Genomic Microarray in Fetuses with Early Growth Restriction: A Multicenter Study

Abstract

Background: Little information is available about the risk of microdeletion and microduplication syndromes in fetal growth restriction (FGR) with a normal karyotype. Objective: To assess the incremental yield of genomic microarray over conventional karyotyping in fetuses with early growth restriction. Study Design: Genomic microarray was prospectively performed in fetuses with early growth restriction defined as a fetal weight below the 3rd percentile estimated before 32 weeks of pregnancy, and a normal quantitative fluorescent polymerase chain reaction result. The incremental yield of genomic microarray was defined by the rate of fetuses presenting with a pathogenic copy number variant below 10 Mb. Results: Among 133 fetuses with early FGR, a 6.8% (95% CI: 2.5-11.0) incremental yield of genomic microarray over karyotyping was observed. This incremental yield was 4.8% (95% CI: 0.2-9.3) in isolated FGR, 10% (95% CI: 0-20.7) in FGR with nonstructural anomalies, and 10.5% (95% CI: 0-24.3) in FGR with structural anomalies. Conclusion: Our multicenter study reveals that 6.8% of fetuses with early growth restriction present with submicroscopic anomalies after common aneuploidies were excluded. Even when FGR is observed as an isolated finding, genomic microarray analysis should be considered after or instead of karyotyping, due to its 4.8% incremental yield.

Chromosomal Microarray Analysis in Fetuses with Growth Restriction and Normal Karyotype: A Systematic Review and Meta-Analysis

“…Table 1 displays the characteristics of the 10 studies, including the overall criteria for cases being included in the studies, criteria for undergoing CMA, and the type of microarray used in the study. FGR definition was provided in 5 studies, and the cutoffs used were the 10th percentile for the estimated fetal weight in 3 studies [3,8,22], the 3rd percentile for the estimated fetal weight in 1 study [13], and the 5th percentile for the abdominal circumference in 1 study [9]. Four studies included only fetuses with FGR, 4 studies included fetuses with different ultrasound anomalies, and the remaining 2 studies also included pregnancies with advanced maternal age and abnormal serum screening.…”

“…The larger series included 115 nonmalformed and 136 malformed fetuses and reported 3 and 10% incremental yield for each FGR group, respectively [10]. The Barcelona Multicenter Study was the second larger series, with 114 nonmalformed and 19 malformed FGR fetuses, reporting a 6% and a 10% incremental yield, respectively [13]. Two further cohorts, including 65 and 45 nonmalformed FGR fetuses, reported a 2-7% incremental yield [8,9].…”

“…The most frequently encountered pathogenic imbalances were five 22q11.2 microduplication syndromes [3,8,9,13], three Xp22.3 [11][12][13] deletion syndromes, and three Williams-Beuren syndromes (7q11.23 microdeletion) [8,11,13]. Three of the 22q11.2 duplicated regions were reciprocal to the DiGeorge/velocardiofacial syndrome recurrent deletions, one was a more distal 22q11.22q11.23 microduplication [13], and in the last no details were given by the authors [9].…”

“…Three of the 22q11.2 duplicated regions were reciprocal to the DiGeorge/velocardiofacial syndrome recurrent deletions, one was a more distal 22q11.22q11.23 microduplication [13], and in the last no details were given by the authors [9]. Reciprocal microdeletion and microduplication syndromes are expected to share some clinical features, and both 22q11.2 microdeletion and microduplication syndromes may present with FGR and learning difficulties [23,24].…”

Chromosomal Microarray and Fetal Growth Restriction

“…In a recent analysis of 245 fetuses with a size below the 3rd percentile between 22 and 26 weeks, Lawin-O'Brien and colleagues [3] used abnormal uterine artery Doppler (uterine artery pulsatility index above 95th percentile and/or bilateral notches) to identify cases most likely associated with placental insufficiency.The contribution of uterine artery Doppler in identifying "pure" placental FGR as opposed to FGR associated with genetic abnormalities is unclear: first-trimester uterine artery pulsatility index is only mildly increased in pregnancies with fetusDear Editor,We would like to congratulate Dr. Borrell and colleagues for their interesting article on the use of chromosomal microarray in fetuses with growth restriction (FGR) [1] . In a cohort of 133 with FGR, they reported a 6.8% incremental yield of microarray over conventional karyotyping, ranging from 4.8% in isolated FGR to 10.5% in FGR with structural anomalies.…”