Inhibin A measurement using an automated assay platform.
ABSTRACT Second-trimester measurement of maternal serum inhibin A is widely used for Down syndrome screening. To date, only a manual enzyme-linked immunosorbent assay (ELISA) produced by Diagnostic Systems Laboratories, Inc (DSL) has been available. The objective of this study was to compare the DSL assay with a new automated assay produced by Beckman Coulter, Inc (Access).
Residual serum samples from 570 women, who were receiving routine screening for Down syndrome, were retrieved from storage. The Access assay sensitivity, linearity and reproducibility were determined and a method comparison was performed. Inhibin A levels were measured using both assays. Twenty samples from women with confirmed Down syndrome pregnancy were also tested.
The Access assay had coefficients of variation of less than 10% across the range of values tested, and a sensitivity below 1 pg/mL. The DSL and Access inhibin A assay values were highly correlated (r = 0.961, r(2) = 0.923), with no apparent outliers. Inhibin A values from the Access assay were a constant 23% lower (95% CI 1-41%) than corresponding values from the DSL assay. Median values from 15 to 20 completed weeks' gestation were computed and found to be consistent with expectations. The weight-adjusted multiples of the median (MoM) levels in the unaffected pregnancies fit a log Gaussian distribution well between at least the 5th and 95th percentiles with corresponding log standard deviations of 0.1960 and 0.1919 for DSL and Access, respectively.
With median inhibin A levels appropriately calculated for the Access assay, Down syndrome screening performance is expected to be comparable to that obtained with the manual DSL assay.
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ABSTRACT: 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.Journal of Medical Screening 02/1998; 5(3):115-9. · 2.35 Impact Factor
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ABSTRACT: The value of measuring inhibin-A (a beta A dimer) with human chorionic gonadotrophin (total or the sub-units free a-hCG and free beta-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin-A was elevated in the serum of women with Down's syndrome pregnancies with a median of 1.79 multiples of the median (MOM). Using the four serum markers AFP, uE3, total hCG, and inhibin-A, in addition to maternal age, 70 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four-marker test would reduce the false-positive rate from 6-1 per cent using the triple test to 2-9 per cent. The results were virtually the same if free beta-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required to carry out the inhibin-A test were less than about [symbol: see text]3 per woman screened, the four-marker test including inhibin-A would be financially cost-effective.Prenatal Diagnosis 03/1996; 16(2):143-53. · 2.68 Impact Factor
- Journal of Medical Screening 02/2003; 10(2):56-104. · 2.35 Impact Factor