Uptake of genetic testing for infants with congenital heart disease: Impact of prenatal versus postnatal cardiovascular genetic counseling

Abstract

Approximately 70% of congenital heart disease (CHD) is diagnosed through prenatal screening, allowing for early assessment and intervention. Expert consensus recommends genetic testing for apparently isolated CHD (iCHD), which can provide valuable insights into potential underlying genetic diagnoses. In the prenatal setting, parents may have access to non-invasive screening options as well as diagnostic testing via amniocentesis. While some families may choose to decline amniocentesis, they may be more receptive to postnatal genetic testing as an alternative. Timing of genetic counseling (prenatal vs. postnatal) can affect parental decision-making and genetic testing uptake. The primary aim of this study was to examine postnatal genetic testing uptake among families of infants with iCHD who received prenatal versus postnatal cardiovascular genetic counseling (CVGCing). We hypothesized that families of infants with iCHD who received prenatal CVGCing would have a higher uptake of postnatal genetic testing than those who received postnatal CVGCing. A retrospective chart review was completed for infants with iCHD admitted to the Cincinnati Children's Hospital Medical Center (CCHMC) Cardiac Intensive Care Unit (CICU) between January 1, 2019, and April 30, 2023. A total of 228 infants received CVGCing from a Cardiovascular Genetic Counselor (CVGC). Seventy-six (33%) families received prenatal CVGCing and 152 (67%) were counseled postnatally. Patients receiving prenatal CVGCing were approximately four times more likely to consent for postnatal genetic testing (OR = 3.88, p = 0.03) than those who received postnatal CVGCing. Genetic testing confirmed a genetic diagnosis in 14% of infants. Positive genetic testing results included both copy number variants (70%) and single-nucleotide variants (30%). In conclusion, families of infants with iCHD who received prenatal CVGCing were significantly more likely to consent for postnatal genetic testing. Patients receiving prenatal CVGCing were able to receive results faster, meet parental goals of earlier genetic counseling access, and increase genetic testing uptake. Although expert consensus statements often recommend chromosomal microarray as a first line of genetic testing for iCHD, the yield reported in our study supports consideration of CHD gene sequencing for all infants with iCHD. Preliminary results suggest prenatal CVGCing for iCHD, with consideration of comprehensive genetic testing including copy number variant analysis and gene sequencing, should be considered standard of care.