Prospective evaluation of free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for aneuploidy detection. Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A. Elevated second-trimester dimeric inhibin A levels identify Down syndrome pregnancies. Second-trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome. Multiple screening for fetal Down's syndrome with the classic triple test, dimeric inhibin A and ultrasound. The sensitivity of the trivariate analysis using maternal serum alpha-feto protein, human chorionic gonadotrophin and maternal age in screening for fetal aneuploidy in mothers above the age of 35. Iron status markers in nonanemic pregnant women with and without iron supplementation. Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population. Efficacy of maternal serum screening in the prenatal detection of fetal chromosome abnormalities in Japanese women. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. Maternal serum alpha-fetoprotein screening for chromosomal abnormalities: a prospective study in women aged 35 and older. Screening for fetal Down's syndrome with maternal serum markers--an experience in Italy. Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for Down syndrome. Free beta-hCG subunit versus intact hCG in Down syndrome screening. Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol. Comparison and integration of first trimester fetal nuchal translucency and second trimester maternal serum screening for fetal Down syndrome. The triple-marker test in predicting fetal aneuploidy: a compromise between sensitivity and specificity. Second-trimester maternal serum screening for Down's syndrome: free beta-human chorionic gonadotrophin (HCG) and alpha-fetoprotein, with or without unconjugated oestriol, compared with total HCG, alpha-fetoprotein and unconjugated oestriol. Maternal serum invasive trophoblast antigen (hyperglycosylated hCG) as a screening marker for Down syndrome during the second trimester. A negative second trimester triple test and absence of specific ultrasonographic markers may decrease the need for genetic amniocentesis in advanced maternal age by 60%. Repeat testing of mothers with high human chorionic gonadotrophin levels in Down's syndrome screening. A prospective, double-blind, randomized comparison of prophylactic intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, and intravenous oxytocin, 20 units, for the control of blood loss at elective cesarean section. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. Repeated measurement of pregnancy-associated plasma protein-A (PAPP-A) in Down syndrome screening: a validation study. Comparison of triple-risk assessment of fetal trisomy 21 including total human choriogonadotropin (hCG) or its free beta-subunit (free beta hCG). A randomized trial of prostaglandin E2 gel and extra-amniotic saline infusion with high dose oxytocin for cervical ripening. The outcome of five years' implementation of maternal serum screening for Down's syndrome comparing actual age risks and mode of delivery. Maternal serum screening for down syndrome by using alpha-fetoprotein and human chorionic gonadotropin in an asian population. a prospective study. Combined ultrasound biometry, serum markers and age for Down syndrome risk estimation. Efficiency of ultrasound and biochemical markers for Down's syndrome risk screening. A prospective study. Maternal serum screening for fetal Down's syndrome, a retrospective study. Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study. A randomized trial of oral iron on tests of short-term memory and attention span in young pregnant women. Screening for Down's syndrome and neural tube defect in Croatia. A regional prospective study. Evaluation of a gastric delivery system for iron supplementation in pregnancy. Screening for Down's syndrome in early and late first and second trimester using six maternal serum markers. Elevated maternal urine level of beta-core fragment of human chorionic gonadotropin versus serum triple test in the second-trimester detection of down syndrome. Randomised trial comparing an interactive multimedia decision aid with a leaflet and a video to give information about prenatal screening for Down syndrome. Evaluation of maternal serum alpha-fetoprotein and ultrasound examination to screen fetal chromosomal abnormalities. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Second trimester maternal serum biochemical screening for Down's syndrome: experience of a single obstetric unit. Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay. Use of a decision aid for prenatal testing of fetal abnormalities to improve women's informed decision making: a cluster randomised controlled trial [ISRCTN22532458]. Oxytocin- or low-dose prostaglandin F2 alpha-infusion for stimulation of labor after primary rupture of membranes. A prospective, randomized trial. Comparison of intravenous oxytocin and vaginal prostaglandin E2 gel in women with unripe cervixes and premature rupture of the membranes. Can we decrease postdatism in women with an unfavorable cervix and a negative fetal fibronectin test result at term by serial membrane sweeping? Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation. A prenatal trisomy 21 screening program using alpha-fetoprotein, human chorionic gonadotropin, and free estriol assays on maternal dried blood. A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin. Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis. Risk of fetal Down's syndrome based on maternal age and varying combinations of maternal serum markers. First-trimester or second-trimester screening, or both, for Down's syndrome. Comparison of Down's syndrome screening strategies in Asians combining serum free beta-hCG and alpha-fetoprotein with maternal age.
Our goal was to prospectively evaluate the use of the free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for the detection of fetal Down syndrome and other aneuploidies.
                Women who had a second-trimester multiple-marker screening test (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and genetic amniocentesis from August 1996 to August 1998 were included. Serum was also analyzed for inhibin and the free beta-subunit of human chorionic gonadotropin. Detection and false-positive rates for 4 analyte combinations at 5 different screening risk cutoff points for Down syndrome were determined and compared.
                We evaluated 1256 patients, including 23 with aneuploidy (13 with Down syndrome, 10 others). The maternal age was 35.9 +/- 4.6 years (mean +/- SD). At the optimal risk cutoff point for Down syndrome detection (1:190; false-positive rate, 19%), the multiple-marker screening test plus inhibin was superior, detecting 85% of Down syndrome cases, in comparison with 69% when the multiple-marker screening test alone was used and 62% when the other 2 combinations were used. The multiple-marker screening test plus inhibin also detected 60% of the other aneuploidies.
                When evaluated prospectively in a high-risk population, the multiple-marker screening test plus inhibin was superior to the traditional multiple-marker screening test and 2 other analyte combinations, with a lower false-positive rate and increased detection of all aneuploidies in a high-risk population. To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers.
                A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result.
                For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free beta subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States.
                The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than $31 (ranging from $16 to $39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced.
                The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval. Our purpose was to determine whether second-trimester dimeric inhibin A levels distinguish Down syndrome pregnancies from euploid pregnancies.
                With use of a commercially available enzyme-linked immunosorbent assay (Serotec, Oxford) inhibin A medians were established in stored sera from 40 to 50 euploid pregnancies at each week of gestation from 14 to 20 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels measured in each sample before storage were retrieved. The performance of inhibin A in the multiple-marker screening test was evaluated.
                The mean inhibin A multiple of the median was significantly higher in the Down syndrome group than in the euploid group (2.84 +/- 2.0 vs 1.22 +/- 1.0, p = 0.0001). An inhibin A level > or = 1.6 multiples of the median identified 70% of all Down syndrome pregnancies at a false-positive rate of 22%. Replacing estriol with inhibin A in the multiple-marker screening test resulted in a higher Down syndrome detection rate at a lower screen-positive rate.
                Elevated second-trimester maternal serum inhibin A levels identify Down syndrome pregnancies; replacing estriol with inhibin A in the multiple-marker screening test improves test performance. We measured immunoreactive inhibin in the maternal serum of 80 pregnancies with a chromosomally normal fetus and ten Down's syndrome pregnancies in the second trimester. The inhibin level in all Down's syndrome pregnancies was above the normal median; the multiple of the normal median (MoM) was 1.9. We found a statistically significant difference between the levels of inhibin in unaffected and affected pregnancies (Kolmogorov-Smirnov test: p < 0.002). Using an arbitrarily chosen cut-off of 2.4 MoM, 40 per cent of Down's syndrome and 5 per cent of the normal pregnancies were found. We conclude that immunoreactive inhibin may be useful as a marker for fetal Down's syndrome. The aim of the study was to determine whether inhibin combined with ultrasound improves the classic second trimester triple test. Eighteen Down's syndrome and 200 euploid pregnancies were included. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and estriol (E3), measured between 15 and 20 weeks' gestation by radioimmunoassay, were retrieved. Inhibin A was tested with a specific two-monoclonal-antibody ELISA. Ultrasound was performed between 15 and 25 weeks' gestation: femur length, nuchal thickness and morphological abnormalities were assessed. Statistical analysis used a multivariate discriminant analysis. Except for the classic triple test parameters, only inhibin and the standard deviation score (SDS) for femur length allowed us to make a statistically significant distinction between euploid and Down's syndrome pregnancies. For a 5% false-positive rate, the classic triple test sensitivity was 61%. When E3 was replaced with inhibin A, the sensitivity increased to 77.8% and to 66.7% with SDS femur length. Combining hCG, AFP, SDS femur length and inhibin A gave a sensitivity of 66.7% for a false-positive rate of 2.5%. In conclusion, the classic triple test can be more significantly improved by replacing E3 with inhibin than by including ultrasound. However, a combination of ultrasound and inhibin enhances both the sensitivity and specificity of the test. In Down's syndrome screening, the biological parameters improve sensitivity while ultrasound is a better indication of specificity.
                Copyright 2000 S. Karger AG, Basel This study was undertaken to assess the usefulness of maternal serum human chorionic gonadotrophin, alpha-fetoprotein and maternal age in screening for fetuses with abnormal chromosomes in pregnant women aged 35 years and over. From 1989 to 1991, 1208 women seen at the National University Hospital had karyotyping procedures performed for maternal age > 35 years as well as second trimester serum samples taken for alpha-fetoprotein and human chorionic gonadotrophin. Sixteen (1.3%) chromosomal abnormalities were present. Using cut off risk levels of 1:250 and 1:384, the sensitivity of the analysis in screening for Down's syndrome pregnancies was 71.5% and 86% respectively. For the non Down's chromosomal abnormalities, using cut off risk levels of 1:250 and 1:384, the sensitivity of the analysis was only 22.3% and 33.4% respectively. Thus risk calculations based on the two serum markers and maternal age failed to identify all fetuses with abnormal chromosomes. To measure levels of markers of anemia before and after delivery in women who had high hemoglobin levels during the early stage of the second trimester of pregnancy and did not receive iron supplementation during their pregnancies.
                In a randomized, double-blind, placebo-controlled trial 244 women who had a hemoglobin concentration of 13.2 g/dL or greater and a serum ferritin level higher than 15 microg/L between the 13th and 18th week of pregnancy took either one 150-mg tablet of ferrous sulfate daily or placebo during their pregnancies. Markers of anemia were measured at the time of delivery and 6 weeks postpartum.
                There were statistically significant differences between the 2 groups in hematocrit as well as hemoglobin and ferritin levels both at the time of delivery and 6 weeks postpartum (P<0.05), but these differences were not clinically significant.
                Not using iron supplementation did not cause a considerable decrease in markers of anemia in women with a hemoglobin concentration of 13.2 g/dL or greater in the second trimester of pregnancy. This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin).
                A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis.
                Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed.
                These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result. This prospective study assesses the efficacy of maternal serum screening for use in prenatal diagnosis of fetal anomaly and chromosome imbalance in Japanese women.
                Maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol were measured in 1,055 singleton pregnant women between 14 and 20 weeks of gestation. A calculated risk for trisomy 21 of >/=1/299 or alpha-fetoprotein >/=2.5 multiples of the median was adopted as positive.
                Three hundred and seventy-eight of the 1, 055 women screened (35.8%) were identified as positive. Sensitivity, false-positive rate, and positive predictive value in women aged <35 years were 60.0, 10.6, and 6.8%, respectively, and these values were 87.5, 49.3, and 4.2%, respectively, in women aged >/=35 years. The false-positive rate in women aged <35 years was significantly lower than that for women aged >/=35 years (p < 0.001). Chromosomal abnormalities were identified in 21 cases, including 10 with trisomy 21, 5 with trisomy 18, 2 with trisomy 13, and 4 with other chromosomal disorders. Seventeen of the 21 cases (81.0%) showed screen-positive results, and among these all 10 cases with trisomy 21 were detectable. Two cases with trisomy 18, 1 with trisomy 13 and 1 with isochromosome X showed extremely low human chorionic gonadotropin levels (0.4 +/- 0.1 multiples of the median, mean +/- SE), although they were screen negative. Of the 264 women who did not undergo amniocentesis, none had any clinical findings consistent with aneuploidy after birth.
                Our results suggest that the evaluation of each serum marker, as well as of the calculated risk, was significantly important in the prenatal detection of fetal aneuploidy.
                Copyright 2000 S. Karger AG, Basel. 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.
                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.
                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.
                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. Our purpose was to determine the detection and false-positive rates for maternal serum alpha-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women > or = 35 years old.
                A total of 3896 women had serum maternal serum alpha-fetoprotein levels measured routinely before amniocentesis for the indication of advanced maternal age.
                Eighty-five percent (28/33) of fetal Down syndrome pregnancies had second-trimester risks of > or = 1:270 on the basis of a combination of maternal serum alpha-fetoprotein measurement and maternal age. Risks were also > or = 1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies, translocations, and other nonautosomal chromosome abnormalities in this study population were not associated with altered maternal serum alpha-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of > or = 1:270.
                Maternal serum alpha-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women > or = 35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum alpha-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women. The effectiveness of maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin in screening for Down's syndrome (DS) was evaluated on 840 women who underwent amniocentesis for fetal karyotype on account of their age. The risk of a DS pregnancy was established using the method of Wald et al. (1988b), which combines the age-specific risk with that indicated by the levels of the three serum markers. In women over 35, at cut-off risk levels of 1:250 and 1:380, the false-positive rate was 24 and 34 per cent, respectively. In all nine cases of DS, the estimated risk was higher than 1:250. The best screening strategy with the lowest false-positive rate was obtained by combining the three serum markers. The results suggest that this kind of screening can be proposed during genetic counselling for women under 35 and older women wishing to avoid the risk of miscarriage induced by amniocentesis. To determine the ability of second-trimester maternal serum CA-125 levels to detect fetal Down syndrome.
                From stored, second-trimester maternal serum analyzed previously with the multiple-marker screening test for fetal Down syndrome, we selected 306 samples from euploid pregnancies and 22 samples from Down syndrome pregnancies at 14-20 weeks' gestation. CA-125 levels were measured by enzyme-linked immunosorbent assay and converted to gestational week-specific multiples of the median (MoM).
                The mean maternal age (+/- standard deviation) of the study population was 35.5 +/- 5.3 years. The Down syndrome group CA-125 mean MoM was significantly higher than the euploid group mean MoM (1.47 +/- 0.51 MoM versus 1.05 +/- 0.44 MoM; P < .001). CA-125 at or above 1.5 MoM identified 10 of 22 (45%) Down syndrome cases. Substituting CA-125 for estriol (E3) in the multiple-marker screening test resulted in a lower screen-positive rate (67 of 328, 20% [95% confidence interval {CI} 16, 25] versus 91 of 328, 28% [95% CI 23, 33]) with a similar Down syndrome detection rate (18 of 22, 82%). Alternatively, when the screen-positive rate was held constant, the Down syndrome detection rate improved (20 of 22, 91% [95% CI 71, 99] versus 18 of 22, 82% [95% CI 60, 95]).
                Down syndrome pregnancies have higher second-trimester maternal serum CA-125 levels than euploid pregnancies. CA-125 may be superior to E3 in the multiple-marker screening test for fetal Down syndrome. To assess the ability of second-trimester maternal serum free beta-hCG to detect fetal Down syndrome and to compare free beta-hCG to intact hCG in the multiple-marker screening test for Down syndrome.
                From our bank of stored maternal sera, we selected 40-50 samples from euploid pregnancies at each week of gestation from 14 to 20 weeks and 31 samples from Down syndrome pregnancies. Free beta-hCG was measured by enzyme-linked immunosorbent assay, and week-specific multiples of the median (MoM) were derived. The free beta-hCG Down syndrome detection and false-positive rates were determined. Free beta-hCG was then substituted for intact hCG in the multiple-marker screening test, and the Down syndrome detection and false-positive rates at various risk cutoffs were compared.
                The mean (+/-standard deviation) maternal age of all study samples was 35.6 +/- 5.3 years. The mean Down syndrome free beta-hCG MoM was significantly higher than the mean euploid MoM (2.4 +/- 1.1 versus 1.2 +/- 1.0; P < .001). A free beta-hCG level of at least 1.7 MoM identified 68% of Down syndrome pregnancies at a false-positive rate of 20%. When intact hCG was replaced with free beta-hCG in the multiple-marker screening test, a higher Down syndrome detection rate was achieved at a lower false-positive rate at each of several screen positive risk cutoffs.
                Elevated free beta-hCG levels identify Down syndrome pregnancies. Replacing intact hCG with free beta-hCG in the multiple-marker screening test results in a higher Down syndrome detection rate at a lower false-positive rate. A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio.(ABSTRACT TRUNCATED AT 250 WORDS) It is uncertain whether first trimester nuchal translucency (NT) is more effective than the well-established second trimester serum screening for fetal Down syndrome or whether their combination works best. We report data from a large multicentre non-interventional trial in which all subjects underwent both first and second trimester screening.
                All women who attended the obstetric clinic before 15 weeks' gestation were recruited. An ultrasound examination was performed at 10 to 14 weeks to measure the NT. The nuchal measurements were not acted upon unless the fetus showed gross features of hydrops fetalis. All women had serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG) assay at 15 to 20 weeks. The Down syndrome risk assigned by serum screening was disclosed and amniocentesis was offered if this assigned risk was >or=1:250 or if the women were 35 years and older. The efficacy of different combinations of screening markers was compared.
                Between January 1997 and August 2000, 17 590 women were recruited (19% >or=35 years old). After excluding subjects who miscarried, defaulted the serum test and other reasons, 16 237 pregnancies were analysed. Of these, 35 pregnancies were affected by Down syndrome (2.2 cases per 1000 pregnancies). At a false-positive rate of 5%, the detection rate of Down syndrome by NT alone, NT and age, serum hCG, AFP and age, and NT, hCG, AFP and age were 61%, 69%, 73% and 86%, respectively.
                Integration of NT and second trimester serum AFP and hCG assay yielded the best screening efficacy for Down syndrome.
                Copyright 2002 John Wiley & Sons, Ltd. to review the contribution of unconjugated estriol in Down's syndrome detection, and influence of maternal age, cut-off choice, and population specificity on the balance between triple-marker test sensitivity and specificity.
                Prenatal karyotyping was performed in 2833 pregnant women, 73% of them over the age of 34. Duration of gestation was determined by ultrasound in 98% of women. Prior to amniocentesis, the serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol were evaluated and corrected for weight. The risk of trisomy 21 was calculated for the first 986 subjects using default medians, and for 1847 by our population-specific medians. The cut-off was initially 1:300 at term, but the 1:100 and 1:200 risks were also tested. Down syndrome risk was calculated with alpha-fetoprotein and human chorionic gonadotropin combination as well. Linear logistic regression model was performed to test the ability of aneuploidy markers to classify patients into normal and trisomic groups.
                There were twelve cases of Down's syndrome, seven of trisomy 18, four of trisomy 13, and one trisomy 22. Four cases of aneuploidy (16.7%) referred to women younger than 35. With the cut-off risk of 1:300, detection rate was 87.5% and specificity 63.3%, and with 1:100, 66.7% and 79.5%, respectively. The sensitivity for Down's syndrome was from 75% for cut-off=1:100 to 92% for cut-off=1:300, while detection of other trisomies was less successful (58% and 83%, respectively). Exclusion of unconjugated estriol MoM from the risk calculations reduced detection rate by 33% and improved specificity by 4% independently of cut-off choice. Linear logistic regression analysis showed that only unconjugated estriol was able to correctly classify patients between normal and trisomy 21 (p=0.011, odds ratio=1.445), and normal and trisomy 18 (p=0.0023, odds ratio=1.96) groups.
                The unconjugated estriol significantly contributes in Down's syndrome detection with cost of slightly reduced specificity. The 1:300 risk caused an unfavorable compromise between sensitivity and specificity. A higher cut-off, 1:100, would indicate performance of amniocentesis in women aged 39 years and older, and in those aged 35-39 only after the screen-positive result. The aim of our study was to compare three protocols for second-trimester maternal serum screening for Down's syndrome in the same serum samples, using two triple tests [total human chorionic gonadotrophin (HCG), alpha-fetoprotein, unconjugated oestriol; and free beta-HCG, alpha-fetoprotein, unconjugated oestriol] and a double test (free beta-HCG and alpha-fetoprotein). The three protocols were compared in a series of 23 serum samples from Down's syndrome pregnancies and in a cohort of 2516 pregnant women receiving routine antenatal care between June 1992 and June 1993. Among the 23 affected cases, at a cut-off risk of 1:380, the detection rate of Down's syndrome was comparable with the double test (74%; 17/23) and the triple tests (65%; 15/23) (not significantly different). At the same cut-off risk, in the cohort of 2516 pregnant women screened between 15 and 18 weeks gestation, both protocols using free beta-HCG achieved a significant reduction of the number of false positive cases (P = 0.013 and 0.004 for double and triple tests respectively). We conclude that, compared to total HCG, alpha-fetoprotein and unconjugated oestriol, use of free beta-HCG and alpha-fetoprotein represents a better second-trimester screening test for Down's syndrome, because it significantly decreases the false positive rate at a lower running cost. The addition of unconjugated oestriol to the double test adds no further advantage. Approximately two million pregnancies in the United States are screened for Down syndrome annually by use of second-trimester maternal serum markers. At present, a combination of four markers can identify 75% of affected pregnancies when 5% of screened women are classified as candidates for amniocentesis. Although not currently included in screening panels, invasive trophoblast antigen (ITA) is a promising screening marker in serum or urine in both the second and first trimesters. This study aims at better defining the screening performance of serum ITA in the second trimester.
                In an earlier study, serum samples from an unbiased sampling of 45 Down syndrome (cases) and 238 unaffected (control) pregnancies between 14 and 20 weeks of gestation were collected from various centers in the United States. Samples were aliquoted and stored at -20 degrees C for 8 years. We measured ITA in these samples and determined the screening performance both univariately and in combination with other screening markers.
                The median ITA in Down syndrome pregnancies was >3.00 multiples of the median, higher than that found for human chorionic gonadotropin (hCG) or free beta-hCG. At a 5% false-positive rate, ITA univariately detected 38% and 40% of Down syndrome pregnancies, respectively, when assigned by date of last menstrual period or ultrasound date. Modeling yielded rates of 45% and 48%. ITA correlated strongly with hCG and free beta-hCG. When substituted for either of these in a multiple marker panel, ITA performed comparably.
                This study indicates that serum ITA is an effective marker for Down syndrome. It is highly correlated with both hCG and free beta-hCG and could replace either of them in a multiple marker panel. A study was conducted to evaluate the sensitivity of combining a second trimester triple test and targeted ultrasound in order to detect Down syndrome in women undergoing amniocentesis over 35 years of age.
                Women over 35 years of age underwent a triple test and an ultrasound examination for chromosomal markers immediately prior to genetic amniocentesis.
                One thousand and six women were examined. Four hundred and thirty seven were triple test-positive and in 195 cases ultrasonographic abnormalities were observed. Thirteen had Down syndrome and eight had other chromosomal abnormalities. All women with Down syndrome babies were triple test-positive and seven also had ultrasonographic markers. Three of eight women who had babies with chromosomal aberrations other then Down syndrome were also triple test-positive.
                The use of the triple test as a screening tool in our population would reduce the number of amniocenteses by 60%, while no cases of Down syndrome would be missed. Ultrasonographic markers have added little to this population. Three non-Down syndrome chromosomal abnormalities and two Down syndrome mosaic cases would be missed by this approach.
                Copyright 2002 John Wiley & Sons, Ltd. Multiples of medians of serum markers are assumed to be independent of gestational age: every algorithm used for Down's syndrome risk evaluation is based on this hypothesis. However, our former observations suggested that multiples of medians of human chorionic gonadotrophin in Down's syndrome are dependent on gestatational age. Furthermore, observations on 84 Down's syndrome cases confirmed that human chorionic gonadotrophin multiples of medians in samples drawn at 15-17 weeks are approximately 10% lower than in samples drawn at 18-21 weeks, thus showing that the human chorionic gonadotrophin concentration decreases about 10% less than expected. The control group comprised 554 women with two blood samples and normal human chorionic gonadotrophin at first sampling. A further group of 532 women with multiples of medians at first sampling > 1.8 was examined with the aim of excluding an association between the human chorionic gonadotrophin trend in Down's syndrome and high starting values. The trend is peculiar to human chorionic gonadotrophin in Down's syndrome pregnancies and may help to explain the increase in detection rate with gestational age. Based on these findings, screening can be optimized, thus improving performance. Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section.
                A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests.
                The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation.
                Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section. To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis.
                Randomised clinical trial.
                University hospital.
                All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001.
                Enrolled women were randomly assigned oral S-adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery.
                Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant.
                Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups.
                In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus. To confirm that measuring pregnancy-associated plasma protein-A (PAPP-A) in both first- and second-trimester serum samples improves Down syndrome screening.
                We selected paired first- and second-trimester stored serum samples from 34 Down syndrome pregnancies (cases) and 514 unaffected pregnancies (controls) and tested the second-trimester samples for PAPP-A and dimeric inhibin-A (DIA). First-trimester PAPP-A measurements were already available, as were second-trimester measurements of alpha-fetoprotein, unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG).
                PAPP-A was lower among cases than controls (0.47 MoM) in the first trimester (at an average of 12.5 weeks); in the second trimester, it was not different (0.91 MoM). Using repeated measures of PAPP-A alone, 21 of 34 cases were detected (62%, 95%CI 44% to 78%) with 5% false positives. At an observed 2% false-positive rate, the detection rates (DR) for the quadruple (69%) and serum integrated (69%) tests were lower than for the repeated measures test (75%). Modelled performance at 12 weeks was similar to these observed findings (70, 75, and 82%, respectively). If the first-trimester samples were collected at 10 weeks, however, DR would be higher (70, 81, and 91%, respectively).
                Adding a repeated measure of PAPP-A to existing serum markers improves Down syndrome screening to levels that are currently obtainable only by including ultrasound measurement of nuchal translucency (NT). Serum-based screening has the advantages of higher availability and reliability at a lower cost, resulting in a more effective screening strategy. A serum-based repeated measures test has a place in routine Down syndrome screening. Second trimester total hCG and free betahCG levels in maternal serum samples of 33 pregnancies affected by fetal trisomy 21 and of 188 matched controls were compared in a retrospective study. To find out differences of discriminating efficacy by using one of these markers a multivariate discriminant analysis was performed.
                Statistical evaluation was performed for hCG/free betahCG frequency distributions. Discriminant analysis was carried out using the status 'affected' or 'unaffected' as the group variable and the serum markers unconjugated estriol (uE3), alpha-fetoprotein (AFP), and alternatively, hCG or free betahCG, as discriminant variables.
                The median of free betahCG MoM values in affected pregnancies was slightly higher (1.90 MoM) than the median of total hCG MoM values (1.72 MoM) but a lower standard deviation was stated for the logarithmic hCG MoM values (SD = 0.49) compared with free betahCG MoM values (SD = 0.51). A two-tailed Student's t test revealed no significant differences of hCG and free betahCG MoM values in both the affected and unaffected pregnancies. By inclusion of free betahCG the discriminant analysis classified 26 out of 33 affected cases correctly and 45 out of 188 unaffected cases incorrectly. For the inclusion of hCG these ratios were 25/33 and 41/188, respectively. Taking in account the individual maternal age risks at a defined false-positive rate of 5% including free betahCG yielded a higher detection rate than including hCG. However, using 1:380 (age-related at-term risk of a 35-year-old woman) as a cut-off risk including hCG yielded a higher detection rate than including free betahCG.
                For the observed cases none of the markers, hCG or free betahCG, was superior in Down syndrome screening.
                Copyright 2003 S. Karger AG, Basel Our purpose was to compare the efficacy of extra-amniotic saline infusion plus high dose oxytocin with prostaglandin E2 intracervical gel (Dinoprostone) for preinduction cervical ripening.
                166 nulliparous women with term pregnancies, vertex presentation, intact membranes and a Bishop score < or = 4 referred for labor induction were randomly assigned to receive a 0.5 mg PGE2 intracervical gel and extra-amniotic saline infusion (EASI) plus high-dose oxytocin. Changes in the Bishop scores, labor progress, various labor end points and outcomes of labor were assessed. Data were analyzed using chi2 analysis or the Student t-test.
                151 women were studied after 15 exclusions, 75 were assigned to PGE2, and 76 to EASI. The groups were similar in age, race, indication for induction and gestational age. The EASI group had a significant improvement in Bishop score and greater dilation. The mean time to vaginal delivery was 11.4+/-4.8 hours and 18.9+/-6.4 hours for the EASI and PGE2 groups respectively (P=0.001). The cesarean delivery rate was not significantly different between the two groups (25% for the EASI group; 34.6% for the PGE2 group). The cesarean rate due to failure to progress, fetal labor intolerance, and maternal and neonatal outcomes were similar in the two groups.
                Preinduction cervical ripening with EASI plus high dose oxytocin resulted in greater changes in Bishop score, and shorter time to normal vaginal delivery than with PGE2 gel in nulliparous women, without increasing the cesarean rate due to failure to progress or fetal labor intolerance. In this paper 13 613 triple test results from the period 1992- 1997 were analysed. The probability of receiving a high risk result for Down's syndrome from a serum screen, related to the patient's age, was calculated. The modes of delivery of the patients receiving a high risk result were also compared with the rest of the population. The probability of receiving a high risk result increased from 1.2% at 25 years of age to 43.9% at 40 years of age. There was a decrease in the likelihood of having operative intervention at delivery amongst the high risk group but this did not reach statistical significance. This highlights the need for accurate information in risk and probability when counselling a patient undergoing serum screening. Patient's anxiety relating to mode of delivery may also be alleviated by knowing they have no greater risk of operative delivery. The purpose of the present study is to evaluate the efficacy of second-trimester maternal serum screening program by using alpha-fetoprotein (AFP) and total human chorionic gonadotropin (hCG) in an Asian population. During June 1994 to July 1998, we conducted a prospective study of serum screening protocol for Down syndrome. The cut-off point for a positive result in this analysis was a risk of >/=1/270. A total of 17,742 pregnant women with singleton pregnancy were screened, and 1,153 (6.5%) had positive result. Sixteen of the 17,742 pregnancies had Down syndrome, and 10 of them had positive result. The positive rate and detective rate for Down syndrome were 6.5 and 62.5%, respectively. However, the detective rate will reduce to 47.6% after being adjusted by age-specific risk. It is indicated that the double-marker test using AFP and total hCG is an effective screen strategy for second-trimester detection of Down syndrome in Asian women.
                Copyright 2000 S. Karger AG, Basel. To compare Down syndrome screening efficiency of the standard serum triple analyte screen to that of a four-component screen consisting of ultrasound biometry and serum markers in the second trimester.
                The Down syndrome screening efficiency of the triple screen, i.e. alpha-fetoprotein (AFP), unconjugated estriol (E3), hCG and maternal age, was compared with the four-marker algorithm, i.e. humerus length, nuchal thickness, AFP and hCG plus maternal age. A quadrivariate Gaussian algorithm was used to calculate individual Down syndrome odds. Receiver operating characteristic (ROC) curves plotting sensitivity against false-positive rate were constructed for each algorithm and the areas under the curves were compared to determine which was superior. Sensitivity and false-positive rates at different Down syndrome risk thresholds were also compared.
                There were 46 cases of Down syndrome (1.9%) with 2391 normal singleton pregnancies in a referral population in which triple screen, fetal biometry and karyotype had been done. The gestational age range for the study was 14-24 completed weeks. The median maternal age for the study group was 35.0 years (14.0-46.0 years). The areas (SE) under the ROC curves were 0.75(0.04) and 0.93(0.02) for the standard triple and the four-marker screen, respectively (P < 0.001). At a 10% false-positive rate, detection was 45.7% for the triple and 80.4% for the four-marker screen.
                A new algorithm combining humerus length and nuchal thickness measurement with serum AFP, hCG and maternal age substantially improved Down syndrome screening efficiency compared with the traditional triple screen. The model appears promising and should be evaluated in an independent data set. To evaluate the sequential combination of ultrasound screening for fetal aneuploidy at 11-14 weeks with maternal biochemistry at 12-14 and 15-18 weeks of gestation.
                A prospective study including 1,656 women, with a singleton pregnancy booked before 13 weeks of gestation. Nuchal translucency (NT) thickness was measured by transabdominal ultrasound examination. alpha-Fetoprotein, free betahCG and hCG were measured by immunoradiometric (12-14 weeks) or immunometric (15-18 weeks) assays. Derived risks were then calculated. Cutoff risks were chosen first arbitrarily at 1/250 and then adjusted for a 5% false-positive rate.
                Seven fetal aneuploidies were diagnosed, including 5 Down's syndromes, 1 trisomy 18 and 1 triploidy. Three Down's syndromes had concordant high risk with the 3 screenings. One was at low risk with NT, and another was at low risk by maternal serum screening, but sequential combination of screenings led to a 100% detection rate with cutoffs of 1/240, 1/160 and 1/250 for NT, first- and second-trimester biochemistry, respectively (i.e. for a cutoff adjusted for a 5% false-positive rate).
                This preliminary study suggests a benefit in combining maternal age-related risk together with NT and biochemical markers in the first or the second trimester. The algorithm combining these risks needs to be established in a wide population. A retrospective study of the different biochemical markers used in screening for Down's syndrome was carried out on serum from 18,600 women between their 15th and 18th week of pregnancy. Thirty-two sera were from women with fetal Down's syndrome. The retrospective study of these 32 sera involves: (a) the screening of the maternal serum concentrations of human chorionic gonadotropin (hCG) and of alpha-fetoprotein (AFP); (b) the evaluation of the risk of Down's syndrome when screening maternal serum concentrations of hCG alone, then the combination of the two markers and finally the maternal serum concentrations of unconjugated estriol (uE3). The mean of MOM (multiples of the median) for the pathological sera were calculated for hCG (1.91), for AFP (0.63), for the ratio hCG over AFP (3.02) and for uE3 (0.72). With the use of hCG alone we estimated a 41% detection rate for an amniocentesis rate of 5.3%, whereas when hCG was combined with AFP the detection rate approached 65% for an amniocentesis rate of 5.5% at a risk cut-off of 1:300. The results of the uE3 determination confirm the validity of this marker. The comparison of these results with other retrospective studies shows the incidence of different factors in the detection rate such as the choice of markers, the age group studied, the modes of calculating the risk and the actual cut-off chosen. To compare nuchal translucency and second-trimester maternal serum measurements as alternative methods of antenatal screening for Down syndrome in a low-risk population and to evaluate the consequence of combining the results in the estimation of risk.
                In a consecutive series of 4130 women aged less than 38 years with a singleton pregnancy, we examined both the detection rate of Down syndrome by nuchal translucency measurement at 10-14 weeks and maternal serum screening by human chorionic gonadotrophin and alpha-fetoprotein at 14-18 weeks. Women with a nuchal translucency measurement of > or = 3 mm and women with a maternal serum screening-derived risk > or = 1/250 were recommended to have amniocentesis. A second-trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was recorded prospectively and the detection rate and false-positive rate of different screening strategies were retrospectively analyzed.
                Out of the 4130 pregnancies that were followed (mean maternal age, 30.1 years), 12 cases of Down syndrome were observed (0.28%), all detected prenatally. Seven of 12 cases had a nuchal translucency measurement of > or = 3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of > or = 1/250 (60%). Four of the five Down syndrome cases with a nuchal translucency measurement of < 3 mm were detected by subsequent maternal serum screening. At a threshold giving 5% of positive tests, the sensitivity of nuchal translucency, maternal serum screening and combined risk screening were 75%, 60% and 90%, respectively.
                In screening for Down syndrome, an approach which combines the results from first-trimester nuchal translucency and second-trimester biochemistry is effective and increases the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of maternal serum screening-derived risk should be combined with the first-trimester nuchal translucency measurement. Recent studies suggest that infant behavior and psychological test performance are impaired by iron deficiency and may be improved by iron. Comparable studies have not been performed in older populations. Young women early in pregnancy whose nutritional intake may be impaired by poverty constitute a high-risk population. Women aged 14-24 years coming for prenatal care at or before 16 weeks gestation whose hematocrits were greater than or equal to 31% were randomized in a double-blind trial to receive vitamins supplemented with iron (experimental group) or vitamins alone (controls). Hematologic status and tests of short-term memory and attention span were assessed at entry and conclusion of the one-month treatment period. The experimental group showed significant improvement on the most sensitive measure of short-term memory and three subtests. On comparison of the change between initial and final scores, the experimental group showed significant or borderline greater improvement than controls on three tests. These results indicated a beneficial effect of iron therapy on psychometric test-score performance. 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.
                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.
                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.
                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. The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women. The efficiency of six maternal serum markers for Down's syndrome (DS), alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), free beta-hCG, pregnancy-associated plasma protein-A (PAPP-A), the proform of eosinophil major basic protein (ProMBP), pregnancy-specific-beta-1-glycoprotein (SP(1)), and combinations thereof, was examined. Discriminant analysis in 156 DS pregnancies and 546 controls defined three effective combinations of serum marker logMoMs (multiples of the median in control samples) in three gestational age windows, i.e. Index I (weeks 7-9) = 0.52 logMoM ProMBP + 0.28 logMoM PAPP-A - logMoM SP(1); Index II (weeks 10-12) = 1.94 logMoM free beta-hCG - logMoM SP(1), and Index III (weeks 15-19) = 0.78 logMoM free beta-hCG + 1.12 logMoM ProMBP - logMoM AFP. The estimated detection rates of indices and age for a false-positive rate (FPR) of 5% were 73% for Index I, 69% for Index II, and 60% for Index III. Including the ultrasound marker nuchal translucency, using a DS at term risk of 1 : 400 as cut-off, the detection rates of the indices increased to 86, 83, and 82% for FPRs of 4.3, 4.1, and 5.8%, respectively. The indices are promising markers for screening for DS. This study was undertaken to compare the Down syndrome screening efficiency of elevated maternal urine level of the beta-core fragment of human chorionic gonadotropin with that of the traditional serum triple test.
                Urinary beta-core fragment and serum analyte levels were measured prospectively in women with singleton pregnancies who were undergoing second-trimester genetic amniocentesis. Urinary analyte levels were measured within a week of specimen collection. In some cases only alpha-fetoprotein was measured initially and human chorionic gonadotropin and unconjugated estriol levels were subsequently determined from the stored serum specimens. The Down syndrome screening efficiency of urinary concentration of beta-core fragment plus maternal age was compared with that of the traditional triple test. Receiver operating characteristic curves were generated for each algorithm and the areas under the curves were compared to determine which algorithm was superior.
                There were a total of 926 study patients, of whom 21 (2.3%) carried fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses with Down syndrome) had serum alpha-fetoprotein alone measured initially. Urinary concentration of beta-core fragment had a 61.9% detection rate with a 4.9% false-positive rate for Down syndrome, whereas the values for the triple screen were 57. 1% and 11.2%, respectively. The areas under the receiver-operating characteristic curves were 0.8744 for elevated urinary beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the false-positive rate was fixed at an ideal threshold value (</=5%) the urine test was superior (area under the curve, 0.0212 vs 0.0133, P <.05). Similarly, when we considered only cases in which the complete triple screen was performed prospectively (17 fetuses with Down syndrome and 431 fetuses without Down syndrome), the urine test was significantly better (area under the curve, 0.873 vs 0.624, P =.012).
                In this first reported direct comparison we consistently observed higher sensitivity values for screening with urinary levels of beta-core fragment than for serum triple screen, suggesting an equivalent or superior Down syndrome screening performance for the urinary analyte. It is important that freezing and prolonged urine storage before testing be avoided. The reduced cost (single- versus triple-analyte testing) and excellent screening performance support large-scale testing and evaluation of maternal urinary beta-core fragment measurement as an alternative to the traditional serum triple test. (1)To compare an interactive multimedia decision aid (IMDA) with a leaflet and a video to give information about prenatal screening for Down syndrome and (2) to determine the women's acceptance of IMDA.
                Two hundred and one women were recruited from the prenatal clinic of a university teaching hospital and randomised into the intervention group (IMDA, video, and information leaflet) or the control group (video and information leaflet).
                There were no significant differences in the initial decision for and the final uptake of the prenatal screening test between the control and intervention groups. The proportion of women who were undecided was less than 10% in both groups. Of the women in the intervention group, 86.6% and 78.9% agreed that IMDA was user-friendly and acceptable, respectively. Significantly more women aged < 35 (88.1%) accepted IMDA than women aged > or = 35 (68.3%) (P = 0.030), but the logistic regression analysis did not confirm this finding after adjusting for other factors (computer knowledge and usage of computer).
                The use of IMDA did not affect the women's overall uptake rate of the prenatal screening test for Down syndrome. More women less than 35 years accepted IMDA probably because they used computer more frequently and had more computer knowledge.
                Copyright 2004 John Wiley & Sons, Ltd. Maternal serum alpha-fetoprotein (MSAFP), anatomic anomalies and precocious defects of foetal growth were shown as possible "indicators" of foetal chromosomal pathology, in particular Down's syndrome, and thus suggested for prenatal screening of risk patients for this chromosomal abnormalities. The Authors carried out a retrospective study on 1472 patients who underwent amniocentesis for prenatal diagnosis. Between the 15th and the 20th week, a dosage of MSAFP was effected, in order to evaluate if the serum concentration of this substance could predict Down's syndrome. A contemporary study by echographic monitoring was effected on 500 patients from the 1st trimester of pregnancy, in order to detect possible foetal growth retardation precociously and to determine the karyotype in these cases. Results are very interesting and suggest both the dosage of MSAFP and the ecographic monitoring for prenatal screening of trisomy 21, especially in maternal age classes younger than 40 years, where the cost/benefit ratio of screening for maternal age is less favourable. Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP. The objective of this study was to assess the effects of mid-trimester biochemical screening on the prenatal diagnosis of Down's syndrome. All patients booked for antenatal care at the Royal Free Hospital are offered a double marker biochemical screening test (alpha-fetoprotein and free beta human chorionic gonadotrophin). The results of double marker screening tests and the notes of all cases of trisomy 21 from 1 April 1993 to 31 March 1995 were reviewed. Of the 6170 women booked in the antenatal clinic during this 2-year period 4427 (71.8%) took up the offer of biochemical screening. Four hundred and twenty-nine (9.7% of those screened) were reported positive and 293 karyotypes were performed in this group (68.3% uptake) and 253 karyotypes were also performed for other indications. Thirteen of 21 affected pregnancies had biochemical screening. The detection rate of biochemical screening in women aged <37 years was 0% (0/2) with a 8.4% false positive rate. In women aged 37 years the detection rate was 100% (11/11) with a false positive rate of 23%. The overall detection rate for Down's syndrome was 84.6% and the false positive rate was 9.5%. In conclusion, biochemical screening successfully targeted affected pregnancies in women aged 37 years and was useful in reducing the fetal karyotyping rate. However, it was disappointing in the prenatal diagnosis of trisomy 21 in women <37 years old. To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome.
                In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free beta-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population.
                Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free beta-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free beta-hCG was used and some 7% lower than when total hCG was used.
                Maternal serum GlyhCG, as measured by the sialic acid-binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester.
                Copyright 2002 John Wiley & Sons, Ltd. To evaluate the effectiveness of a decision aid for prenatal testing of fetal abnormalities compared with a pamphlet in supporting women's decision making.
                A cluster randomised controlled trial.
                Primary health care.
                Women in early pregnancy consulting a GP.
                GPs were randomised to provide women with either a decision aid or a pamphlet. The decision aid was a 24-page booklet designed using the Ottowa Decision Framework. The pamphlet was an existing resource available in the trial setting.
                Validated scales were used to measure the primary outcomes, informed choice and decisional conflict, and the secondary outcomes, anxiety, depression, attitudes to the pregnancy/fetus and acceptability of the resource. Outcomes were measured at 14 weeks of gestation from questionnaires that women completed and returned by post.
                Women in the intervention group were more likely to make an informed decision 76% (126/165) than those in the control group 65% (107/165) (adjusted OR 2.08; 95% CI 1.14-3.81). A greater proportion of women in the intervention group 88% (147/167) had a 'good' level of knowledge than those in the control group 72% (123/171) (adjusted OR 3.43; 95% CI 1.79-6.58). Mean (SD) decisional conflict scores were low in both groups, decision aid 1.71 (0.49), pamphlet 1.65 (0.55) (adjusted mean difference 0.10; 95% CI -0.02 to 0.22). There was no strong evidence of differences between the trial arms in the measures of psychological or acceptability outcomes.
                A tailored prenatal testing decision aid plays an important role in improving women's knowledge of first and second trimester screening tests and assisting them to make decisions about screening and diagnostic tests that are consistent with their values. One hundred consecutive women with singleton pregnancies and primary rupture of membranes (PROM) after 36 weeks of gestation were included in a prospective, randomized trial of intravenous infusion of oxytocin (up to 30 mIU/min) versus low-dose prostaglandin F2 alpha(PGF2 alpha, up to 6.0 micrograms/min). Cesarean section was performed in 12 patients because of suspected disproportion or intra-uterine asphyxia. Effective contractions or labor progress failed to become established within 8 hours in another 4 women stimulated with PGF2 alpha and 2 stimulated by oxytocin. The stimulation delivery time (hours) for the remaining 82 women treated with PGF2 alpha or oxytocin, respectively was 8.7 against 12.1 for initial Bishop score less than 5 (p less than 0.01), (Mann-Whitney test), 7.2 vs. 7.1 for Bishop score 5-8 and 5.7 vs. 4.2 for Bishop score greater than 8. Patients with initial Bishop score less than 5 seemed to need analgetics less often when treated with PGF2 alpha than with oxytocin. Frequencies of side effects and instrumental deliveries as well as the fetal outcome were similar for the two treatment schedules. The results of the study suggest that low-dose PGF2 alpha infusion may be the more appropriate treatment for women with an unfavorable initial Bishop score. To induce cervical priming and labor, 20 nulliparous term pregnant women with premature rupture of the membranes and unfavorable cervical states were randomly given either oxytocin intravenously or 4 mg prostaglandin E2 in gel intravaginally. One of ten women receiving oxytocin had a favorable cervical state within five hours and vaginal delivery within 24 hours after the start of the infusion compared with six of ten women after prostaglandin E2 gel application. This difference is statistically significant (P less than .01). The number of instrumental deliveries was nine (four cesarean sections and five vacuum extractions) in the oxytocin-treated patients compared with only two vacuum extractions in women who received prostaglandin E2 gel. This difference is also statistically significant (P less than .01, Fischer exact test). In a subsequent open study, 4 mg prostaglandin E2 gel was applied vaginally to 17 term pregnant women of mixed parity with premature rupture of the membranes and unfavorable cervixes. In 12 women a favorable cervical state was achieved within five hours after gel application, and all these women were delivered within 24 hours. None of the women required cesarean section but two required delivery by vacuum extraction. There were no perinatal losses, but two infants in the oxytocin-treated group had Apgar scores less than 7 at five minutes. At pediatric follow-up after two and six months, all infants were normal. In both obstetric and perinatal outcome prostaglandin E2 gel thus seems to be superior to oxytocin for labor induction in term pregnant patients with premature rupture of the membranes and unfavorable cervixes. Our purpose was to determine whether the risk for postdatism can be reduced by serial membrane sweeping in women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result.
                Women with uncomplicated pregnancies, who were candidates for a vaginal delivery with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result were asked to participate in this investigation. Patients were chosen at random and assigned to a group for membrane sweeping every 3 days or to a control group who received gentle examinations every 3 days.
                Sixty-five women were selected at random for serial membrane sweeping (n = 33) or for the control group (n = 32). Although gestational age and Bishop score at study entry were similar, the gestational age on admission for delivery was earlier in the membrane sweeping group (39.9 +/- 0.3) versus the control group (41.5 +/- 0.6, P < .0001). The Bishop score on admission to labor and delivery was greater (8.8 +/- 2.1) in the membrane sweeping group than in the control group (6.2 +/- 2.7, P < .0001). The number of women admitted for labor inductions at 42 weeks' gestation was 18 of 32 (56%) in the control group versus none (0 of 24) in the membrane-sweeping group (P < .0001).
                Women with an unfavorable cervix at 39 weeks' gestation and a negative fetal fibronectin test result are at risk for not being delivered by 41 completed weeks and thus may require postdates induction or antenatal testing. Serial membrane sweeping significantly reduces the risk of postdatism and induction of labor. To compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women.
                Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test.
                Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000).
                Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia. The feasibility of large-scale Down syndrome maternal screening with dried blood samples and nonradioactive methods was examined.
                A prospective observation study was performed on a nonselected population of 11,241 pregnant women sampled between January 1991 and September 1992, between 14 and 24 weeks' gestation (ultrasonographic scanning available for 91.6%), through a multicenter collaborative network. Enzyme-linked immunosorbent assays for alpha-fetoprotein, human chorionic gonadotropin, and free estriol were performed on dried blood samples. Risk determination was made with an in-house software implementing the multivariate gaussian log likelihood method.
                A total of 10,450 samples were eligible for the study. Mean age at term was 27.9 years. A total of 6.84% of the patients were > or = 35 years old with a prior risk of trisomy 21 > 1:350. The general positive rate of our sample was 8.15%. After calculation 31.7% with prior risk > 1:350 were still in the high-risk group; 6.36% of the low-risk group were found to be at high risk for Down syndrome. Fifteen trisomic pregnancies were observed, of which 11 had a calculated risk higher than the selected cutoff value (1:350). The overall detection rate was 73%, specificity was 92%, and positive predictive power was 1.2%.
                Our pilot study has shown performances within the range of conventional serum screening programs. Dried blood assays are a handy alternative to serum assays. Blot paper cards represent a simple method of sampling, well fitted for large population screening. Combined with nonradioactive methods, this method appears to be both low cost and effective. The current work apparently is the first large-scale Down screening program performed with dried blood. This study was conducted to determine if lower dose heparin (LD Heparin) combined with aspirin is as efficacious as higher dose heparin (HD Heparin) for the treatment of the antiphospholipid antibody syndrome in women seeking pregnancy. The method of the study was a prospective, single center trial including 50 patients who were consecutively assigned to treatment. Each patient had at least three consecutive, spontaneous pregnancy losses, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Data were compared using Fisher's exact test. Viable infants were delivered from 20/25 (80%) women treated with higher dose heparin vs. 19/25 (76%) of women treated with lower dose heparin. There were no significant differences between groups with respect to gestational age at the time of delivery (37.2 +/- 3.4 versus 37.7 +/- 1.6 weeks), maternal complications, or fetal complications. A lower dose of heparin plus aspirin was as effective as higher dose heparin for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss. A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups. Serum samples from 320 women with chromosomally normal fetuses and from 50 women with fetuses affected by Down's syndrome were assayed retrospectively for human chorionic gonadotropin (hCG), pregnancy-specific beta 1 glycoprotein (SP1), alpha fetoprotein (AFP), and unconjugated estriol (uE3) between 14 and 21 weeks of gestation. Nonparametric discriminant analysis was applied to calculate Down syndrome risks on the basis of various combinations of serum parameters. At a risk threshold that falsely identifies 5% of controls as being affected, 46 to 48% of Down syndrome pregnancies were detected by combinations of hCG/AFP, hCG/AFP/uE3, and hCG/AFP/uE3/SP1 respectively. HCG, AFP, and uE3 were assayed in 652 serum samples from women who underwent amniocentesis because of maternal age (> or equal to 35 years in this prospective study). 49% of women with euploid fetal karyotype, 8 of 10 pregnancies with Down's syndrome, and 3 pregnancies with sex chromosomal anomalies were identified as being at an increased risk (> 1:380). It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.
                Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).
                First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.
                First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.
                Copyright 2005 Massachusetts Medical Society. High free beta human chorionic gonadotropin (beta-hCG) and low alpha-fetoprotein (AFP) levels were found in 47 Asian Down's syndrome pregnancies (median values 2.79 and 0.77 MOM, respectively). At a 5 per cent false-positive rate, free beta-hCG alone would identify 46.8 per cent of Down's syndrome pregnancies, age alone detected 34.5 per cent of affected cases, whilst AFP alone detected 17 per cent and free beta-hCG/AFP MOM ratios detected 48.9 per cent of Down's syndrome cases. When combined with maternal age-specific risk, free beta-hCG could achieve a 59.6 per cent detection rate, with AFP achieving 42.6 per cent, free beta-hCG/AFP MOM ratios 61.7 per cent, and combined free beta-hCG and AFP a detection rate of 63.8 per cent for a 5 per cent false-positive rate. Down's syndrome screening at an early gestational age (before 18 weeks) could achieve a 68 per cent detection rate with a 5 per cent false-positive rate, compared with a 59.1 per cent detection rate for a 5.2 per cent false-positive rate when screening at a late gestational age. The use of free beta-hCG in Down's syndrome screening programmes can yield an improved efficacy in the detection of Down's syndrome in an Asian population.
Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings.