Testing Guidelines at a Glance

Evidence Lacking to Evaluate Celiac Screening
The U.S. Preventive Services Task Force (USPSTF) found there is not enough evidence to advocate for or against screening asymptomatic adults, adolescents, and children for celiac disease, according to the recommendation, published March 28 in the Journal of the American Medical Association. The standard method of diagnosing celiac disease in symptomatic patients (older than 2 years) is the tissue transglutaminase IgA test, followed by intestinal biopsy for histologic confirmation.

The finding includes a lack of evidence for targeted screening of those that are asymptomatic, but at high risk for the disease due to family history or other autoimmune disorders. USPSTF reports inadequate evidence regarding the accuracy, effectiveness, and benefits/harms of screening with regard to morbidity, mortality, or quality of life. USPSTF suggests the need for future studies, particularly in high-risk populations, that randomly assign participants to screening or no screening to evaluate clinical outcomes.

Consensus Diagnosis Recommendations for Congenital Cytomegalovirus Infection
An informal International Congenital Cytomegalovirus Recommendations Group recently published consensus guidelines in The Lancet Infectious Disease against universal screening of mothers for primary infection. The group recommended "consideration" of universal neonatal screening for cytomegalovirus to facilitate early detection and intervention to minimize long-term, adverse outcomes. Given that congenital cytomegalovirus is a frequent, but under-recognized, infectious cause of newborn malformation in developed countries, the group made recommendations for testing in limited cases:

• When a pregnant woman develops an illness with influenza-like symptoms (fever, fatigue, and headache) not attributable to another specific infection, or when imaging findings suggest fetal cytomegalovirus infection, serology tests (cytomegalovirus-specific IgG, IgM, and IgG avidity) should be offered.

• In cytomegalovirus-seronegative pregnant women, the diagnostic assessment of primary cytomegalovirus infection should include cytomegalovirus-specific IgG in serum.

• If pre-pregnancy immune status is unknown, the diagnosis of maternal primary cytomegalovirus infection should be based on detection of both cytomegalovirus IgM and cytomegalovirus IgG antibodies of low-to-moderate avidity.

• Fetal cytomegalovirus infection can be made after 20–21 weeks of gestation, and at least 6 weeks from the time of maternal infection, through nucleic acid testing (e.g., real-time polymerase chain reaction [PCR]) of amniotic fluid.

• Diagnosis in neonates should include real- time PCR, preferably of saliva, within the first 3 weeks of life.

Validation of Next-Generation Sequencing–Based Oncology Panels
A joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists published in the Journal of Molecular Diagnostics provides assistance to clinical laboratories with the validation and ongoing monitoring of next-generation sequencing-based testing for detection of somatic variants. The guideline seeks to ensure high quality of sequencing results of targeted gene panels and their diagnostic use in solid tumors and hematological malignancies.

Topics covered in the consensus recommendations include: next-generation sequencing-based test development, optimization, and validation. Specifically, it includes recommendations on panel content selection, utilization of reference materials for evaluation of assay performance, determining of positive percentage agreement and positive predictive value for each variant type, and requirements for minimal depth of coverage and minimum number of samples that should be used to establish test performance characteristics. The recommendations also discuss quality control metrics.