Prenatally detected copy number variants in a national cohort: A postnatal follow‐up study

Abstract

Objective Belgian genetic centers established a database containing data on all chromosomal microarrays performed in a prenatal context. A study was initiated to evaluate postnatal development in children diagnosed prenatally with a non‐benign copy number variant (CNV). Methods All children diagnosed with a prenatally detected non‐benign CNV in a Belgian genetic center between May 2013 and February 2015 were included in the patient population. The control population consisted of children who had undergone an invasive procedure during pregnancy, with no or only benign CNVs. Child development was evaluated at 36 months using three (3) questionnaires: Ages and Stages Questionnaire Third edition, Ages and Stages Questionnaire Social‐Emotional Second Edition and a general questionnaire. Results A significant difference in communication and personal‐social development was detected between children with a reported susceptibility CNV and both children with an unreported susceptibility CNV and the control population. The outcome of children with a particular CNV is discussed in a case‐by‐case manner. Conclusion Our postnatal follow‐up project of children with a prenatally detected non‐benign CNV is the first nationwide project of its kind. A higher number of cases for each CNV category is however needed to confirm our findings.

Perinatal outcomes and genomic characteristics of fetal copy number variants: An individual record linkage study of 713 pregnancies

“…The prevalence of pCNVs in our cohort was 3.3%, which was similar to that reported in a published review of 23,865 pCNVs 29 . Our study of 230 pCNVs is the largest to include birth outcomes, with previous publications containing smaller cohorts (range 5–93) and/or only reporting perinatal outcomes for a small subset 10–14,18 . Our summary statistics on preterm birth and low birth weight provide general prognostic information that can be used for counseling couples about obstetric outcomes for pCNVs, particularly for rare pCNVs where data on obstetric outcomes are lacking and planning ongoing management in a high risk model of prenatal care.…”

“…There is a dearth of current literature on perinatal outcomes of fetal pCNVs and VUS, in terms of the number of live births and perinatal deaths. Published studies are limited by small sample sizes, selection bias due to limited indications for prenatal diagnosis, and incomplete reporting of perinatal outcomes 10–19 . Perinatal outcomes are likely influenced by indication for prenatal diagnosis, such as an ultrasound abnormality, as well as genomic location and CNV size.…”

“…Published studies are limited by small sample sizes, selection bias due to limited indications for prenatal diagnosis, and incomplete reporting of perinatal outcomes. [10][11][12][13][14][15][16][17][18][19] Perinatal outcomes are likely influenced by indication for prenatal diagnosis, such as an ultrasound abnormality, as well as genomic location and CNV size.…”

Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross‐sectional study with healthcare professionals

“…A further consideration is how we define and categorise VUS. For example, 22q11 duplication may be called a VUS in some countries, 9 and a pathogenic variant of low penetrance or a susceptibility loci in others 2,39 . The guidelines are also nondirective on this matter; for example, for 22q11 duplication the UK Royal College of Pathologists says ‘Consider detailed scan looking for associated anomalies or reporting in a clinical context’ 26 .…”

Perinatal outcomes after a prenatal diagnosis of a fetal copy number variant: A retrospective population-based cohort study

“…It is unknown what factors contributed to the higher recruitment rate but one factor could be the clinician-patient relationship as the treating doctor facilitated the contact between the participant and the research team, rather than a hospital departmental representative as in our study. Moreover, despite modifying the study protocol to minimise exposure to COVID-19 (such as offering virtual assessments), the pandemic might have negatively in uenced patient attitudes towards participating in research studies.36 There are only two other studies that have reported paediatric outcomes of children with a prenatal diagnosis of a CNV 13,37. Shi et al prospectively followed up 109 children with a prenatally diagnosed VUS up the age of 2-4 years.…”