Genomic Alterations Are Enhanced in Placentas from Pregnancies with Fetal Growth Restriction and Preeclampsia: Preliminary Results

Fetal growth restriction (FGR) secondary to placental insufficiency and preeclampsia (PE) are associated with substantially increased childhood and adult morbidity and mortality. The long-term outcomes are related to placental aberrations and intrauterine programming. Advances in microarray technology allow high-resolution, genome-wide evaluation for DNA copy number variations - deletions and duplications. The aim of our study was to demonstrate the usefulness of microarray testing in FGR placentas. Using Affymetrix GeneChip for chromosomal microarray (CMA), we analyzed 10 placentas from pregnancies with FGR attributed to placental insufficiency; 5 with FGR below the 5th percentile and 5 from the 5th to <10th percentiles. All fetuses had normal anomaly scans and karyotypes. We also analyzed 5 third-trimester placentas from pregnancies complicated by PE with severe features and 5 from PE without severe features, all with appropriately grown fetuses. The results were compared to 10 placentas from uncomplicated pregnancies with healthy neonates. CMA analysis identified more genomic alterations in FGR (p < 0.05) and in PE (p < 0.05) placentas than in healthy controls. There was a correlation to the severity of FGR and PE. The genomic alterations were below the resolution of normal karyotyping. The altered genes are related to adult human height, stress reactions and to cellular migration, differentiation and adhesion. Though very preliminary, our data support evaluating FGR and PE placentas using CMA. Larger data sets are needed for further evaluation of the findings and their clinical implications.