Evaluation of a Dried Blood Spot Assay to Measure Prenatal Screening Markers Pregnancy-Associated Plasma Protein A and Free -Subunit of Human Chorionic Gonadotropin (original) (raw)
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Archives of Gynecology and Obstetrics, 2012
Non-invasive Wrst trimester screening for fetal aneuploidy is based on the consideration of fetal nuchal translucency, biochemical serum markers 'pregnancy associated plasma protein A' (PAPP-A), and 'free beta-humane chorionic gonadotropin' (f -hCG). The blood sera of 168 pregnant women in 11 + 0 to 13 + 6 weeks of gestation were examined by both the COBAS (Roche Holding GmbH, Germany) and KRYPTOR (Brahms GmbH, Germany) immunoassay systems in two quality controlled laboratories. The concentration values were converted into multiple of median (MoM) values and compared through a two-tailed t test. The concentration values of PAPP-A diVered signiWcantly from each other (p < 0.0001). COBAS produced on average 0.09 MoM higher values in comparison to KRYPTOR (CI 95% = 0.06-0.11 MoM). In contrast, the concentration values of f -hCG did not diVer signiWcantly (p value = 0.20). The values produced by COBAS were on average only 0.02 MoM higher in comparison to KRYPTOR (CI 95% = ¡0.01 to 0.05 MoM). Which of the two systems generates the more precise results should be evaluated in a large-scale prospective study with the pregnancy outcomes.
Ultrasound in Obstetrics and Gynecology, 2010
Methods The concentrations of free β-hCG and PAPP-A were measured in samples collected from 10 pregnant women and stored as whole blood or serum for 1-8 days at 4, 20 or 40 • C. The concentrations measured were adjusted to take day-to-day variations into account and were expressed as a percentage of the values on day 0. In a second study involving 10 pregnant women, free β-hCG was measured at 10 min and at 2, 4, 8 and 12 h after collection and storage at 30 or 40 • C, either as separated serum or as whole blood.
Background: Although dried blood spots (DBS) are very convenient for massive screening, there are very few examples of their application in maternal serum screening of Down's syndrome and neural tube defects. For large-scale mass population screening in Brazil, a continental country, DBS would be fairly recommended. As there are no easily available commercial assays of AFP and hCG in DBS, the Wallac Delfia fluoroimmunometric assays intended for these biochemical markers were adapted to DBS. Methods: Serum specimens and DBS obtained from 116 pregnant women were analyzed by conventional methodology and by the adapted assays, respectively. Precision (within-run and between-run), recovery and detection limits studies were conducted Results: The non-linear regression fit of the levels of AFP and hCG in DBS by gestational age in days was described. There was a strong statistically significant correlation between the levels of these analytes in serum specimens and in DBS. For both analytes, the precision variances were compared to those presented by the manufacturer for serum samples. Conclusion: It is feasible to use these DBS adapted assays in maternal serum screening programs.
Ultrasound in Obstetrics & Gynecology, 2012
To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening. PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free β-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free β-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free β-hCG and PlGF, and detection and false-positive rates were calculated. Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P < 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample storage time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PlGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free β-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively. In pregnancies with trisomy 21 PlGF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PlGF solely for trisomy 21 screening. However, as PlGF is measured with the aim of assessing the risk for pre-eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit.
Archives of Gynecology and Obstetrics, 2007
Introduction First-trimester screening according to Nicolaides uses maternal age to obtain a common background risk for trisomy 21. The likelihood ratios by nuchal translucency, free -human chorionic gonadotropin and pregnancy-associated plasma protein-A are not with respect to maternal age. It was the aim of this study to investigate if likelihood ratios should better take care of it. Materials Pearson's correlation and diVerent models of regression analysis had been performed on the results of 8,116 Wrst-trimester screenings. The total number of pregnancies was subdivided into three subgroups of healthy fetuses (n = 8,038); fetuses with Down's syndrome (n = 46) and fetuses with other genetic abnormalities (n = 32). Statistical testing was applied to each of the three groups. Results Strong independence from maternal age could be found for each of the Wrst-trimester screening measurement parameter, as well for healthy and as for aVected fetuses. Neither Pearson's test nor nonlinear regression models could detect a correlation. Accordingly signiWcance of Pearson's test is not given.
Expert Review of Molecular Diagnostics, 2008
The modern obstetrics care includes noninvasive prenatal diagnosis testing such as first trimester screening performed between 11 and 14 weeks' gestation and second trimester screening performed between 15 and 20 weeks. In these screening tests, biochemical markers are measured in the maternal blood with or without ultrasound for fetal nuchal translucency with reported accuracy of up to 90%. Invasive procedures, including amniocentesis or chorionic villi sampling, are used to achieve over 99% accuracy. During these procedures direct fetal material is examined and, therefore, these tests are highly accurate with the caveat of a small risk for pregnancy loss. Much research now focuses on other noninvasive highly accurate and risk-free tests that will identify fetal material in the maternal blood. Fetal cells and fetal DNA/RNA provide fetal information but are hard to find in an overwhelming background of maternal cells and in the absence of specific fetal cell markers. The most experience has been accumulated with fetal rhesus and fetal sex determination from maternal blood, with an accuracy of up to 100% by using gene sequences that are absent from maternal blood. Although not clinically applicable yet, fetal cells, fetal DNA/RNA and fetal proteomics in combination with cutting edge technology are described to prenatally diagnose aneuploidies and single-gene disorders.
First and Second-Trimester Maternal Serum Analytes for the Prediction of Adverse Pregnancy Outcomes
Journal of Obstetrics, Gynecology and Cancer Research, 2021
Background & Objective: Maternal serum levels of the first-and second-trimester markers for aneuploidy have been revealed to be associated with adverse pregnancy outcomes in the absence of neural tube defects or aneuploidy. This finding can guide clinicans for early diagnosis and management of such outcomes. However, previous finding are conflicting in this regard. Therefore, this study evaluated the detection of adverse pregnancy outcomes by first-and second-trimester serum screening analytes. Materials & Methods: We prospectively recruited 972 females who underwent first and second-trimester aneuploidy screening. We gathered information on maternal demographic characteristics and serum biomarkers (free B-hCG and PAPP-A for the first-trimester; AFP, Β-hCG, Inhibin-A, and unconjugated estradiol for second-trimester). At the end of the study, adverse pregnancy outcome was recorded. Results: Abnormal screening results were reported in 34 (3.5%) patients. Two groups were significantly different in maternal age, BMI, and gestational period (P=0.017, 0.003 and 0.021, respectively). Among the measured adverse outcomes, preeclampsia was significantly more prevalent in the case group (P<0.0001). Abnormal levels of Inhibin-A is associated with the incidence of preeclampsia (RR: 29.87, CI: 13.22-67.49, P<0.0001). Additionally, patients with an abnormal level of Inhibin-A had a shorter gestational period (255.5 ± 24.53 vs. 264.79 ± 8.99, P=0.006). Likewise, patients with an abnormal level of maternal serum alpha-fetoprotein (MSAFP) had a shorter gestational period (252.0 ± 29.3 vs. 264.8 ± 8.93, P=0.001). Conclusion: First-and second-trimester maternal serum biomarkers could provide a possible screening tool for early detection of preeclampsia.