This study is enrolling pregnant persons treated at Rady Children's Hospital fetal cardiology program with a prenatal diagnosis of congenital heart disease to look for genetic disorders in the fetus or unborn baby.
Congenital heart disease (CHD) is a group of structural differences to the heart that represent the most common birth defect among liveborn infants world-wide. CHD is the leading cause of birth-defect associated infant death. Prenatal detection allows for delivery planning, postnatal repair, specialized medications, and detailed counseling for parents. Up to one in three fetuses with CHD may have a genetic cause. In babies, knowing about genetic diseases helps patients and doctors provide the best care for their babies. If identified prenatally, this same knowledge may help participants prepare for their location of delivery, meet with specialists, and consider specialized treatments and medications that may be appropriate.
The diagnostic yield and clinical utility of whole genome sequencing (WGS) in fetuses with prenatally detected congenital heart disease (CHD) will be compared to routine clinical testing in patients choosing amniocentesis or chorionic villus sampling. DNA will be obtained from fetal samples and biological parent blood samples and analyzed according to standard clinical interpretation guidelines. Results will be reported to healthcare providers and patients and measures of clinical utility will be collected. Additionally, measures of stress, anxiety, depression, and perceived utility of information will be assessed by validated survey tools. A historical cohort of patients electing for diagnostic procedures will be used as a comparison population.
Pregnant individual with ongoing pregnancy with prenatally detected fetal CHD
Desire for genetic diagnosis and clinical plan for amniocentesis or chorionic villus sampling
Gestational age of 38 weeks or greater
Clinical course entirely explained by known chromosomal abnormality or confirmed genetic diagnosis that explains the clinical condition
Pregnant persons under 18 years of age
Single group
Whole Genome Sequencing (WGC) from subject samples
Diagnostic testPerform whole genome sequencing (WGS) on fetuses with prenatally detected congenital heart disease (CHD) who meet inclusion criteria. Assess diagnostic yield of WGS in CHD and effect of prenatal versus postnatal phenotype on diagnostic yield.
Diagnostic yield of WGS in fetal congenital heart disease
Trios with pathogenic or likely pathogenic sequencing results/ total number of trios.
Diagnostic yield by type of CHD lesion
As with primary outcome, diagnostic yield subcategorized into valvular defects, atrial and ventricular septal defects, inflow, and outflow tract anomalies
Patient utility of WGS as measured by: The Genome Empowerment Scale (GEmS)
Used to measure the psychological impact and personal empowerment of receiving genomic test results in a wide range of clinical conditions. GEmS consists of 28 items and four derived factors. The four factors appear to assess the following dimensions: Factor 1 - Meaning of a diagnosis (parental perception of the utility of the genomic sequencing and importance of the resulting information); Factor 2 - Emotional management of the process (parental confidence in their ability to manage emotions related to the diagnostic process and outcome); Factor 3 - Seeking information and support (parental confidence in their ability to take the next steps to find new information and support); and Factor 4 - Implications and Planning (seeking health provider support and importance of information for family reproductive decisions). The higher the factor score, the stronger the participant is in each assessed dimension.
Patient utility of WGS as measured by: The Feelings About genomiC Testing Results (FACToR) Questionnaire
Scored previously published, validated tools designed to be a brief, sensitive, and patient-centered. Used to measure the psychological impact and personal empowerment of receiving genomic test results in a wide range of clinical conditions. The instrument includes 12 items and 4 subscales (negative emotions, positive emotions, uncertainty, privacy concerns) with a 5-point Likert scale. 0=not at all, 1=a little, 2=somewhat, 3=a good deal, 4=a great deal.
Provider utility of WGS: Clinician-reported Genetic testing Utility InDEx (C-Guide)
Scored, previously published metric to assess clinical utility of genetic testing in clinical practice. Of the 30 C-GUIDE items, 27 are scored from 0 to 2 and three are scored from -2 to 0 using item-specific fixed response options. An item score \>0 indicates positive utility, an item scores \<0 indicates negative utility ("disutility"), and item scores of 0 indicate no utility. Possible C-GUIDE total scores for each scoring strategy range from -2 to 32 for each PV, -4 to 48 for one PV plus one SV, and -6 to 54 for one PV plus one SV plus one PGx cluster. C-GUIDE is an ordinal scale and items are not weighted.
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