Risk for aneuploidy in the structurally normal growth restricted fetus

To assess the frequency of chromosomal aneuploidy in the intrauterine growth restricted (IUGR) fetus without major structural anomalies. A retrospective analysis utilizing a reference lab database was performed for patients undergoing invasive prenatal testing between 2011 and 2017. Inclusion criteria included the documented indication for testing of IUGR. Women with major structural malformations noted on ultrasound were excluded from analysis. We analyzed the frequency of varying types of aneuploidy in our cohort, and performed a subanalysis comparing aneuploidy results for fetuses with ultrasonographic soft markers to those without soft markers. There were 1802 patients without major structural abnormalities having invasive diagnostic procedures with IUGR as the indication for testing. There were 152 (8.5%) chromosomally abnormal fetuses. Of the chromosomally abnormal fetuses, there were 72 cases of Trisomy 18 (47.3 %), 6 cases of Trisomy 13 (3.9 %), and 20 cases of Trisomy 21 (13.2%). Partial deletion and duplication syndromes accounted for 28 cases (18.4%), triploidy accounted for 21 cases (13.8%), and other rare anomalies constituted 5 cases (3.2%). When fetuses with ultrasonographic soft markers were excluded, there were 98/1595 (6.2%) chromosomally abnormal fetuses. There was a statistically significant higher proportion of chromosomally abnormal IUGR fetuses when ultrasonographic soft markers were present 54/207 (26.1%) when compared to the proportion of chromosomally abnormal IUGR fetuses without any soft markers 98/1595 (6.2%), p<0.00001. Fetuses with isolated IUGR and no major structural abnormalities have a significant risk of aneuploidy. Our data suggests that patients with isolated IUGR should be offered diagnostic testing for chromosomal assessment. Further prospective studies are needed to delineate the utility of chromosomal microarray, whole exome sequencing, and cfDNA in the assessment and etiopathogenesis of the fetus with isolated IUGR.