guideSEQ: Genomic Understanding, Impact, Decision & Ethics in Prenatal Sequencing

This multicenter, observational cohort study will evaluate prenatal sequencing among pregnancies with no fetal structural anomalies recruited at university based medical centers and evaluated at the New York Genome Center. Pregnancies with no fetal structural anomalies and meeting eligibility criteria will be enrolled into the study.

The prenatal sequencing group will be used to determine the frequency of pathogenic, likely pathogenic, and uncertain genomic variants identifiable by sequencing and the relative yield of sequencing. The prenatal sequencing group will be evaluated to understand the psychosocial needs of pregnant couples. Mothers, fathers and infants will be followed through 1 year postpartum.

The main objective of this multi-center collaborative study is to evaluate genome sequencing as a prenatal diagnostic tool in pregnancies with no known structural anomalies. Specifically, the aims are as follows:

Aim 1: Determine in pregnancies with a normal finding on ultrasound imaging, the frequency and types of fetal and maternal genetic conditions identified by GS, which impact clinical care. The goal is to understand the scope of these conditions, explore appropriate reporting criteria in pregnancy, and the role of genetic conditions in maternal morbidity and mortality.

Aim 2: Determine parental attitudes, choices, and the impact of offering prenatal whole genome sequencing as a genetic diagnostic screen in pregnancies with normal ultrasound anatomy. Clinician and community perspectives on the utility of prenatal GS as a non-invasive tool will be evaluated.

Aim 3: Expand the infrastructure for the standardized collection of prenatal genotype and phenotype data that is required to maximize future interpretive algorithms.

• Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently [Срок оценки: Baseline to 12 months postpartum.]
• Percent and type of P/LP findings reported [Срок оценки: Baseline to 12 months postpartum.]
• Percent of fetal P/LP findings requiring adjudication [Срок оценки: Baseline to 12 months postpartum.]
• Turnaround time of SOC and GS testing [Срок оценки: Baseline to 12 months postpartum.]
• Frequency of reportable genomic findings in mother [Срок оценки: Baseline to 12 months postpartum.]
• Number of specialists added to the care of the pregnancy, delivery, and newborn care (as applicable) based on the reported genetic results [Срок оценки: Baseline to 12 months postpartum.]
• Frequency of participants electing to undergo standard vs tiered reporting [Срок оценки: Baseline to 12 months Postpartum]
• Comparison of the demographic characteristics between these two groups [Срок оценки: Baseline to 12 month Postpartum]
• Frequency of participants opting in to reporting of strong variants of uncertain Significance [Срок оценки: Baseline to 12 month postpartum]
• Frequency and type of strong VUS results amongst people who opt in to receiving them [Срок оценки: Baseline to 12 month postpartum]
• Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS [Срок оценки: Baseline to 12 months postpartum]
• Comparison of the demographic characteristics between those who opt in and those who opt out of receiving strong VUS results [Срок оценки: Baseline to 12 month postpartum]