Feasibility of using plasma rather than serum in first and second trimester multiple marker Down's syndrome screening (original) (raw)
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Maternal serum screening for Down's syndrome in the first trimester of pregnancy
BJOG: An International Journal of Obstetrics and Gynaecology, 1995
Biochemical screening for Down's syndrome usually takes place in the second trimester of pregnancy. If effective maternal serum screening could be carried out in the first trimester, prenatal diagnosis using chorionic villous sampling (CVS) would allow for the identification of trisomy 21, and thus early pregnancy termination. Several studies have shown that alpha-fetoprotein and unconjugated oestriol (uE,) serum levels decrease in Down's syndrome pregnancies during the first trimester , while human chorionic gonadotrophin (hCG) levels are within the normal range ). In contrast with hCG, free PhCG subunit levels have been found to be increased significantly in first trimester maternal serum from Down's syndrome pregnancies .
American Journal of Obstetrics and Gynecology, 1997
The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection. STUDY DESIGN" With use of commercially available assay kits, medians for free 13-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum c~-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome. RESULTS: The mean maternal age of the study population was 35.6 --5.3 years. The best three-analyte combination was maternal serum c~-fetoprotein, free I~-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher falsepositive rate (18%) maternal serum c~-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases. CONCLUSIONS: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum c~-fetoprotein, free IS-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectiVely. (Am J Obstet Gynecol 1997;177:987-91 .) Key words: Maternal serum, Down syndrome screening It has been well established that second-trimester maternal serum levels of certain analytes are altered when the fetus has Down syndrome. Levels of maternal
Maternal serum screening for Down's syndrome in early pregnancy
BMJ, 1988
The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and a fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0-5%.
Maternal serum markers in screening for Down syndrome
Clinical Genetics, 2008
The addition of two new markers in maternal serum, estriol and HCG, to those already known, namely the level of maternal serum alfa-fetoprotein and maternal age, considerably improves the expected results of a screening strategy for Down syndrome. The detection rate is slightly increased from 53.0% to 57.6%, but, more importantly, the false-positive rate decreases from 9.4% to 7.3%. It is our belief that, at least in women aged less than 35 years, a screening strategy based on a combination of maternal age and biochemical markers should be incorporated into antenatal care. For older women, the results of such a maternal serum test may refine counseling for genetic amniocentesis, as a much more explicit risk calculation can be performed than that based on age alone.
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2005
Background: Recent NICE Guidelines have emphasized the need to have in place by 2007 the capability of offering screening to all women in the first trimester using a combination of maternal age with the ultrasound marker nuchal translucency thickness (NT) and the maternal serum biochemical markers free β-hCG and pregnancy-associated plasma protein-A (PAPP-A). Laboratories will therefore need to consider how to introduce the biochemical component of screening. With the recent launch of these assays on the DPC Immulite 2000 platform, it is appropriate and timely to investigate their clinical and analytical performance on a high throughput immunoassay analyser. Methods: Within-run and between-day precision was assessed in the normal way. Bias was assessed by comparing samples from normal pregnancies ( n = 813) and pregnancies with Down's syndrome ( n = 60) run on both the DPC system and our routine Kryptor system. Gestational day-specific medians for each marker were calculated fro...
Down syndrome maternal serum marker screening after 18 weeks of gestation: a countrywide study
American Journal of Obstetrics and Gynecology, 2013
The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. STUDY DESIGN: During the period 2007-2012, 27,648 women, regardless of maternal age (17.4% were 35 years old and over), were included in a late Down syndrome screening program (18 ϩ0 to 35 ϩ6 weeks) using the maternal serum markers alpha-fetoprotein and human chorionic gonadotrophin-beta. Samples were assayed in a single laboratory. A dataset of median markers previously established in our laboratory was used for risk calculation. The control group consisted of 27,648 women (14 ϩ0 to 17 ϩ6 weeks) randomly selected from the routine database. RESULTS: When the later screening group was compared with the standard second-trimester control group, the median multiples of medians (1.01 vs 0.98 for alpha-fetoprotein, 1.03 vs 0.98 for human chorionic gonadotrophin-beta), median risks (1 of 2414 vs 1 of 2720), false-positive rates (11.1% vs 11.6%), and trisomy 21 detection rates (83.3% vs 85.7%) did not differ significantly. CONCLUSION: Late Down syndrome maternal serum screening is feasible with a good sensitivity/specificity compromise throughout gestation and is of clinical value in late-booking women.
Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy
BJOG: An International Journal of Obstetrics and Gynaecology, 1996
To determine the value of serum screening for Down's syndrome at 8-14 weeks of pregnancy using seven potential serum markers (alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin (hCG), free a-hCG, free P-hCG, pregnancy associated plasma protein A (PAPP-A), and dimeric inhibin A). Design Stored blood samples collected from women at about 10 weeks of pregnancy, prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from pregnancies associated with Down's syndrome and from matched unaffected pregnancies.
Repeat maternal serum testing in multiple marker down's syndrome screening programmes
Prenatal Diagnosis, 1994
The effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE,) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent. A multivariate Gaussian model was used to estimate the detection and false-positive rates for Merent repeat testing policies. A policy of repeat testing those with a high risk of a Down's syndrome term pregnancy given age and marker levels would reduce the false-positive rate but there would also be a reduction in the detection rate. For example, using all three markers and a 1 in 250 cut-off risk, the estimated false-positive rate would fall from 5.3 to 3.8 per cent but the detection rate would decrease from 58 to 55 per cent. A policy of repeating those with either high or borderline risks would produce a modest improvement in screening efficiency. Repeating the 11 per cent with a risk exceeding 1 in 500 yields an estimated false-positive rate of 5.0 per cent and a detection rate of 60 per cent. A policy of selective repeat testing is not recommended as it would not substantially improve screening efficiency. Nonetheless, if a repeat test has been performed, the parameters given in this paper will enable an unbiased estimate of the Down's syndrome risk to be calculated for individual women.
Clinica Chimica Acta, 1996
A low maternal serum concentration of pregnancy associated plasma protein-A (MS-PAPP-A) in the first trimester has been suggested as a marker for the presence of a Down's syndrome (DS) fetus. We developed a time-resolved immunofluorometric assay (TrlFMA) for PAPP-A with a sensitivity < 3.9 mlU/1. In the 7-12 gestational weeks interval the median multiples of the median (MoM) was 0.57 (95%-confidence interval: 0.47-0.99) in DS pregnancies (n = 29) and lower than in controls (n = 223) (P < 0.005). The efficiency of MS-PAPP-A alone was evaluated using empirical receiver-operator-characteristics (ROC) and a sensitivity of about 25% was found for a false-positive rate of about 10% in the 7-12 gestational weeks interval. In parameterized ROC analysis a sensitivity of 9% was found for a false-positive rate of 5%. The TrlFMA PAPP-A assay seems to fulfil the quality criteria for an assay to be used in large-scale serum screening for Down's syndrome.