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

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

This study looks at whether genome sequencing should be used more routinely during pregnancy, even when ultrasounds look normal. Genome sequencing can examine nearly all of a baby's genes and may find genetic conditions that standard tests do not detect. Researchers will compare this test with current prenatal testing to see if it provides helpful information for families and doctors. The study will also explore how parents decide what kinds of genetic information they want to receive and how this information affects their experience during pregnancy. The goal is to understand whether genome sequencing can be used in a way that is helpful, responsible, and supportive for families in the future.

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.

Inclusion Criteria:

• Patient planned chorionic villus sampling (CVS) or amniocentesis in the absence of major fetal structural anomalies (minor anomalies are eligible, the HPO (Human Phenotype Ontology) will not be used by the analyst)
• Certified genetic counselor involved in care

Exclusion Criteria:

• A major structural anomaly
• Maternal or paternal age less than 18 years old
• Parental unwillingness to participate in 1 year of postnatal follow-up
• Language barrier (non-English or Spanish speaking)