By Lori Solomon, Editor, Diagnostic Testing & Emerging Technologies
A new joint statement has been issued by five medical societies regarding use of expanded carrier screening in reproductive medicine. The paper, published in Obstetrics & Gynecology, does not advocate for or against the universal implementation of expanded carrier screening, but seeks to serve as an educational piece for clinicians and laboratories.
“Whether the practitioner follows current professional society recommendations or uses expanded carrier screening, the goal of preconception and prenatal carrier screening is to provide couples with information to optimize pregnancy outcomes based on their personal values and preferences,” write the authors, led by Janice G. Edwards, from the American College of Medical Genetics and Genomics (ACMG). Representatives from ACMG along with those from the American College of Obstetricians and Gynecologists (ACOG), the National Society of Genetic Counselors (NSGC), the Society for Maternal-Fetal Medicine and Perinatal Quality Foundation authored the paper.
Traditional carrier screening for inherited genetic disorders is an important part of preconception and prenatal care, the authors say, but has largely been condition-directed based on ancestry or individual conditions. Condition severity, prevalence, carrier frequency, detection rates, and residual risk also influence professional practice guidelines aimed at identifying couples at risk for passing on such genetic conditions to their offspring. Panethnic screening is currently most commonly recommended for cystic fibrosis (ACOG, ACMG, and NSGC) and spinal muscular atrophy (ACMG).
However, new technology, including genetic sequencing, is enabling more efficient carrier screening of a greater number of conditions for broader populations than are currently recommended by professional organizations. While the argument has been made that more information is better, expanded screening presents challenges in patient management, as this screening can include more than 100 genetic conditions, most of which are rare, autosomal-recessive conditions. While traditional carrier screening has focused on conditions that significantly affect quality of life, have a fetal, neonatal, or early childhood onset, and well-defined phenotype, expanded panels include additional conditions that have significant variation in the severity of their presentation and timing of onset.
While the authors believe further evaluation of reproductive outcomes resulting from expanded carrier screening and full measurement of related costs are warranted, they acknowledge that expanded screening is proceeding in practice. Given the practical considerations, the societies emphasize the need for pre-test counseling and informed consent with the use of expanded carrier screening. While pretest consultation for each tested condition is “not practical or necessary” the authors say pretest education and consent should broadly describe the types of conditions being screened for as well as the limitations of screening, including the fact that even with negative screening results “residual risk is always present, although not always quantifiable.”
For laboratories conducting expanded carrier screening, the authors recommend inclusion only of genes and variants that are well-understood; limiting reporting of variants of unknown significance; provision of residual risk estimation in laboratory reports when the carrier frequency and detection rate are both known; and that the limitations of interpretation of negative screening should be clearly communicated.
Additionally, the authors call for development of a curated data repository of variants and associated phenotypes, which they say will ultimately improve the predictive value of carrier testing if such data is available to clinicians, counselors, and investigators. “Laboratories share responsibility for collaborative analysis of expanded carrier screening to further our understanding of human mutation,” they say.
Several authors report financial ties to the molecular diagnostics industry.