Utility of expanded carrier screening in pregnancies with ultrasound abnormalities.

OBJECTIVE: Explore the utility of expanded carrier screening in evaluating heritable causes of congenital anomalies detected by prenatal ultrasound. METHOD: A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. These were used to determine if expanded carrier screening could have determined the etiology prior to delivery. Additionally, recessive and X-linked conditions on clinically available carrier screening panels were evaluated to determine the number of conditions associated with abnormal ultrasound findings. RESULTS: Our retrospective chart review found 222 patients with genetic etiologies, including eight unique autosomal recessive conditions and six X-linked conditions in the 23% who underwent exome sequencing. Of these 14 unique conditions detected, three were included on a list of 271 conditions for which screening was available in 2019 and five were included on a 500 condition panel available in 2020. A literature review was performed on the list of 271 conditions and 88 were reported to be associated with one or more ultrasound abnormalities. CONCLUSION: This study demonstrates limited but potential utility for expanded carrier screening to determine the underlying etiology of congenital anomalies.

Prenatal chromosomal microarray uptake with invasive prenatal diagnosis: How many patients take the leap?

OBJECTIVE: Characterize the uptake of chromosomal microarray analysis (CMA) among women undergoing invasive prenatal diagnosis at a large academic institution over a 4-year time period. METHODS: Retrospective database review of women who underwent invasive prenatal diagnosis via chorionic villus sampling (CVS) or amniocentesis. Entries were reviewed for demographic and clinical information. RESULTS: Nine hundred forty-six diagnostic procedures were performed at our institution over a 4-year time period including 259 CVS and 687 amniocentesis procedures. Overall, 32% elected CMA, with a significant increase in uptake over time. Women with Medicaid/CHIP insurance were more likely to elect CMA than those with private insurance (OR = 1.59, 95% CI, 1.18-2.14), while multigravida women were less likely than primigravidas to elect CMA (P = 0.003). Women with ultrasound findings were more likely to elect CMA than any other indication. Those with structural abnormalities in multiple systems (OR = 3.75, 95% CI, 1.60-8.79) or abnormalities in a single system (OR = 3.22, 95% CI, 1.47-7.05) were more likely to elect CMA than with any other types of ultrasound findings. CONCLUSION: The uptake of CMA significantly increased over a 4-year period at a large academic institution. Women with ultrasound indications, specifically structural abnormalities, are the most likely to elect CMA.