Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

OBJECTIVES--To assess the implementation of antenatal screening for Down''s syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN--Demonstration project of Down''s syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING--Hospital and community antenatal clinics in four health districts in London. SUBJECTS--12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES--Uptake of screening, detection rate for Down''s syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS--The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down''s syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION--Antenatal maternal serum screening for Down''s syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.     

Serum screening for Down's syndrome: some women's experiences.

OBJECTIVES--To describe the experiences of a small group of women who had positive results after serum screening for Down''s syndrome. DESIGN--Semistructured telephone interviews and correspondence with women after a positive screening result (four women) negative amniocentesis results (eight), or termination of a pregnancy with a confirmed abnormality (eight). SUBJECTS--20 women who contacted Support After Termination For Abnormality about their experiences of serum screening for Down''s syndrome. MAIN OUTCOME MEASURES--Women''s knowledge and understanding of the test; staff misconceptions; communication of results; how women coped with the diagnostic process; attitudes to the test and to termination of abnormal fetuses. RESULTS--All women were made anxious by their positive screening test, no matter how they were told. The women''s experiences suggested that medical staff were unclear about the implications of screening tests and how to interpret risk. Even after receipt of negative amniocentesis results some women remained anxious. Staff did not always recognise women''s concerns while awaiting amniocentesis results. CONCLUSIONS--The way in which serum screening is being implemented does not always meet the needs of women with positive results. Some of the problems were not specific to screening for Down''s syndrome. When screening tests are introduced policies should be adopted to ensure appropriate support for participants.     

Maternal serum screening for Down's syndrome in early pregnancy.

The possibility of improving the effectiveness of antenatal screening for Down''s syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down''s syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down''s syndrome in the United Kingdom from about 900 a year to about 350 a year.     

Screening for Down's syndrome based on individual risk.

OBJECTIVE--To evaluate the effectiveness of biochemical screening of individual pregnancies for Down''s syndrome risk. DESIGN--Retrospective determination of risk. SETTING--Obstetric and cytogenetic services in Tayside, Scotland. SUBJECTS--3436 pregnant women who had screening for neural tube defects in the second trimester during November 1988 to March 1990 and whose pregnancies were dated by ultrasonography. Three women with pregnancies associated with Down''s syndrome reported later in 1990. MAIN OUTCOME MEASURES--Individual risk calculated from age at estimated date of delivery; chorionic gonadotrophin and alpha fetoprotein concentrations in serum samples obtained at precisely determined gestational ages in second trimester. Results of karyotype determination and outcome of pregnancy. RESULTS--During November 1988 to March 1990 karyotypes were determined for 5% of pregnancies for reasons of maternal age and genetic history and one of the eight affected fetuses was detected. Individual risk could not be calculated for 347 pregnancies, but screening on this basis would have detected five of the cases and required screening in 194 out of 3089 (6.3%) pregnancies; all three affected pregnancies reported later in 1990 would also have been detected, giving a success rate of 73% (95% confidence interval 39% to 94%). The age distribution of women according to individual risk suggests that women over 35 would be screened effectively. CONCLUSION--Screening based on individual risk would use resources more effectively than screening based on maternal age and genetic history without affecting detection rates in older women.     

Measurement of activity of urea resistant neutrophil alkaline phosphatase as an antenatal screening test for Down's syndrome.

OBJECTIVE--To investigate the value of measuring maternal urea resistant neutrophil alkaline phosphatase activity as an antenatal screening test for Down''s syndrome. DESIGN--Case-control study of blood samples collected at nine to 27 weeks of pregnancy. SETTING--Antenatal clinics in London and Oxford. PATIENTS--72 Women whose fetuses had been diagnosed by amniocentesis or chorionic villus sampling as having Down''s syndrome and 156 women whose fetuses did not have the syndrome. Only singleton pregnancies were studied. MAIN OUTCOME MEASURE--Activity of urea resistant neutrophil alkaline phosphatase measured cytochemically. RESULTS--The median enzyme activity in the index patients was 1.65 times the expected median for the controls at the same duration of pregnancy (p less than 0.0001; 95% confidence interval 1.56 to 1.74). A cut off value that identified the 5% of control patients with the highest activities yielded a rate of detection of Down''s syndrome of 79% (95% confidence interval 70 to 89%). CONCLUSION--Activity of urea resistant neutrophil alkaline phosphatase is an effective maternal blood marker for Down''s syndrome. Its use in antenatal screening could lead to a substantial improvement in the detection of this disorder. Before introducing the test into routine medical practice it will have to be automated so that it can be used on a large scale and is less subjective.     

Screening for Down's syndrome in the North East Thames region.

The suggested strategies for a screening programme for Down''s syndrome by maternal serum alpha fetoprotein concentration were examined and tested on the experience of the North East Thames Regional. Screening by maternal serum alpha fetoprotein concentration may be used to identify pregnancies at increased risk, but this is useful only in women aged over 32 whose collective risk is greater than one in 200. The absolute probability of carrying babies with Down''s syndrome for individuals in this high risk group can then be calculated and used to decide whether further diagnosis by amniocentesis is desired.     

Retrospective audit of different antenatal screening policies for Down's syndrome in eight district general hospitals in one health region

ObjectiveTo compare the effectiveness of different screening policies for the antenatal detection of Down''s syndrome.DesignRetrospective six year survey.SettingMaternity units of eight districts.ParticipantsWomen who completed their pregnancies between 1 January 1994 and 31 December 1999 (155 501 deliveries).Results335 cases of Down''s syndrome were identified, 323 in continuing pregnancies or liveborn children. Of these, 171 were identified antenatally. Seven different screening policies were used, in three principal groups: serum screening offered to all mothers, maternal age with serum screening or nuchal translucency available to limited groups, and maternal age combined with anomaly scans. The districts that used serum screening detected 57%, those using maternal age plus serum or nuchal translucency screening 52%, and those using a maternal age of ⩾35 and anomaly scans detected 54%. The least successful district, which offered amniocentesis only to women aged over 37 years, detected only 31%. If amniocentesis had been offered from 35 years, as in all other districts, the detection rate would have risen to 54%. Across the region 15% (range 12-20%) of pregnant women were 35 years or more at delivery, and 58% (33-69%) of infants with Down''s syndrome were born to women in this age range.ConclusionsCurrent additional serum or nuchal translucency screening techniques for antenatal detection of Down''s syndrome are less advantageous than previously supposed. More pregnant women were aged over 35 than has been presumed in statistical models used in demonstration projects of serum screening and, as a result, the proportion of affected fetuses in this age group is much greater than predicted.

What is already known on this topic

Serum screening for Down''s syndrome has been presumed to be more effective than screening by maternal ageThere have been no controlled studies comparing serum screening with screening by maternal age, and its greater efficacy has been presumed from mathematical modelling, which assumed that only 5% of pregnant women were aged over 35 yearsThe modelling predicted that only 20-30% of cases of Down''s syndrome would arise in women aged over 35 and made no allowance for the effects of routine anomaly scanning

What this study adds

15% of pregnant women were aged over 35 years, more than double the 5-7% presumed in statistical models of screening58% of babies with Down''s syndrome were born to women aged 35 years or moreSerum screening and nuchal scanning did not achieve significantly higher antenatal detection rates of Down''s syndrome than the use of maternal age and routine anomaly scanning     

Appraisal of a new scheme for prenatal screening for Down's syndrome.

OBJECTIVE--To appraise a new method of prenatal screening for Down''s syndrome based on maternal serum concentrations of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin combined with maternal age--the "triple test." DESIGN--Examination of the cost effectiveness of the triple test relative to screening only by maternal age over a range of population detection rates. SETTING--Leicestershire Health Authority. MAIN OUTCOME MEASURES--Costs per affected fetus detected. RESULTS--The triple test is more cost effective than screening only by maternal age for risk cut off points for amniocentesis, resulting in a detection rate over 45%. The most efficient detection rate is around 60-65%, for which the cost per case detected is around 29,000 pounds, through screening with higher detection rates is still likely to be cost beneficial. CONCLUSIONS--Prenatal screening for Down''s syndrome based on the triple test should replace screening based only on maternal age. Individual women''s preferences should be elicited by the use of structured decision analysis in order to maximise utility and so increase the benefits of the screening programme.     

胎盘特异性基因4 mRNA基因在孕妇外周血中的检测及临床价值

目的:应用实时荧光定量PCR(RT-PCR)技术对不同孕周孕妇外周血浆胎盘特异性基因4(PLAC4)m RNA基因进行检测,寻找唐氏综合征产前诊断的可靠生物学标志物,为无创性产前诊断提供新的突破口。方法:按入组标准随机选取健康育龄未妊娠女性5例,正常健康妊娠孕妇60例(早期妊娠20例、中期妊娠20例、晚期妊娠20例),唐氏筛查高危孕妇8例,正常分娩24 h女性5例。共收集外周血浆样本78例。应用RT-PCR技术,检测样本中的PLAC4 m RNA基因含量,并进行相对定量分析。结果:健康育龄未妊娠女性及正常分娩后24 h女性外周血浆中均无游离胎儿PLAC4 m RNA基因的存在;正常健康妊娠孕妇不同孕周标本均检测到PLAC4 m RNA基因,以早期妊娠作为对照,中期妊娠是早期妊娠的1.99倍,晚期妊娠是早期妊娠的3.73倍;唐氏筛查高危孕妇均检出PLAC4 m RNA基因,含量是早期妊娠的6.36倍。结论:PLAC4 m RNA基因有望成为唐氏综合征产前诊断的可靠性生物学标志物。     

Precision in estimating gestational age and its influence on sensitivity of alphafetoprotein screening.

The interpretation of maternal serum alpha-fetoprotein (AFP) concentrations in relation to fetal neural tube defects depends on accurate assessment of the gestational age. In a quadruple-blind study three antenatal methods of assessment--namely, menstrual dates, clinical examination, and ultrasound scanning--were correlated with postnatal assessment using the Dubowitz scoring system. The best agreement to +/- 1 week was obtained using menstrual dates and ultrasound in combination, such agreement being found in 91 (77%) of the 118 women studied. Since serum AFP concentrations vary with gestational age, precise gestational dating is necessary. In many cases, particularly in women who are unsure of their dates or have irregular menstrual cycles, ultrasound examination is needed to supplement clinical findings.     

Birth weight from pregnancies dated by ultrasonography in a multicultural British population.

OBJECTIVE--To produce standard curves of birth weight according to gestational age validated by ultrasonography in the British population, with particular reference to the effects of ethnic origin. DESIGN--Retrospective analysis of computerised obstetric database. SETTING--Three large maternity units associated with Nottingham University with over 16,000 deliveries a year. PATIENTS--41,718 women with ultrasound dated singleton pregnancies and delivery between 168 and 300 days'' gestation. MAIN OUTCOME MEASURES--Length of gestation, ethnic origin, parity, maternal height and weight at booking, smoking during pregnancy; the effect of these variables on birth weight. RESULTS--Birth weights from ultrasound dated pregnancies have a higher population mean and show less flattening of the birthweight curve at term than those of pregnancies dated from menstrual history. Significant differences were observed in mean birth weights of babies of mothers of European origin (3357 g), of Afro-Caribbean origin (3173 g), and from the Indian subcontinent (3096 g). There were also significant interethnic differences in length of gestation, parity, maternal height, booking weight, and smoking habit which affected birth weight. The ethnic differences in birth weight were even greater when the effect of smoking was excluded. CONCLUSIONS--Birthweight standards require precise dating of pregnancy and should describe the population from which they were derived. In a heterogeneous maternity population the accurate assessment of an individual baby''s weight needs to take the factors which affect birthweight standards into consideration.     

Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

Background

Prenatal screening for Down''s syndrome is performed using biochemical and ultrasound markers measured in early pregnancy such as the Integrated test using first and second trimester markers. Recently, DNA sequencing methods have been introduced on free DNA in maternal plasma, yielding a high screening performance. These methods are expensive and there is a test failure rate. We determined the screening performance of merging the Integrated test with the newer DNA techniques in a protocol that substantially reduces the cost compared with universal DNA testing and still achieves high screening performance with no test failures.

Methods

Published data were used to model screening performance of a protocol in which all women receive the first stage of the Integrated test at about 11 weeks of pregnancy. On the basis of this higher risk women have reflex DNA testing and lower risk women as well as those with a failed DNA test complete the Integrated test at about 15 weeks.

Results

The overall detection rate was 95% with a 0.1% false-positive rate if 20% of women were selected to receive DNA testing. If all women had DNA testing the detection rate would be 3 to 4 percentage points higher with a false-positive rate 30 times greater if women with failed tests were treated as positive and offered a diagnostic amniocentesis, or 3 times greater if they had a second trimester screening test (Quadruple test) and treated as positive only if this were positive. The cost per women screened would be about one-fifth, compared with universal DNA testing, if the DNA test were 20 times the cost of the Integrated test.

Conclusion

The proposed screening protocol achieves a high screening performance without programme test failures and at a substantially lower cost than offering all women DNA testing.     

Serum screening for Down's syndrome: experiences of obstetricians in England and Wales.

OBJECTIVES--To assess the experiences of obstetricians in England and Wales of serum screening for Down''s syndrome. DESIGN--Postal questionnaire survey. SUBJECTS--Questionnaires were sent to all practising obstetricians in England and Wales with nonacademic appointments who had not participated in an earlier (randomly sampled) survey of obstetricians'' attitudes (n = 555). Responses were received from 393 (71%), of which 351 were analysed. The data represent about one third of obstetric consultants in England and Wales. MAIN OUTCOME MEASURES--The extent of use of serum screening for Down''s syndrome, and the problems encountered. RESULTS--Serum screening for Down''s syndrome was being offered on some basis by virtually all obstetricians in the survey. Nearly half the sample said that they did not have adequate resources for counselling all the women to whom screening was offered. Many problems were reported, which in all cases were more common than equivalent problems encountered with serum screening for neural tube defects. Over 80% (289) said that women not understanding the test was a problem. CONCLUSIONS--There is considerable confusion associated with serum screening for Down''s syndrome. The precedent of serum screening for neural tube defects does not seem to have lessened the problems experienced, rather the contrary. Many obstetricians report inadequate resources for counselling, which is consistent with the high prevalence of problems associated with women not understanding the test. There is an urgent need to consider what counselling should consist of and who should undertake it and to ensure that necessary resources are available.     

Screening for small for dates fetuses: a controlled trial.

In the hope of reducing perinatal risks associated with retardation of intrauterine growth a previously described two stage ultrasound screening schedule was evaluated by a controlled trial in 877 women with low risk single pregnancies. The two stages of ultrasound examination were an assessment of gestational age during early pregnancy followed by measurement of length from crown to rump and area of trunk at between 34 and 36 weeks'' gestation. The product of crown to rump length and trunk area was calculated. The sensitivity of this schedule in identifying in advance 94% of babies who were small for dates at birth, with 90% specificity, and the speed and simplicity of measurement confirmed the accuracy and feasibility of two stage ultrasonography as a screening procedure. The controlled trial did not, however, show any benefit from its routine application in these low risk pregnancies.     

Screening for Down's syndrome using serum alpha fetoprotein: a retrospective study indicating caution.

A report was made on the outcome of a four year retrospective study in 27 064 pregnancies, of the clinical efficiency, sensitivity, and specificity of a screening programme for Down''s syndrome based on reported strategies related to the measurement of maternal serum alpha fetoprotein. This study identified 27 pregnancies affected by Down''s syndrome with a median multiple of the median maternal serum alpha fetoprotein concentration of 0.82. This figure is considerably higher than that obtained from previous reports on this subject. With an age related multiple of the median maternal serum alpha fetoprotein strategy, 30.8% of Down''s affected pregnancies were identified as well as 11.6% of unaffected pregnancies. Perhaps a United Kingdom collaborative study should begin to investigate the reasons for such wide population variance in the reports for the median multiple of the median for Down''s affected pregnancies. Until such studies are carried out, screening for Down''s syndrome based on low maternal serum alpha fetoprotein concentration is premature.     

Prenatal and postnatal prevalence of Turner's syndrome: a registry study.

OBJECTIVE--To study prevalence of Turner''s syndrome in Denmark and to assess validity of prenatal diagnosis. DESIGN--Study of data on prenatal and postnatal Turner''s syndrome in Danish Cytogenetic Central Register. SUBJECTS--All registered Turner''s syndrome karyotypes (100 prenatal cases and 215 postnatal cases) during 1970-93. MAIN OUTCOME MEASURES--Prevalence of Turner''s syndrome karyotypes among prenatally tested fetuses and Turner''s syndrome among liveborn infants. RESULTS--Among infant girls, prevalence of Turner''s syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner''s syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner''s syndrome, pregnancy was allowed to continue and 24 children were live born. Thirteen of these children were karyotyped postnatally, and diagnosis of Turner''s syndrome had to be revised for eight, seven being normal girls and one boy. This gives tentative predictive value of amniocentesis in diagnosing Turner''s syndrome of between 21% and 67%. There was no significant relation between mother''s age and risk of Turner''s syndrome. CONCLUSIONS--Discrepancy between prenatal and postnatal prevalence of Turner''s syndrome challenges specificity of prenatal examination in diagnosing Turner''s syndrome.     

Cost-effectiveness analysis for triple markers serum screening for Down's syndrome in Thai setting

BACKGROUND:

Down''s syndrome is an important congenital chromosomal disorder that can be seen around the world. The antenatal screening for this disorder is an important processing in present obstetrics.

OBJECTIVE:

Due to the concept of first do no harm, the use of noninvasive test is recommended. The triple marker screening test has been introduced for a few years and acceptable for its efficacy.

RESULT:

However, an important concern is on its cost-effectiveness. Here, the author analyze and present the cost-effectiveness of the triple markers serum screening for Down''s syndrome in Thai setting.

CONCLUSION:

According to this work, the cost per effectiveness of triple markers serum screening is slightly lower than standard amniocentesis test.     

Results of first year (1989) of a national register of Down's syndrome in England and Wales.

OBJECTIVE--To examine the feasibility of a national register of Down''s syndrome and its effectiveness in evaluating prenatal screening for the syndrome. DESIGN--Information for the register was obtained from all eligible cytogenetic laboratories on relevant cytogenetic diagnoses, including date and place of birth or termination, maternal age, indication for karyotyping, and type of diagnostic test used. SETTING--Cytogenetic laboratories in England and Wales. SUBJECTS--All fetuses with trisomy 21 diagnosed prenatally and live births with Down''s syndrome diagnosed at birth. MAIN OUTCOME MEASURES--Number of prenatal and postnatal diagnoses of Down''s syndrome. National and maternal age specific prevalence of Down''s syndrome. RESULTS--For 1989 there were 1060 registrations--323 prenatal diagnoses and 737 postnatal diagnoses--after exclusion of postnatally diagnosed miscarriages and stillbirths. The estimated national rate of affected births for mothers resident in England and Wales was 1.4/1000 live births, assuming no terminations of affected pregnancies and after correction for natural losses which would have occurred in the absence of termination. The corrected maternal age specific rates were close to those found in previous population based studies. The proportion of affected pregnancies diagnosed prenatally in mothers aged 35 to 39 was 44%, and for those aged 40 or more it was 71%. Abnormal findings on ultrasonography played an unexpectedly important part in initiating cytogenetic investigation (13% of the prenatal diagnoses). CONCLUSIONS--The findings establish the feasibility of a national Down''s syndrome register and its use in evaluating prenatal screening services. Together with information held by the Office of Population Censuses and Surveys on congenital malformations, data from the register will permit studies of environmental variables affecting the prevalence of the syndrome.     

Periodic health examination, 1996 update: 1. Prenatal screening for and diagnosis of Down syndrome. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To make recommendations to physicians providing prenatal care on (1) whether prenatal screening for and diagnosis of Down syndrome (DS) is advisable and (2) alternative screening and diagnosis manoeuvres. OPTIONS: "Triple-marker" screening of maternal serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol; fetal ultrasonographic examination; amniocentesis; and chorionic villus sampling (CVS). OUTCOMES: Accuracy of detection of DS in fetuses, and risks to the mother, including psychologic distress, and to the fetus from the screening and diagnostic interventions. EVIDENCE: A MEDLINE search for relevant articles published from Jan. 1, 1966, to Mar. 31, 1994, with the use of MeSH terms "Down syndrome," "prenatal diagnosis," "screening," "prevention," "amniocentesis," "chorionic villus sampling," "ultrasonography," "anxiety," "depression" and "psychological stress" and a manual search of bibliographies, recent issues of key journals and Current Contents. VALUES: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examination were used. A high value was placed on providing pregnant women with the opportunity to determine whether they are carrying a fetus with DS and to make choices concerning the termination of the pregnancy. The economic issues involved are complex and were not considered. BENEFITS, HARMS AND COSTS: Triple-marker screening identifies an estimated 58% of fetuses with DS, but it has an estimated rate of true-positive results of 0.1% and of false-positive results of 3.7% (given a risk cut-off of one chance in 190 of DS). These rates vary with maternal age and the risk cut-off chosen. Women with a known risk of having a fetus with DS (e.g., those who have had a previous child with DS) may benefit from a reduction in anxiety after confirmation that their fetus does not have DS. Screening allows women at low risk of having a child with DS to detect fetuses with the syndrome, but may cause psychologic distress if there is a false-positive screening test result. Up to 20% of women with positive results of screening tests may decline to undergo a subsequent amniocentesis. Amniocentesis and CVS are very accurate in diagnosing DS in fetuses and have a very low rate of serious complications for the mother. Amniocentesis is associated with a 1.7% rate of fetal loss when it is performed after 16 weeks'' gestation, whereas the rate among controls is 0.7% (for a difference of 1%, 95% confidence interval 0.3% to 1.5%). CVS entails a greater risk of fetal loss than amniocentesis (odds ratio 1.32, 95% confidence interval 1.11 to 1.57). There is little evidence from controlled trials of significant associations between amniocentesis or CVS and neonatal morbidity or malformations; however, samples have been too small to show differences in rare outcomes. Results from some case-control studies suggest that CVS increases the risk of transverse limb deficiency. Costs were not considered because they are beyond the scope of this review. RECOMMENDATIONS: There is fair evidence to offer triple-marker screening through a comprehensive program to pregnant women under 35 years of age (grade B recommendation). Women given detailed information about serum-marker screening show more satisfaction with the screening than those not given this information. There is fair evidence to offer amniocentesis or CVS to pregnant women 35 years of age and older and to women with a history of a fetus with DS or of a chromosome 21 anomaly (grade B recommendation). Information on the limitations and advantages of each procedure should be offered. Triple-marker screening may be offered as an alternative to CVS or amniocentesis to pregnant women over 35. VALIDATION: Recommendations concerning prenatal diagnosis are similar to those of the US Preventive Services Task Force, the Society of Obstetricians and Gynaecologists of Canada, the Canadian College of Medical Geneticists and the Cochrane Pregnancy and Childbirth Group. No previous specific recommendations concerning triple-maker screening exist. SPONSORS: These guidelines were developed and endorsed by the Canadian Task Force on the Periodic Health Examination, which is funded by Health Canada and the National Health Research and Development Program.     

Contribution of ultrasonographic examination to the prenatal detection of trisomy 21: experience from 19 European registers

The objective of this study was to evaluate the contribution of ultrasound scanning to the prenatal detection of trisomy 21 in a large unselected European population. Data from 19 congenital malformation registers in 11 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient. Routine serum screening was offered in four of the 11 countries and routine screening on the basis of maternal age amniocentesis in all. The results show that overall 53% of cases of trisomy 21 were detected prenatally with a range from 3% in Lithuania to 88% in Paris. Ninety-eight percent of women whose babies were diagnosed before 24 weeks gestation chose to terminate the pregnancy. Centres/countries that offer serum screening do not have a significantly higher detection rate of trisomy 21 when compared to those that offer maternal age amniocentesis and anomaly scanning only. Fifty percent of trisomy 21 cases were born to women aged 35 years or more. In conclusions, second trimester ultrasound plays an important role in the prenatal diagnosis of trisomy 21. Of those cases prenatally diagnosed, 64% of cases in women <35 years and 36% of those in women >or=35 years were detected because of an ultrasound finding. Ultrasound soft markers accounted for 84% of the scan diagnoses. There is evidence of increasing maternal age across Europe with 50% of cases of trisomy 21 born to women aged 35 years or more.