Informed decision making and psychosocial outcomes in pregnant and nonpregnant women offered population fragile X carrier screening.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (χ2=16.98, P<0.001). Overall, informed choice was high in both nonpregnant (77.4%) and pregnant (72.9%) women (χ2=0.21, P=0.644), and more tested (76.0%) than not-tested (66.7%) women (χ2=6.35, P=0.012) made an informed choice. Measures of depression, stress, and anxiety were similar to population norms for ~85% of women. Decisional conflict and regret were generally low; however, decisional uncertainty and regret were greater in pregnant than nonpregnant women, and not-tested than tested women (uncertainty: χ2=18.51, P<0.001 and χ2=43.11, P<0.001, respectively; regret: χ2=6.61, P<0.037 and χ2=35.54, P<0.001, respectively).ConclusionWe provide evidence to inform guidelines that population FXS carrier screening can be implemented with minimal psychosocial harms following appropriate information and prescreening genetic counseling.

High school Tay-Sachs disease carrier screening: 5 to 11-year follow-up.

The Melbourne high school Tay-Sachs disease (TSD) carrier screening program began in 1997. The aim of this study was to assess the outcomes of this screening program among those who had testing more than 5 years ago, to evaluate the long-term impact of screening. A questionnaire was used for data collection and consisted of validated scales and purposively designed questions. Questionnaires were sent to all carriers and two non-carriers for each carrier who were screened in the program between 1999 and 2005. Twenty-four out of 69 (34.8 %) carriers and 30/138 (21.7 %) non-carriers completed the questionnaire. Most participants (82 %) retained good knowledge of TSD and there was no evidence of a difference in knowledge between carriers and non-carriers. Most participants (83 %) were happy with the timing and setting of screening and thought that education and screening for TSD should be offered during high school. There was no difference between carriers and non-carriers in mean scores for the State Trait Anxiety Inventory and Decision Regret Scale. This evaluation indicated that 5-11 years post high school screening, those who were screened are supportive of the program and that negative consequences are rare.

Population-based carrier screening for cystic fibrosis in Victoria: the first three years experience.

BACKGROUND: Cystic fibrosis (CF) is the most common inherited, life-shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant. AIMS: To report the outcomes of a carrier screening program for CF. METHOD: Carrier screening was offered to women and couples planning a pregnancy, or in early pregnancy, through obstetricians and general practitioners in Victoria, Australia. Samples were collected by cheek swab and posted to the laboratory. Twelve CFTR gene mutations were tested. Carriers were offered genetic counselling and partner testing. Carrier couples were offered prenatal testing by chorionic villous sampling (CVS) if pregnant. The number of people tested, carriers detected and pregnancy outcomes were recorded from January 2006 to December 2008. RESULTS: A total of 3200 individuals were screened (3000 females). One hundred and six carriers were identified (one per 30, 95% confidence interval one per 25, one per 36). All carrier partners were screened, and nine carrier couples identified (total carriers 115). Ninety-six individuals (83%) were carriers of the p.508del mutation. Of the nine carrier couples, six were pregnant at the time of screening (five natural conception and one in vitro fertilisation) and all had CVS (mean gestation 12.5 weeks). Two fetuses were affected, three were carriers and one was not a carrier. Termination of pregnancy was undertaken for the affected fetuses. CONCLUSION: Carrier screening for CF by obstetricians and general practitioners by cheek swab sample can be successfully undertaken prior to pregnancy or in the early stages of pregnancy.

Factor V Leiden mutation: a contributory factor for cerebral palsy?

Fifty-seven children with cerebral palsy (CP) and imaging evidence of vascular thrombosis (study group) and 167 children with CP and other imaging finds (control group)were selected. Sixty-one per cent of the study group were male and 53 (93%) had spastic hemiplegia compared with the control group, of whom 55% were male and 54 (32%) had a diagnosis of spastic hemiplegia. Mean age was 5 years 11 months (SD 5y 1mo) for the study group and 7 years 7 months (SD 4y 7mo) for the control group. Blood spots on Guthrie cards or buccal swabs were used to test both groups and their mothers for the factor V Leiden (fVL) mutation, which predisposes carriers to thrombophilia. Mothers were interviewed to gather antenatal, perinatal, demographic, and socio-economic data. The frequency of the fVL mutation in children with evidence of vascular thrombosis and their mothers was not statistically different from the frequency in children with CP with other imaging findings and their mothers. The frequency of the fVL mutation was significantly higher than the expected population frequency of 4% in the study group (10.5%, p=0.012) and in mothers of the control group (7.2%, p=0.036).

Complex phenotypes in the haemoglobinopathies: recommendations on screening and DNA testing.

This document considers a number of scenarios involving complex haemoglobinopathies and provides 28 recommendations at both the clinical and laboratory levels on how these should be managed.

Tay Sachs disease carrier screening in schools: educational alternatives and cheekbrush sampling.

PURPOSE: Tay Sachs disease carrier screening programs have been offered successfully worldwide since 1970. The programs typically offer education, testing, and counseling to provide reproductive choices. One such program has been offered to Jewish school students in Melbourne since 1998. In a time of increasing public awareness of genetics, programs require continuous evaluation and updating. METHODS: Over 2 successive years, a longitudinal evaluation involved students attending Jewish schools in Melbourne. Both qualitative and quantitative techniques were used to analyze alternative methods for education and sampling procedures. Comparisons involved (1) a computer-based resource versus an oral educational presentation and (2) blood sampling for enzyme and genetic testing versus cheekbrush testing for genetic sampling alone. RESULTS: The education session was effective in significantly increasing students' knowledge (10.5% +/- 1.2%, P < .0001) and decreasing their anxiety about being a carrier (-12.2% +/- 1.6%, P < .0001). For the students, no significant differences were found between the computer-based resource and oral presentation. There were significantly more students accepting a carrier test and anxiety was lower when a cheekbrush test was offered compared with when a blood test was offered. CONCLUSIONS: Computer-based instruction is equally effective, in addition to offering advantages of self-paced learning and minimization of human resources as an oral presentation within a genetic carrier screening program. Cheekbrush sampling is preferred to blood sampling and should be implemented into current practices for offering genetic screening programs. These results present alternatives to practices for genetic screening reflecting the current developing technology.