From diagnostic yield to clinical impact: a pilot study on the implementation of prenatal exome sequencing in routine care

Purpose Exome sequencing (ES) is an efficient tool to diagnose genetic disorders postnatally. Recent studies show that it may have a considerable diagnostic yield in fetuses with structural anomalies on ultrasound. We report on the clinical impact of the implementation of prenatal ES (pES) for ongoing pregnancies in routine care. Methods We retrospectively analyzed the impact of pES on pregnancy outcome and pre- or perinatal management in the first 22 patients counseled for pES because of one or more structural anomalies on fetal ultrasound. Results In two cases, a diagnosis was made by chromosomal microarray analysis after ES counseling. The remaining 20 cases were divided in three groups: (1) pES to aid parental decision making ( n = 12), (2) pES in the context of late pregnancy termination requests ( n = 5), and (3) pES to guide pre- or perinatal management ( n = 3). pES had a clinical impact in 75% (9/12), 40% (2/5), and 100% (3/3) respectively, showing an overall clinical impact of pES of 70% (14/20). Conclusion We show that clinical implementation of pES is feasible and affects parental decision making or pre- and perinatal management supporting further implementation of ES in the prenatal setting.