Interest of chromosomal microarray analysis in the prenatal diagnosis of fetal intrauterine growth restriction

Abstract

Objective The aim of this study is to evaluate the diagnostic utility of prenatal diagnosis using the chromosomal microarray analysis (CMA) for fetuses presenting with isolated or associated intrauterine growth restriction (IUGR). Method We retrospectively included all fetuses with IUGR referred for prenatal testing and studied by rapid fluorescence in situ hybridization (FISH), karyotype, and CMA. Results Among the 162 IUGR fetuses (78 associated and 84 isolated IUGR) included, 15 had an abnormal FISH result: 10 associated and five isolated fetal IUGRs. Among the 143 fetuses studied by CMA, 10 (7%) presented pathogenic copy number variations (CNVs). All 10 were in the associated fetal IUGR group (10/65 or 15.4%; 95% confidence interval [CI]: 8.4%‐26.2%) versus 0/78 in the isolated fetal IUGR group (95% CI: 0%‐5.6%). Six fetuses (4.2%) carried variants of unknown significance (VOUS) (three associated and three isolated fetal IUGRs). Conclusion Our study highlights the added value of CMA in the case of associated fetal IUGR with an incremental yield of 6.1% (4/65) over karyotyping. No pathogenic CNVs were reported in the isolated fetal IUGR group. More studies must be conducted to determine when and whether CMA would be wisely indicated in this population.

FIGO (International Federation of Gynecology and Obstetrics) initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction

“…In addition, women should be counselled about the risk of a genetic etiology even in the presence of “isolated” FGR (i.e. without associated fetal anomalies) 37,270,283‐285 . A recent meta‐analysis of 10 studies found that in cases of isolated FGR, chromosomal microarray had an incremental yield of 4% (95% CI, 1%–6%) over karyotyping: 17 of 376 fetuses with isolated FGR and normal karyotype had significant findings in microarray, most commonly 22q11.2 duplication, Xp22.3 deletion, and 7q11.23 deletion.…”

“…37,270,[283][284][285] A recent meta-analysis of 10 studies found that in cases of isolated FGR, chromosomal microarray had…”

The Genetic and Clinical Outcomes in Fetuses With Isolated Fetal Growth Restriction: A Chinese Single-Center Retrospective Study

“…There have been few studies about what factors would influence the detection rate of CMA in fetuses with FGR. Since the commercial explosion of CMA, most studies of CMA in FGR focused on the incremental yield compared karyotype ( Borrell et al, 2018 ), as well as compared the detection rate of CMA between isolated FGR and FGR combined with other structural abnormalities ( Zhu et al, 2016 ; Borrell et al, 2017 ; Brun et al, 2018 ). There were only a few studies on isolated FGR.…”

Utility of chromosomal microarray analysis for the exploration of isolated and severe fetal growth restriction diagnosed before 24 weeks' gestation

“…24 In contrast to this literature, Brun et al did not find any additional improvement of the CMA over karyotype in the case of isolated IUGR. 25 Their selection criteria focused on the severity of the IUGR (<3rd centile) but not on its early onset. 25 We note the absence of aneuploidies in our cohort; this can be explained by the first trimester Down screening test performed for all the patients.…”

“…25 Their selection criteria focused on the severity of the IUGR (<3rd centile) but not on its early onset. 25 We note the absence of aneuploidies in our cohort; this can be explained by the first trimester Down screening test performed for all the patients. When Doppler anomalies are present, they tend to point to a vascular origin of the IUGR.…”