Laboratory considerations for prenatal genetic testing

Abstract

New genetic tests have rapidly entered clinical care with little consistency in laboratory testing and reporting. Non-invasive prenatal screening using cell free DNA (cfDNA) may either screen for common aneuploidies alone or include chromosomal microdeletions. All cfDNA screening tests have false positives and false negatives, and accordingly laboratories should report positive and negative predictive values. In addition, since fetal fraction plays a significant role in the reliability of results, this should also be reported with all test results. Chromosomal microarray addresses significant clinically relevant information beyond that detected with standard karyotype testing but may, in less than one percent of cases, result in a variant of uncertain significance (VUS). Laboratories should indicate their policies for reporting these VUS findings. In addition, physicians using this testing should be aware of the advantages and disadvantages of the laboratory platforms. Whole-exome and whole-genome sequencing are just entering clinical care and issues of VUS, incidental findings, and phenotype/genotype correlations need to be investigated before these techniques enter routine clinical care.

Keywords: Genetic testing; Maternal-fetal medicine; Prenatal diagnosis; Prenatal genetics.