Prenatal Genetic Diagnosis by Genomic Sequencing: A Prospective Evaluation

This proposal will perform a clinical, technical, and behavioral evaluation of Genome Sequencing (GS) to identify genetic conditions such as single gene disorders in apparently normal pregnancies as a routine addition to prenatal diagnostic testing. Women between 10- and 24-weeks’ gestation planning prenatal diagnosis for routine indications will be offered the opportunity to have GS performed in addition to the present standard of karyotype and chromosomal microarray. American College of Medical Genetics (ACMG) defined pathologic, and likely pathologic variants associated with severe and profound childhood disorders or those in which treatment or modification of care up to age 8 will be reported to enrolled families. Variants of uncertain significance meeting study criteria will be reported to parents when requested. Maternal genomic disorders with the potential to alter pregnancy, delivery or postpartum health or care will also be reported. Parents will complete psychosocial surveys prior to receiving results, after result reporting, and at one year post delivery. Parents declining sequencing will also be surveyed. Infant health will be evaluated at 1 year of age or sooner if positive results are reported. The primary outcomes will be the frequency of fetal and maternal reportable disorders by either standard of care testing or GS testing and the incremental increase and benefit of reportable disorders by GS. Parental psychosocial and behavioral characteristics of families undergoing GS will be compared to a similar population of unsequenced pregnancies. They will also be compared to patients who pursued sequencing in the setting of fetal anomalies. Using results from this study and those from our initial study sequencing anomalous pregnancies, improved techniques for routine fetal phenotype and genotype collection, aggregation, and sharing will be developed. Project Number: 2R01HD055651-16 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: RONALD WAPNER (+2 co-PIs) | Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY | Award Amount: $789,220 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 HSS-Q (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11134171