267 Multiple fetal anomalies are associated with actionable postnatal genome sequencing results

Abstract

Prenatal whole exome sequencing (WES) and whole genome sequencing (WGS) have not been adopted into routine obstetrical practice due to high cost and suspected low diagnostic yield. However, the actual diagnostic yield of these methods in pregnancies with specific prenatal findings is not known. The goal of this study is to determine whether specific types of prenatal complications are associated with actionable postnatal WES/WGS results. This is a case control study comparing critically ill neonates in the NSIGHT2 study who had actionable versus negative postnatal WES/WGS results. We excluded neonates without available prenatal ultrasound reports. We reviewed the ultrasound reports for abnormal findings. We calculated the odds ratio and used Fisher’s exact test to compare findings between the two groups. 213 neonates were sequenced in the NSIGHT2 study. 80 of those neonates had available prenatal ultrasounds. Of these, 21 had an actionable finding from genome sequencing: 7 WES and 14 WGS. 59 neonates had negative sequencing results: 32 WES and 27 WGS. 66.7% of neonates with actionable WES/WGS results had anomalies suspected on fetal ultrasound, while 55.9% of neonates with negative sequencing had suspected fetal anomalies. Among those with suspected fetal anomalies, neonates with actionable WES/WGS results were 4.5 times more likely to have multiple anomalies and 6.7 times more likely to have anomalies of the extremities compared to those with negative findings. Fetal growth restriction was present in 19% of neonates with actionable WES/WGS and in 6.8% with negative sequencing results. In our study population, neonates with actionable findings on WES/WGS were statistically more likely to have multiple anomalies and anomalies of the extremities. These findings suggest that pregnancies with multiple fetal anomalies on ultrasound may benefit from WES/WGS. Larger studies are needed to determine utility of introducing WES/WGS to clinical practice.