Evaluating the efficacy of three carrier screening workflows designed to identify at‐risk carrier couples

Abstract

Objective: To evaluate the efficacy of three different carrier screening workflows designed to identify couples at risk for having offspring with autosomal recessive conditions.Methods: Partner testing compliance, unnecessary testing, turnaround time, and ability to identify at-risk couples (ARCs) were measured across all three screening strategies (sequential, tandem, or tandem reflex).Results: A total of 314,100 individuals who underwent carrier screening were analyzed. Sequential, tandem, and tandem reflex screening yielded compliance frequencies of 25.8%, 100%, and 95.9%, respectively. Among 14,595 couples tested in tandem, 42.2% of females were screen-negative, resulting in unnecessary testing of the male partner. In contrast, less than 1% of tandem reflex couples included unnecessary male testing. The median turnaround times were 29.2 days (sequential), 8 days (tandem), and 13.3 days (tandem reflex). The proportion of ARCs detected per total number of individual screens were 0.5% for sequential testing and 1.3% for both tandem and tandem reflex testing. Conclusion:The tandem reflex strategy simplifies a potentially complex clinical scenario by providing a mechanism by which providers can maximize partner compliance and the detection of at-risk couples while minimizing workflow burden and unnecessary testing and is more efficacious than both sequential and tandem screening strategies. Highlights What's already known about this topic?� Studies have explored barriers to carrier screening and follow up partner testing to identify at-risk couples. However, to date, no one has explored the efficacy of different carrier screening workflows.Ben-Shachar and Johansen Taber are co-senior authors.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

An Ethical Argument for Health Insurance Coverage of Paternal Prenatal Genetic Testing

“…For example, research has shown that tandem reflex screening, compared with sequential screening, improves partner testing adherence up to fourfold and still avoids unnecessary partner testing in pregnant patients with negative screen results. 13 Second, there is a shortage of genetic counselors, so workforce constraints must be taken into consideration as tandem testing programs are implemented. Third, given gestational age–based limits to and restrictions on abortion in some states after the Dobbs v Jackson Women's Health Organization ruling, some clinicians and insurance companies might view the loss of abortion access as a reason to restrict prenatal genetic testing.…”

Every mother and every fetus matters: A positive pregnancy test = multiple offerings of reproductive risk screening for personal, family, and specific obstetrical‐fetal conditions

“…Genetic carrier screening is genetically and ethically complex. An important clinical counseling consideration is that 70% of individuals will be “screen positive” for one or more genetic conditions and that 1 in every 40 couples will test positive for the same genetic condition using an expanded carrier screening platform 26,99,100 . Some personal considerations for early embryo‐fetal identification, using the expanded genetic carrier screen, would include that some genetic conditions have improved childhood outcomes with early intervention, some carry a risk for childhood intellectual disability, and some will have limited or no treatment options for the fetus/child 101‐103 …”

“…An important clinical counseling consideration is that 70% of individuals will be "screen positive" for one or more genetic conditions and that 1 in every 40 couples will test positive for the same genetic condition using an expanded carrier screening platform. 26,99,100 Some personal considerations for early embryo-fetal identification, using the expanded genetic carrier screen, would include that some genetic conditions have improved childhood outcomes with early intervention, some carry a risk for childhood intellectual disability, and some will have limited or no treatment options for the fetus/child. [101][102][103] Direct to consumer medical testing for disease risk has created new questions, expectations, and concerns for the medical provider, who did not order the test or provide any risk-benefit counseling for patient/couple's informed consent.…”

Expanded carrier screening for reproductive risk assessment: An evidence‐based practice guideline from the National Society of Genetic Counselors

“…Several factors appear to influence the likelihood of partner testing completion, including disease severity for the positive result (Jurgensmeyer et al, 2021;Shapiro et al, 2021) and presence of the partner at the initial ECS appointment (Jurgensmeyer et al, 2021). While some individuals may decline partner testing as the information would not change their reproductive management, prior studies have identified this attitude is generally held by a minority (33.3%) of patients (Shapiro et al, 2021) (Arjunan et al, 2021).…”