Prenatal Genetic Diagnosis
Conditions
Keywords
Genome Sequencing
Brief summary
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.
Detailed description
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.
Interventions
GENETICGenome Sequencing (GS)
Genome sequencing (GS) is a genetic test that involves reading the genome to identify genetic changes (also known as "genetic variants") that can cause differences in human development and disease.
Sponsors
Columbia University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Genomic Frequency | Baseline to 12 months postpartum. | The incremental frequency of fetal genetic conditions identified and reported by genomic sequencing (GS) compared to those found by standard-of-care (SOC) testing, including pathogenic, likely pathogenic, or variant of uncertain significance (VUS) variants identified by sequencing and deemed reportable by the Variant Adjudication Committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently | Baseline to 12 months postpartum. | — |
| Percent and type of P/LP findings reported | Baseline to 12 months postpartum. | — |
| Percent of fetal P/LP findings requiring adjudication | Baseline to 12 months postpartum. | — |
| Turnaround time of SOC and GS testing | Baseline to 12 months postpartum. | — |
| Frequency of reportable genomic findings in mother | 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 | Baseline to 12 months postpartum. | — |
| Frequency of participants electing to undergo standard vs tiered reporting | Baseline to 12 months Postpartum | — |
| Comparison of the demographic characteristics between these two groups | Baseline to 12 month Postpartum | — |
| Frequency of participants opting in to reporting of strong variants of uncertain Significance | Baseline to 12 month postpartum | — |
| Frequency and type of strong VUS results amongst people who opt in to receiving them | Baseline to 12 month postpartum | — |
| Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS | 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 | Baseline to 12 month postpartum | — |
| Frequency of participants opting out of reporting on copy number variants associated with susceptibility to neurodevelopmental disorders | Baseline to 12 months postpartum | — |
| Comparison of demographic characteristics between those who opt in and those who opt out of receiving susceptibility CNV results | Baseline to 12 month postpartum | — |
| Frequency of participants opting in to receive results for conditions up to and including age 18 | Baseline to 12 months postpartum | — |
| Frequency of reportable findings that may cause symptom presentation at any point during childhood (up to and including age 18) amongst those who opt in | Baseline to 12 months postpartum | — |
| Comparison of the demographic characteristics between those who opt in to receive results with possible symptom presentation up to and including age 18 vs those who elect only reporting of variants with symptom presentation up to and including only age 7 | Baseline to 12 months postpartum | — |
| Frequency of participants electing to receive secondary findings per ACMG (American College of Medical Genetics) criteria | Baseline to 12 months postpartum | — |
| Frequency of ACMG secondary findings amongst those who opt in | Baseline to 12 months postpartum | — |
| Frequency of ACMG secondary findings that would have been reported regardless of this option given immediate implications for maternal health in the peripartum period | Baseline to 12 months postpartum | — |
| Comparison of the demographic characteristics between those electing to receive ACMG secondary findings vs those declining | Baseline to 12 months postpartum | — |
| Pairwise correlations of each of the four-tiered consenting decisions | Baseline to 12 months postpartum | Pairwise correlations will be evaluated using responses collected through the structured consent administered at enrollment Outcome measures will include the proportion (%) of participants selecting each consent option and correlation coefficients describing relationships between consent decisions across tiers. |
| Frequency of false positive and negative GS results as assessed by one year of age | Baseline to 12 months postpartum | — |
Countries
United States
Contacts
CONTACTCamila Zarate, MPH
CONTACTJessica Giordano, MS, CGC
PRINCIPAL_INVESTIGATORRonald Wapner, MD
Columbia University Irving Medical Center (CUIMC)
Outcome results
None listed