Informed consent for expanded carrier screening: Past,present, and future

History, law, bioethics, and geocultural influences all have impacted the modern application of informed consent. It is a complex, multilayered process to communicate information and obtain voluntary patient permission before a health care intervention. Lack of provider education about genetic disorders, complexities of advanced genomic technologies, limited time during patient encounters, and low health literacy within a population all represent challenges to effective communication. There is no consensus on how informed consent in reproductive genetics is optimally obtained. Expanded carrier screening (ECS) is purposed to simultaneously test for a large list of diseases in a pan-ethnic manner. The increased use of ECS is driven by advances in genomic technologies, decreased cost, an improved understanding of single gene disorders, and in support of reproductive autonomy. Academic organizations recommend pretest counseling when patients consider ECS, yet best practice is not established. Ongoing research is needed to determine how optimally implement informed consent given the increased complexity of ECS.     

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.

     

Prenatal cystic fibrosis carrier screening: Factors in a woman's decision to decline testing

Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.     

Prenatal screening and diagnosis of congenital toxoplasmosis: a review of safety issues and psychological consequences for women who undergo screening

As part of the EUROTOXO initiative, this review focuses on the potential risks associated with prenatal testing for congenital toxoplasmosis. We first review the evidence on the risks of adverse events associated with amniocentesis, which is required for definitive diagnosis of toxoplasmosis infection in the fetus, and for which the most important risk is fetal loss. To date, there has been only one randomized trial to document risks associated with amniocentesis. This trial, which was conducted in 1986, reported a procedure-related rate of fetal loss of 1.0% (95% CI, 0.3–1.5). However, evidence from available controlled studies suggests that the pregnancy loss associated with mid-trimester amniocentesis may be lower. Potential psychological consequences of prenatal testing for congenital toxoplasmosis include parental anxiety due to false positive results and uncertainties related to prognosis of children with a prenatal diagnosis of congenital toxoplasmosis. Parental anxiety may be particularly important in screening strategies that include more frequent screenings, which may in turn entail substantial, and at times unnecessary, anxiety or other negative consequences for women and their families. These negative psychological outcomes should be balanced against the benefits of testing, which can allow women to make an informed choice regarding the pregnancy. Copyright © 2007 John Wiley & Sons, Ltd.     

Defining core outcomes of reproductive genetic carrier screening: A Delphi survey of Australian and New Zealand stakeholders

Objective

Understanding the value, benefits and harms of health interventions is needed to inform best practice and ensure responsible implementation of new approaches to patient care. Such value is demonstrated through the assessment of outcomes; however, which outcomes are assessed is often highly varied across studies and can hinder the ability to draw robust conclusions. The Core Outcome Development for Carrier Screening study aims to understand the outcomes that can meaningfully capture the value of reproductive genetic carrier screening (RGCS).

Method

The authors report an iterative, two-round online Delphi survey of Australian and New Zealand stakeholders to determine the degree of consensus regarding the core outcomes of RGCS. Panellists ranked 83 outcomes according to their perceived importance on a nine-point Likert scale. Using the distribution of rankings, outcomes were grouped into tiers representative of their perceived level of importance and agreement between groups.

Results

The top tier outcomes represent those agreed to be critically important for all future studies of RGCS to assess and were used to define a preliminary core outcome set encompassing the domains (1) primary laboratory outcomes, (2) pregnancy outcomes, (3) resource use and, (4) perceived utility of RGCS.

Conclusion

These findings can guide the selection of meaningful outcomes in studies aiming to demonstrate the value of RGCS. A future international consensus process will expand on these findings and guide the inclusion of diverse perspectives across the range of settings in which RGCS is offered.     

Attitudes to prenatal screening,diagnosis and research among pregnant women who accept or decline an alpha-fetoprotein test

The aim of the study was to describe the opinion of pregnant women who had accepted or declined an alpha-fetoprotein (AFP) test, not only on AFP screening in general, but also on whether every pregnant woman should be offered amniocentesis (AC)/chorionic villus sampling (CVS) and an ultrasound scan for fetal malformations. An additional aim was to describe pregnant women's attitudes concerning continued research in the prenatal field. The study was performed as a questionnaire study in two regions over a 1-year period from 1 October 1988 to 30 September 1989. Results are based on answers from 3331 women who had taken an AFP test and 336 women who had declined the offer of a test. A total of 79 per cent of the women thought that an AFP test, 70 per cent that an ultrasound scan for fetal malformations, and 26 per cent that AC or CVS should be offered to all pregnant women. Fifty-nine per cent of the women were positive towards continued research in the prenatal field. Women who had had an AFP test were generally much more positive towards screening and research than women who had declined, who were generally against. Women who had left school without a high school degree were on average more positive towards the screening issues than women who had this degree. In conclusion, the results obtained in this study strongly suggest that women's attitudes are very dependent on how the prenatal screening programme is already organized in their local area.