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.
Study Type
OBSERVATIONAL
Enrollment
1,042
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.
Boston Childrens Hospital
Boston, Massachusetts, United States
ACTIVE_NOT_RECRUITINGNew York Genome Center
New York, New York, United States
ACTIVE_NOT_RECRUITINGColumbia University Irving Medical Center (CUIMC)
New York, New York, United States
RECRUITINGIncremental Genomic Frequency
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
Time frame: Baseline to 12 months postpartum.
Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently
Time frame: Baseline to 12 months postpartum.
Percent and type of P/LP findings reported
Time frame: Baseline to 12 months postpartum.
Percent of fetal P/LP findings requiring adjudication
Time frame: Baseline to 12 months postpartum.
Turnaround time of SOC and GS testing
Time frame: Baseline to 12 months postpartum.
Frequency of reportable genomic findings in mother
Time frame: 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
Time frame: Baseline to 12 months postpartum.
Frequency of participants electing to undergo standard vs tiered reporting
Time frame: Baseline to 12 months Postpartum
Comparison of the demographic characteristics between these two groups
Time frame: Baseline to 12 month Postpartum
Frequency of participants opting in to reporting of strong variants of uncertain Significance
Time frame: Baseline to 12 month postpartum
Frequency and type of strong VUS results amongst people who opt in to receiving them
Time frame: Baseline to 12 month postpartum
Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS
Time frame: 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
Time frame: Baseline to 12 month postpartum
Frequency of participants opting out of reporting on copy number variants associated with susceptibility to neurodevelopmental disorders
Time frame: Baseline to 12 months postpartum
Comparison of demographic characteristics between those who opt in and those who opt out of receiving susceptibility CNV results
Time frame: Baseline to 12 month postpartum
Frequency of participants opting in to receive results for conditions up to and including age 18
Time frame: 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
Time frame: 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
Time frame: Baseline to 12 months postpartum
Frequency of participants electing to receive secondary findings per ACMG (American College of Medical Genetics) criteria
Time frame: Baseline to 12 months postpartum
Frequency of ACMG secondary findings amongst those who opt in
Time frame: 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
Time frame: Baseline to 12 months postpartum
Comparison of the demographic characteristics between those electing to receive ACMG secondary findings vs those declining
Time frame: Baseline to 12 months postpartum
Pairwise correlations of each of the four-tiered consenting decisions
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.
Time frame: Baseline to 12 months postpartum
Frequency of false positive and negative GS results as assessed by one year of age
Time frame: Baseline to 12 months postpartum
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