Comparison of web-based information about cell-free DNA prenatal screening: implications for differences of sex development care

ObjectiveCell-free DNA (cfDNA) prenatal screening is a commercially available noninvasive test that detects fetal genetic material in maternal blood. While expectant parents often use it for “gender” determination, there is little information about unintended consequences of testing, such as revelation of a difference of sex development (DSD). The study aimed to characterize currently available website information about cfDNA and compare the cfDNA-related content.MethodsA systematic search for websites with information about cfDNA was conducted using search terms generated by a natural language processing analysis of the results of an Amazon Mechanical Turk (MTurk) survey of 1,000 parents and then performing a “Google” search, using the terms. Commercial cfDNA testing companies (CC) websites were also identified by consulting a genetic counselor (AGW). Data were collected on about each website’s characteristics and information about cfDNA. Information about cfDNA was compared between websites. Data were analyzed using descriptive statistics, Fisher’s exact test or Kruskal-Wallis test were applied, as appropriate.ResultsSixty websites were identified. After eliminating duplicates, 11 commercial company (CC) websites were identified. Nineteen other websites were reviewed of which six overlapped with five CC websites. Most of the websites had non-professional authors (73.7%), such as laypersons and CC representatives. CC websites were significantly more likely than search term-identified websites to state that cfDNA can screen for trisomy 21 (p=0.002), trisomy 18 (p<0.0001), trisomy 13 (p<0.001), sex chromosome aneuploidies (p<0.001), and microdeletions (p=0.002).ConclusionsThis study shows that most website currently available information for expectant parents about cfDNA prenatal screening is produced by non-professional organizations. There are significant differences between the information provided by CC and Google search websites, specifically about the number of conditions screened for by cfDNA. Improving availability and quality of information about cfDNA could improve counseling future expectant parents. Inclusion of information about the potential for detection of a DSD is needed

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel

BACKGROUND: Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG). METHODS: Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene. RESULTS: Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four. CONCLUSION: This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait-based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation