253: Concurrent anomalies in fetuses with congenital diaphragmatic hernia and the association with copy number variants

Abstract

Among fetuses with congenital diaphragmatic hernia (CDH), the rates of concurrent anomalies and associated copy number variants (CNV) have not been well described. Our objective was to examine the rates of prenatally detected concurrent anomalies and associated CNVs among a diverse cohort of CDH cases. Retrospective cohort study of singleton prenatal CDH cases that were evaluated through one of the 5 University of California Fetal-Maternal Consortium (UCfC) sites (Davis, Irvine, Los Angeles, San Diego, San Francisco) from 2008 to 2016. Prenatally detected concurrent anomalies were categorized as cardiovascular (CV), central nervous system (CNS)/spinal, craniofacial, gastrointestinal (GI), genitourinary (GU), pulmonary, extremities, and hydrops. CNVs were categorized into 3 groups: normal, variant of uncertain significance (VUS), and pathogenic/likely pathogenic. Fisher’s exact and Chi square tests were used as appropriate to compare CMA findings by categories of associated anomalies. Logistic regression was utilized for multivariate analyses. 232 fetuses with CDH were identified; 168 (72.4%) were isolated, 64 (27.5%) had ≥1 concurrent anomaly, and 34 (14.7%) had ≥2 concurrent anomalies. Among those with additional anomalies, 35 (16.4%) were CV, 16 (6.9%) were CNS/spinal, 3 (1.3%) were craniofacial, 3 (1.3%) were GI, 14 (6.0%) were GU, 5 (2.2%) were pulmonary, 25 (10.8%) involved extremities and 8 (3.6%) had hydrops. Of the total cohort, 82 had a pre- or postnatal chromosomal microarray (CMA) performed. Of these, 63 (76.8%) were normal, 11 (13.4%) had a VUS, and 8 (9.8%) had a pathogenic or likely pathogenic CNV. Table 1 shows CMA findings by category of concurrent anomaly, comparing cases with 1 concurrent anomaly to those without. The only category significantly associated with pathogenic microarray results compared to fetuses with isolated CDH was CV anomalies (p = 0.02). Among fetuses with CDH, the most frequent concurrent anomaly was CV (16.4%), the least frequent was craniofacial (1.3%) and GI (1.3%). Cases with CV anomalies were significantly more likely, while cases with ≥2 concurrent anomalies were not significantly more likely to have pathogenic CNVs than those with isolated CDH. This information can be helpful in prenatal counseling of patients with a fetal CDH.