Method: Postmortem examination was performed on fetuses with increased NT or structural malformations with previous NT and DV-FVW measurements. Ductus venosus morphology was examined using markers for endothelium, smooth muscle actin (SMA), nerves and elastic fibers. Fetal hearts were studied by microscopy. The nuchal region was analyzed using markers for lymphatic vessels, endothelium, SMA and nerves. Results: Two trisomy 21 and two trisomy 18 fetuses with increased NT and abnormal DV-FVWs were analyzed. As a control, one euploid anencephalic fetus with normal NT, cardiac anatomy and DV-FVWs was examined. Similar endothelial and SMA expression was observed in the ductus venosus in all fetuses. Nerve and elastic fiber expression were not detected. Three trisomic fetuses showed cardiac defects, one trisomic fetus demonstrated normal cardiac anatomy. The JLS was abnormally enlarged or contained red blood cells in all trisomic fetuses. The control fetus showed a normal JLS. Conclusion: Abnormal DV-FVWs are not justified by alterations in ductus venosus morphology. DV-FVWs most probably reflect intracardiac pressure. What's Already Known About This Topic? Ultrasound examination of ductus venosus flow velocity waveforms is used to indirectly assess fetal cardiac function and the fetal hemodynamic condition. Abnormal first-trimester ductus venosus flow velocity waveforms are related to chromosomal abnormalities, cardiac defects and increased nuchal translucency. Abnormal formation of the jugular lymphatic sacs is involved in the development of increased nuchal translucency. What Does This Study Add? Abnormal ductus venosus flow velocity waveforms are not caused by local alterations in ductus venosus morphology but reflect a changed hemodynamic status. The morphology of the ductus venosus is not related to abnormal ductus venosus flow velocity waveforms, chromosomal abnormalities, cardiac anatomy and increased nuchal translucency. Increased nuchal translucency in first-trimester human fetuses coincides with abnormal jugular lymphatic sac development.

A dysmorphic boy with severe mental retardation was found on array CGH to have an insertional translocation of chromosome 16p13.3 into the short arm of chromosome 22, karyotype 46,XY,.ish der(22),ins(22;16)(p13;p13.3p13.3) de novo. His clinical features overlap with the reported cases of 'duplication 16p' syndrome, namely a round face, hypertelorism, a long philtrum, micrognathia, a thin upper lip, a posterior cleft palate and low set, simple ears, clubbed feet, severe developmental delay, psychomotor retardation and seizures. This 4-year boy with trisomy 16p13.3 has the smallest duplication reported of this critical region, which could not be detected without array CGH. The maximal duplicated region is gene rich and contains about 80 genes and/or candidate genes. Assignment of the genes that contribute to the observed phenotype awaits the characterisation of other patients with small duplications in this region.

Trisomy 18, or Edwards syndrome, is the second most common chromosome anomaly after trisomy 21. Various types of congenital heart diseases are seen in the majority of trisomy 18 patients. Palliative treatment of right ventricular outflow tract (RVOT) stenosis includes options like balloon dilatation, stenting and surgery. Herein, we present a case with trisomy 18 and double outlet right ventricle, pulmonary stenosis, and ventricular septal defect. During the follow-up, at the age of three months, his saturation dropped to 70% and an interventional procedure was planned. The patient was considered high risk, and after discussing treatment options with the family, RVOT stenting was chosen. The patient was lost on the 8th day of the follow-up.

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35 þ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7–22.4) for trisomy 21, 5.0 (95% CI 4.8–5.1) for trisomy 18 and 2.0 (95% CI 1.9–2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9–11.5) for trisomy 21, 1.04 (95% CI 0.96–1.12) for trisomy 18 and 0.48 (95% CI 0.43–0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence., peer-reviewed