How does cell-based non-invasive prenatal test (NIPT) perform against chorionic villus sampling and cell-free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark

Objectives

We 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 Methods

Study 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.

Results

Study 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.

Conclusion

Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome.     

Fetal brain imaging in isolated congenital heart defects – a systematic review and meta-analysis

Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990–2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI −6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of −0.51 (95%CI −0.84; −0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score −0.70 95%CI −0.99; −0.41) in left-sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. © 2016 John Wiley & Sons, Ltd.     

Non-invasive prenatal testing (NIPT): Combination of copy number variant and gene analyses using an “in-house” target enrichment next generation sequencing—Solution for non-centralized NIPT laboratory?

Objective

Recent studies have integrated copy number variant (CNV) and gene analysis using target enrichment. Here, we transferred this concept to our routine genetics laboratory, which is not linked to centralized non-invasive prenatal testing (NIPT) facilities.

Method

From a cohort of 100 pregnant women, 22 were selected for the analysis of maternal genomic DNA (gDNA) along with fetal cell-free DNA. Using targeted enrichment, 135 genes were analyzed, combined with aberrations of chromosomes 21, 18, 13, X, and Y. The data were subjected to specificity and sensitivity analyses, and correlated with the results from invasive testing methods.

Results

The sensitivity/specificity was determined for the CNV analysis of chromosomes: 21 (80%/75%), 18 (-/82%), 13 (100%/67%), and Y (100%/100%). The gene detection was valid for maternal gDNA. However, for cell-free fetal DNA, it was not possible to determine the boundary between an artifact and a real sequence variant.

Conclusion

The target enrichment method combining CNV and gene detection seems feasible in a regular laboratory. However, this method can only be responsibly optimized with a sufficient number of controls and further validation on a strong bioinformatic background. The present results showed that NIPT should be performed in specialized centers, and that its introduction to isolated laboratories may not provide valid data.     

Informational governance – A systematic literature review of governance for sustainability in the Information Age

The rapid developments in all kinds of new information technologies, information networks and social media are increasingly affecting societies around the world. The so termed Information Age not only influences social relationships, economy and science, but also governance. Against this background and in the specific field of sustainability, informational governance is an emerging concept. It addresses two interrelated processes: (1) new forms of governing through information, and (2) transformative changes in governance institutions due to the new information flows. The aim of this article is to gain more insights into ways in which the Information Age impacts sustainability, and to suggest a research agenda with relevance to the field of informational governance. A systematic literature review resulted in a selection of 39 articles, of which 23 and 16 articles were identified in two-parallel searches. The increased human interconnectedness through e-governance, self-organization, private governing and empowerments are identified as core informational governance trends dealing with sustainability in the Information Age, and essential to future research.     

Is there a role for fetal interventions in gastroschisis management? – An updated comprehensive review

We conducted a comprehensive evidence-based review on the epidemiology and current standard of care of gastroschisis management as well as the pathophysiology, rationale and feasibility of fetal therapy as a viable alternative. Gastroschisis is a periumbilical abdominal wall defect characterized by abdominal viscera herniation in utero. It affects 4 in 10 000 live births, but the prevalence has steadily increased in recent years. Gastroschisis is typically diagnosed on routine second-trimester ultrasound. The overall prognosis is favorable, but complex gastroschisis, which accounts for about 10% to 15% of cases, is associated with a higher mortality, significant disease burden and higher healthcare costs due to long- and short-term complications. The current standard of care has yet to be established but generally involves continued fetal surveillance and multidisciplinary perinatal care. Postnatal surgical repair is achieved with primary closure, staged silo closure or sutureless repair. Experimental animal studies have demonstrated the feasibility of in utero closure, antiinflammatory therapy and prenatal regenerative therapy. However, reports of early preterm delivery and amnioinfusion trials have failed to show any benefit in humans. Further experimental studies and human trials are necessary to demonstrate the potential benefit of fetal therapy in gastroschisis.