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.
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.
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.