Maternal serum alpha-fetoprotein and dimeric inhibin A detect aneuploidies other than Down syndrome

OBJECTIVE: Our purpose was to determine whether the combination of maternal serum alpha-fetoprotein, free human chorionic gonadotropin-beta, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. STUDY DESIGN: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 +/- 5.6 years). Alpha-fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-beta and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. RESULTS: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of alpha-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner's syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). CONCLUSIONS: The combination of maternal serum alpha-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination.     

A new screening protocol combining urine beta-core fragment and ultrasonography for Down syndrome detection

OBJECTIVE: Our purpose was to ascertain the screening efficiency of a new midtrimester Down syndrome detection protocol that combines maternal urine testing and ultrasonographic examination. STUDY DESIGN: In a prospective study, beta-core fragment, the stable end product of human chorionic gonadotropin metabolism, was measured in maternal urine. The results were standardized for urine creatinine levels. The study was performed in women undergoing midtrimester genetic amniocentesis (15 to 24 weeks' gestation). Urine beta-core fragment values were expressed as multiples of the normal median for gestational age. The screening performance of a combination of ultrasonographic parameters and urine beta-core values for Down syndrome detection was determined. RESULTS: A total of 511 singleton pregnancies in women undergoing amniocentesis were studied, 18 of the women (3.5%) had a Down syndrome fetus. A urine beta-core fragment level > or = 97th percentile had a sensitivity of 61.1% and a false-positive rate of 3.2%. An abnormal prenatal screen was defined as a urine beta-core level > or = 97th percentile, increased nuchal thickness (> or = 5 mm), or the presence of gross structural defects. Corresponding values for the screening efficiency of an abnormal prenatal screen were sensitivity of 77.8% and a false-positive rate of 4.1%. With an abnormal prenatal screen the odds ratio is 82.8 (95% confidence interval 22.6 to 364.9) for having a Down syndrome fetus. CONCLUSION: The presence of an abnormal maternal urine beta-core level, a gross ultrasonographic anomaly, or increased nuchal thickness had a high detection rate and a low false-positive rate for Down syndrome. This novel screening algorithm is useful for further delineating the risk status in patients at high risk who are reluctant to undergo or decline genetic amniocentesis.     

Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of hydrocephalic patients

OBJECTIVE: The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection. STUDY DESIGN: With use of commercially available assay kits, medians for free beta-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome. RESULTS: The mean maternal age of the study population was 35.6 +/- 5.3 years. The best three-analyte combination was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher false-positive rate (18%) maternal serum alpha-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases. CONCLUSIONS: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum alpha-fetoprotein, free beta-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectively.     

Comparison of 12 assays for detecting hCG and related molecules in urine samples from Down syndrome pregnancies

Urine is a new medium for Down syndrome testing. In an effort to determine the best type of human chorionic gonadotropin (hCG)-related immunoassay for urine testing, we examined 14 Down syndrome and 91 unaffected pregnancy urine samples with 12 established assays. The assays included (a) those that detect hCG beta-core fragment only; (b) those that detect beta-core fragment with less than 18 per cent free beta-subunit cross-reactivity; (c) that which equally detects free beta-subunit and beta-core fragment; and (d) those that detect hCG, free beta-subunit, or combinations thereof. The seven type a and b assays had the highest sensitivity for Down syndrome. The median MOM for Down syndrome was 5.93 (range 4.73-7.53). At a 10 per cent false-positive rate, the median observed detection rate was 93 per cent (range 79-100 per cent) and the median predicted detection rate was 85 per cent (range 69-96 per cent). The assays that did not mainly detect beta-core fragment (types c and d) had poorer screening performance. The median MOM for Down syndrome was 2.70 (range 2.16-3.63 MOM). At a 10 per cent false-positive rate, the median observed detection rate was 50 per cent (range 36-64 per cent) and the median predicted detection rate was 37 per cent (range 21-62 per cent). We infer that the assays that only detect beta-core fragment, or beta-core fragment with minor free beta-subunit cross-reactivity (types a and b), are the better urine-based tests for Down syndrome screening.     

An alternative for women initially declining genetic amniocentesis: individual Down syndrome odds on the basis of maternal age and multiple ultrasonographic markers

OBJECTIVE: Our purpose was to develop a method of calculating the individual odds of Down syndrome on the basis of a combination of maternal age and multiple ultrasonographic parameters that can be used to counsel women at high risk who initially decline amniocentesis. STUDY DESIGN: Maternal age and ultrasonographic biometry data were collected prospectively on 3254 normal and 30 Down syndrome singleton fetuses between 15 and 24 weeks' gestation. Humerus length data were expressed as multiples of the normal median. Log transformation of the humerus length data permitted their expression in gaussian frequency distributions and the calculation of likelihood ratios for Down syndrome on the basis of humerus length. We also developed likelihood ratios on the basis of the degree of nuchal skinfold thickening and the presence or absence of hyperechoic fetal bowel and hypoplastic fifth digit. RESULTS: The ultrasonographic parameters and maternal age did not significantly correlate with each other and were significant independent predictors of Down syndrome. We therefore calculated the individual odds of Down syndrome by using the product of the age-related risk and the likelihood ratios associated with nuchal thickening, humerus length shortening, and the presence or absence of hyperechoic fetal bowel or fifth digit hypoplasia, respectively. At a Down syndrome risk level of >1:50, a 60.0% detection rate with 4.5% false-positive rate was observed with a screen-positive rate of 5.5%, positive predictive value of 1:10, and odds ratio (95% confidence interval) of 28.4 (12.8 to 64.0). CONCLUSION: This is the first report of individual odds calculation based on multiple midtrimester biometry parameters and maternal age. The screening efficiency is similar to that reported with triple-analyte serum screening. These data are useful for counseling women who are at increased Down syndrome risk and initially decline amniocentesis.     

Levels of urinary beta-core fragment, total oestriol, and the ratio of the two in second-trimester screening for Down syndrome

Levels of beta-core fragment and total oestriol in second-trimester maternal urine samples were measured in 32 Down syndrome pregnancies and 206 control pregnancies. Beta-core fragment and total oestriol values were corrected for the urinary creatinine level and expressed as multiples of the control medians (MOM). In addition, the ratio of the beta-core fragment level to the total oestriol level, without creatinine correction, was calculated, and expressed as MOM values. The median beta-core fragment, total oestriol, and ratio levels in Down syndrome cases were 5.42, 0.64, and 9.32 MOM, respectively. In the Down syndrome pregnancies, 66 per cent of the beta-core fragment levels were above the 95th centile of control levels, while 22 per cent of the total oestriol levels were below the fifth centile of control levels. In combination with maternal age, measurement of beta-core fragment and total oestriol levels in Down syndrome pregnancy resulted in an 80 per cent detection rate at a 5 per cent false-positive rate. Use of the ratio resulted in a univariate detection rate of 72 per cent. In combination with maternal age, the ratio resulted in a detection rate of 81 per cent at a 5 per cent false-positive rate. Based on this unmatched study, the measurement of a ratio of beta-core fragment to total oestriol levels, without the need for creatinine correction, may be useful in screening for fetal Down syndrome in second-trimester urine.     

The effect of gonadotrophin releasing hormone and follicle stimulating hormone in conjunction with pregnant mare serum gonadotrophin on the superovulatory response in crossbred sheep in India

The effectiveness of triple-marker testing as screening for Down syndrome needs to be evaluated by means of formal meta-analytic techniques. We did a MEDLINE search to identify studies evaluating the detection of Down syndrome by use of the triple-marker test. Reference lists of articles were also checked. Papers published in either English, French, or German from 1966 to November 1996 were eligible for this review. Twenty cohort studies were identified. Results of sensitivities and false-positive rates from different subgroups of the study sample were compared by using summary receiver-operating characteristic curve analysis. Medians of sensitivities and false-positive rates were also estimated. A total of 194,326 patients were included. In women of all ages, the medians for sensitivities were 67, 71, and 73 percent when the cutoffs used were 1:190-200, 1:250-295, and 1:350-380, respectively. The median false-positive rates fluctuated between 4 and 8 percent. For women at or above 35 years old, the medians of sensitivity and false-positive rate were 89 and 25 percent, respectively, when the chosen cutoff was 1:190-200. In patients below 35 years old, the median sensitivity was 57 percent if the cutoff used was 1:250-295. Summary receiver-operating characteristic curves showed that 1:190 was the best cutoff for predicting Down syndrome. The triple-marker testing is an effective screening method of detecting Down syndrome pregnancies. It is less effective in younger than in older age groups and may be offered as an alternative to amniocentesis to pregnant women over 35.     

Combining beta-core fragment and total oestriol measurements to test for Down syndrome pregnancies

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.     

Inclusion of serum marker measurements from a previous pregnancy improves Down syndrome screening performance

A predisposition for high or low levels of serum marker concentrations in second trimester Down syndrome screening reflecting itself in consecutive pregnancies in the same woman has been demonstrated, but hitherto the possible effect of including previous marker results in a current risk evaluation has been considered negligible. Using published data on correlations between the markers AFP, hCG and uE3 in different normal pregnancies in the same women and age-related a priori probabilities we found, that in triple marker screening the inclusion of results from a previous pregnancy in a likelihood ratio based risk calculation could increase the detection rate for women having had an earlier pregnancy from 68.0 per cent to 70.2 per cent at a risk cut-off = 1:250. The screen positive rate for normals for the same population of women, being on average older than the total population, fell from 7.1 per cent to 6.8 per cent. These figures, that are based on an assumption of the same correlations between one normal and one Down syndrome pregnancy as between two normal pregnancies, corresponds to an expected reduction, in the population considered, of the number of children born with Down syndrome of 6.7 per cent and of the number of screen positive normals of 4.7 per cent. Considering that this can be achieved at no extra cost, it is concluded that implementation of a procedure for taking information from previous pregnancies into account in second trimester screening should be considered at centres that can handle the software problems involved in doing so. However, better data on the correlations between a normal and a subsequent Down syndrome pregnancy in the same woman should probably be awaited before this is done.     

Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency

The effect of the choice of maternal age-specific prevalence curve on the model predicted Down syndrome detection rate was examined. All 19 published regression curves from 11 birth prevalence series in four meta-analyses were included. The detection rate for a five per cent false-positive rate was estimated for three combinations of markers. For free beta human chorionic gonadotropin and alpha-fetoprotein the lowest predicted detection rate was 62.3 per cent and the highest 64.1 per cent, a range of 1.8 per cent. When unconjugated oestriol was added as a third marker it was 65.6-67.3 per cent, a 1.7 per cent range, and when inhibin A was the fourth marker the detection rate was 72.0-73.4 per cent, a 1.4 per cent range. The number of series included in the regression had the biggest effect: when the authors had used a subset thought to have the highest ascertainment the predicted detection rate generally increased. The type of regression equation used and restrictions on the age range over which the regression was performed were less important factors. The effect of the choice of curve on the predicted increase in detection achieved by incorporating additional markers was relatively small: 3.1-3.3 per cent for unconjugated oestriol and a further 6.1-6.5 per cent for inhibin A. This analysis shows that the model inaccuracy caused by the maternal age curve is not small but is unlikely to be large enough to influence Down syndrome screening policy decisions.     

Evaluation of boys with marked breast development at puberty

OBJECTIVE: The purpose of this study was to investigate the efficiency of second-trimester maternal serum screening for Down's syndrome and open neural tube defects using alpha-fetoprotein and free beta-human chorionic gonadotropin as serum markers. METHODS: 3, 188 women underwent testing between 14th and 22nd week of pregnancy. Of all tested patients, 25.4% were >/=35 years old. A cut-off risk of >/=1:250 for Down's syndrome and MS-AFP >/=2.0 MoM for open neural tube defect were considered screen-positive. RESULTS: The detection rate for Down's syndrome was 77.8% (7/9) with 8.2% screen-positive rate (7.9% false-positive rate). When evaluated separately, in patients younger than 35 and in those >/=35 years old, the screen-positive rates were 3.1 and 23.3%, respectively. A total of 52 (1.6%) were found screen-positive for open neural tube defect; 2 cases of encephalocela and 1 case of gastroschisis were confirmed prenatally. CONCLUSION: The respectable number of cases with trisomy 21 identified in this study confirms that routine mid-trimester screening for Down's syndrome including MS-AFP, free beta-hCG and maternal age is useful in identifying pregnancies at increased risk.     

Effect of allowing for ethnic group in prenatal screening for Down's syndrome

We conducted a study to investigate ethnic group differences in levels of serum markers used in screening for Down's syndrome [serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha- and free beta-hCG, and dimeric inhibin-A], to estimate the extent to which maternal weight differences between ethnic groups explain these differences, and to estimate the effect of adjusting for ethnic group and maternal weight on screening performance. Serum measurements were taken from women who were screened prenatally for Down's syndrome. AFP, uE3, and hCG concentrations were available from 9462 white, 4215 black, and 4392 South Asian women with singleton pregnancies without Down's syndrome or neural tube defects between 15 and 22 weeks' gestational age. Frozen serum samples were available from a subset of 922 white, 449 black, and 135 South Asian women and were used for measurement of free alpha-hCG, free beta-hCG, and inhibin. Values were expressed as multiples of the median (MOM) for women of the same gestational age. There were statistically significant differences in the serum marker levels between ethnic groups that were not explained by differences in maternal weight. The main differences were found in black women compared with white women; black women had serum AFP levels 22 per cent higher (95 per cent confidence interval 20-24 per cent), total hCG levels 19 per cent higher (16-22 per cent), and free beta-hCG levels 12 per cent (3-21 per cent) higher. The other differences were less than 10 per cent. Adjusting for ethnic group only had a small estimated effect on screening performance: a maximum of about 0.5 per cent extra detection at a 5 per cent false-positive rate. At a fixed risk cut-off level, the false-positive rate will not be materially different between different ethnic groups. Adjusting serum markers for ethnic groups improves Down's syndrome screening performance to a very small extent. It is worthwhile because of its established value in AFP screening for open neural tube defects.     

Early transvaginal measurement of transcerebellar diameter in Down syndrome

OBJECTIVE: To evaluate the screening utility of early transvaginal measurement of the transverse cerebellar diameter for identification of Down syndrome fetuses. METHOD: Measurements of the transverse cerebellar diameter were obtained by transvaginal sonography between 11 and 16 weeks of gestation in 544 fetuses with a normal karyotype and in 37 Down syndrome fetuses. RESULTS: The transverse cerebellar diameter was found to show a fairly constant increment of values throughout the period evaluated with a linear relationship to the gestational age. The measurements obtained in Down syndrome fetuses are within the normal range for gestational age. CONCLUSION: The transverse cerebellar diameter cannot be considered a useful tool in the detection of Down syndrome in early pregnancy.     

Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians

PURPOSE: To review information on the benefits of screening with a sensitive thyroid-stimulating hormone (TSH) test for thyroid dysfunction in asymptomatic patients seeking primary care for other reasons. This paper focuses on whether screening should be aimed at detection of subclinical thyroid dysfunction and whether persons with mildly abnormal TSH levels can benefit. DATA SOURCES: A MEDLINE search for studies of screening for thyroid dysfunction and of treatment for complications of subclinical thyroid dysfunction. STUDY SELECTION: Studies of screening with thyroid function tests in the general adult population or in patients seen in the general office setting were selected (n=33). All controlled studies of treatment in patients with subclinical hypothyroidism or subclinical hyperthyroidism were also included (n=23). DATA EXTRACTION: The prevalence of overt and subclinical thyroid dysfunction, the evidence for the efficacy of treatment, and the incidence of complications in defined age and sex groups were extracted from each study. DATA SYNTHESIS: Screening can detect symptomatic but unsuspected overt thyroid dysfunction. The yield is highest for women older than 50 years of age: In this group, 1 in 71 women screened could benefit from relief of symptoms. Evidence of the efficacy of treatment for subclinical thyroid dysfunction is inconclusive. CONCLUSIONS: Even though treatment for subclinical thyroid dysfunction is controversial, office-based screening to detect overt thyroid dysfunction may be indicated in women older than 50 years of age. Large randomized trials are needed to determine the likelihood that treatment will improve quality of life in otherwise healthy patients who have mildly elevated TSH levels.     

Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous testicular tumor

In Japan, a nationwide mass screening system for neonatal metabolic diseases was established in 1977. This system consisted of screening programs for five main congenital metabolic diseases, including phenylketonuria (PKU). To evaluate the efficiency of the mass screening system, a cost-benefit analysis of the screening program for PKU (as a typical case in Japan) was carried out. The costs of the detection and the treatment program were compared with the projected benefit (avoided costs) that results from prevention of the mental retardation associated with the disorders due to PKU. Costs and benefits were discounted at an annual rate of 7%. Assuming that the incidence of PKU was 1/80,500 and the total number of infants screened was 1.2 million, net benefits for the screening program were $283,000, and the cost-benefit ratio was 1:2.5. The sensitivity analysis for the incidence of PKU showed that the cost-benefit ratios exceeded one.     

Normal nuchal thickness in the midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple-screen results

OBJECTIVE: Our purpose was to determine whether nuchal thickness measurement can identify the euploid fetuses in midtrimester pregnancies at increased risk for Down syndrome on the basis of maternal age and serum screening. STUDY DESIGN: Nuchal thickness was obtained prospectively in 651 consecutive fetuses at 14 to 21 weeks' gestation and at > or = 1:270 risk for Down syndrome on the basis of unconjugated estriol, alpha-fetoprotein, and human chorionic gonadotropin levels. The risk of Down syndrome with a normal nuchal thickness was determined. A receiver-operator characteristic curve was used to determine a serum-based risk threshold below which the risk for Down syndrome was low. The prevalence of Down syndrome in fetuses with both a normal nuchal thickness and a below-serum-risk threshold was compared with prevalence in either those above threshold risk or with an abnormal nuchal thickness. RESULTS: There were eight cases of trisomy 21 and one case each of 46,XX/47,XXX, 46,XY/47,XY, +7, and 46,XX, 11q-. The sensitivity of an abnormal nuchal thickness (> or = 6 mm) for detecting Down syndrome was four in eight (50%) (95%) confidence interval 15.3% to 84.6%). The risk of Down syndrome was significantly increased with an abnormal compared with a normal nuchal thickness, four in 13 (30.8%) versus four in 638 (0.6%), p < 0.0001. A risk threshold was defined at > or = 1:100 on the basis of the receiver-operator characteristic plot. Of 390 cases with a normal nuchal thickness and a serum risk estimate < 1:100, there were no cases of Down syndrome (0/390 vs 8/253, p = 0.002). CONCLUSION: Normal nuchal thickness significantly reduces the risk of Down syndrome and may help reduce the number of amniocenteses done for abnormal triple screen results.     

The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy

The objective was to investigate whether cases of fetal trisomy 18 and Turner syndrome with and without hydrops were associated with alterations in the second-trimester levels of maternal serum inhibin A. Twenty-one cases of trisomy 18, 10 cases of Turner syndrome without hydrops and 12 cases of Turner syndrome with hydrops were identified. Five control samples were matched to each case for date of sample collection and completed week of gestation. Inhibin A levels were modestly, but significantly reduced in cases of trisomy 18 (median = 0.88 MoM) and Turner syndrome without hydrops (median = 0.64 MoM). In contrast, inhibin A levels were markedly increased in cases of Turner syndrome with hydrops (median = 3.91 MoM). These data for Turner syndrome are similar to those for human chorionic gonadotropin (hCG). The addition of inhibin A to multiple marker screening (alpha-fetoprotein, unconjugated oestriol and hCG) resulted in a median increase in the Down syndrome risk of 2.6-fold in cases of Turner syndrome with hydrops. The addition of inhibin A to multiple marker Down syndrome screening programmes will be likely to enhance the detection of fetal Turner syndrome with hydrops, but will not contribute substantially to the detection of fetal trisomy 18.     

Recognition memory for novel stimuli: The structural regularity hypothesis.

Early studies of human memory suggest that adherence to a known structural regularity (e.g., orthographic regularity) benefits memory for an otherwise novel stimulus (e.g., G. A. Miller, 1958). However, a more recent study suggests that structural regularity can lead to an increase in false-positive responses on recognition memory tests (B. W. A. Whittlesea & L. D. Williams, 1998). In the present study the authors attempted to identify the circumstances under which structural regularity benefits old-new discrimination and those under which it leads to an increase in false-positive responses. The highly generalizable tendency shown here is for structural regularity to benefit old-new discrimination. The increase in false-positive responses for structurally regular novel items may be limited to situations in which regularity is confounded with similarity to studied items. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The value of screening for Down's syndrome in a socioeconomically deprived area with a high ethnic population

OBJECTIVE: To assess the utility of biochemical antenatal screening for Down's syndrome in a socioeconomically deprived area with a high proportion of Asian women from the Indian Subcontinent. DESIGN: Audit of Down's syndrome biochemical screening service over a four-year period. SETTING: Teaching hospital and community antenatal clinic in inner city Birmingham. POPULATION: Women booked between October 1992 and December 1996. METHODS: Blood for screening was collected between 14 and 21 weeks gestation, alpha-fetoprotein and intact human chorionic gonadotrophin were measured in serum and the risk of Down's syndrome was calculated. MAIN OUTCOME MEASURES: Uptakes of screening and amniocentesis, screen positive rate, odds of being affected given a positive result, miscarriages associated with amniocentesis offered following a high risk result, detection rate, number of Down's cases prevented and a cost analysis. Outcome measures were compared between Asians and Caucasians. RESULTS: Overall 11,974 women (71%) accepted serum screening. The screen positive rate was 8.3% in Asians and 5.0% in Caucasians. The uptake of amniocentesis in women following a high risk result was 54% overall (35% Asian, 67% Caucasian). Nineteen cases of Down's syndrome were identified, of which 13 occurred in women who opted for biochemical screening. The detection rate of the biochemical screening programme was 85% (11/13). Of these 11 cases, six (none of whom were Asian) elected to have an amniocentesis, of whom four thereafter had a termination. CONCLUSION: In this study the public health benefits of screening for Down's syndrome in a socioeconomically deprived area with a high Asian population, were small.     

Taking account of vaginal bleeding in screening for Down's syndrome

OBJECTIVE: To derive a method for revising the risk of Down's syndrome in maternal serum marker screening when there is vaginal bleeding. The effect on screening performance of routinely allowing for the presence or absence of bleeding in all women is also assessed. DESIGN: Overview of published studies on the rate of reported vaginal bleeding in pregnancies with Down's syndrome, on the rate according to maternal age and on the association of bleeding with alpha-fetoprotein (AFP) level. The publications are supplemented with data on unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG) and AFP levels in a consecutive series of screened women. SETTING: Routine Down's syndrome screening tests carried out on women having antenatal care at the St James's University Hospital, Leeds. SUBJECTS: Eight hundred and nine screened women. RESULTS: In five studies the rate of vaginal bleeding in Down's syndrome pregnancies was 1.7 times that in unaffected pregnancies on average. In three studies, the vaginal bleeding rate increased proportionally by 2.2% on average for each year of maternal age. Three studies and our own data were consistent with a 10% increase in the mean AFP level associated with vaginal bleeding, but it did not appear to materially alter uE3 and hCG levels or the standard deviations and correlation coefficients for any of the three analytes. An individual woman's risk was calculated by multiplying her age-specific odds of Down's syndrome by two likelihood ratios, one relating to the vaginal bleeding itself and one from the marker levels. Routine allowance for the presence or absence of vaginal bleeding was estimated to increase the detection rate by less than 1%. CONCLUSION: Our method is of clinical value in revising the risk when there is concern that vaginal bleeding might be responsible for a negative maternal serum Down's syndrome screening result. A policy of routinely incorporating information on vaginal bleeding in risk estimation for all women would have too small an effect on overall screening performance to recommend it.