Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome.

OBJECTIVE: To 'map' the current (2004) state of prenatal screening in Europe. DESIGN: (i) Survey of country policies and (ii) analysis of data from EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers. SETTING: Europe. POPULATION: Survey of prenatal screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down's syndrome screening and 14/18 for structural anomaly scanning. Sixty-eight percent of Down's syndrome cases (range 0-95%) were detected prenatally, of which 88% resulted in termination of pregnancy. Eighty-eight percent (range 25-94%) of cases of NTD were prenatally detected, of which 88% resulted in termination. Countries with a first-trimester screening policy had the highest proportion of prenatally diagnosed Down's syndrome cases. Countries with no official national Down's syndrome screening or structural anomaly scan policy had the lowest proportion of prenatally diagnosed Down's syndrome and NTD cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors, are associated with wide country variation in prenatal detection rates for Down's syndrome and NTD.

Attitudes toward colon cancer gene testing: survey of relatives of colon cancer patients.

OBJECTIVES: Various studies have identified psychosocial factors that may influence attitudes toward colon cancer gene testing. Whereas family history of colon cancer has been associated with interest in gene testing, this has not been examined extensively. We hypothesized that the strength of family history of colon cancer is associated with risk perception and willingness to undergo gene testing. MATERIALS AND METHODS: We evaluated attitudes toward colon cancer gene testing among persons who had at least one first-degree relative with colon cancer. A total of 2680 at-risk relatives in 863 kindreds were identified and mailed an extensive survey regarding sociodemographic variables, family history, health behaviors and knowledge, and willingness to take a colon cancer gene test. A total of 56.6% of persons completed and returned surveys. We conducted a brief telephone survey of a random sample of 200 persons who did not respond to the mail survey. RESULTS: The combined study sample of 1373 people was 42% male, had a mean age of 55 +/- 15 years, was 96% white, and had moderate-to-high SES. A total of 77.4% were very likely to take the gene test, and 92.4% were somewhat or very likely to take the gene test. A total of 78% of the sample perceived a higher colon cancer risk, although patterns of risk perception and worry differed significantly between mail survey and telephone survey respondents. More of the telephone survey respondents were also somewhat unlikely or very unlikely to take the gene test compared to the mail survey respondents (13.7% versus 6.9%). In the combined sample, concern about developing colon cancer and risk perception increased with number of relatives with colon cancer (P < 0.0001). Eight percent expressed no concern about developing colon cancer; 4.8% felt their chance of developing colon cancer was lower than others of the same age, sex, and race; and 3.3% felt that they were very unlikely to develop colon cancer in their lifetime. However, there was strong interest in gene testing regardless of the number of affected relatives, and persons with more affected relatives were generally willing to pay more for the gene test (up to $1000). CONCLUSIONS: The strength of family history of colon cancer is associated with risk perception but not with willingness to undergo gene testing.

Using decision analysis to compare policies for antenatal screening for Down's syndrome.

OBJECTIVE: To compare different screening policies for Down's syndrome across a broad range of outcomes, using decision analysis, with particular reference to the role of maternal serum testing. DESIGN: A decision tree was used to combine data from local sources and the medical literature to predict the likely frequency of several outcomes. Sensitivity analyses were used to test the robustness of the conclusions drawn. SETTING: Oxfordshire Health Authority. MAIN OUTCOME MEASURES: Live births with and without Down's syndrome; miscarriages with Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses performed (and associated miscarriages); direct NHS screening costs; number of women offered screening. RESULTS: Screening policies for Down's syndrome that include serum testing can produce better population outcomes than programmes that do not. Each option for screening for Down's syndrome that we considered had significant drawbacks. In Oxfordshire, offering serum testing to women of all ages would prevent the birth of approximately one more baby with Down's syndrome per year than would a policy of screening for women aged 30 years or more. The cost of preventing this one extra Down's birth would be one or two normal babies lost after amniocentesis, 4500 blood tests for young women (with the associated anxiety and counselling), approximately 200 false positive serum test results and amniocenteses (with the associated anxiety and distress), and 90,000 pounds for the extra tests, counselling, and amniocenteses. Opinions are divided as to which policy is the better option for the population. CONCLUSIONS: Decision analysis is a useful tool for determining the likely consequences of different policy options across a broad range of outcomes. This focuses debate and decision making on outcomes of care, which in turn makes it clear that the choice of screening programme for Down's syndrome depends on the relative importance ascribed to the different outcomes. If individuals' values vary widely it may be impossible to find one screening policy that meets the needs of all pregnant women.

Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening.

BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice. METHODS: We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known. RESULTS: If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices.

An economic appraisal of alternative pre-natal screening programmes for Down's syndrome.

The objective of this study was to evaluate economically a screening programme within the Oxford Regional Health Authority for Down's syndrome, based on maternal serum alpha fetoprotein, unconjugated oestriol and human chorionic gonadotrophin as well as maternal age (the triple test) against maternal age alone. The design of the study involved cost-effectiveness analysis of the triple test relative to the maternal age screening programme, and the main outcome measure was the cost per Down's birth avoided. It was found that the triple test is more cost-effective over a wide range of assumptions concerning detection rates and procedure costs. Indirect costs are important in considering the cost-effectiveness of the screening programmes. The most efficient detection rate is around 58 per cent for which the cost per Down's birth avoided is approximately 29,600 pounds if only direct costs are evaluated, 20,100 pounds if all NHS costs are considered and -49,800 pounds if all resource consequences are analysed. It may be concluded that screening for Down's syndrome using the triple test is cost-effective over a wide range of assumptions concerning detection rate and procedure costs. If all resource costs are considered, the programme is highly cost-effective in comparison with other health care interventions.