The influence of different sample collection types on the levels of markers used for Down's syndrome screening as measured by the Kryptor Immunosassay system

Author(s):  
Kevin Spencer

Background: In a rapid point-of-care screening programme for chromosomal anomalies, analysis of biochemical markers in maternal blood can now be accomplished in a rapid time frame (less than 20 min). The need to leave whole blood samples some 10 min for coagulation and a further 5 min for centrifugation adds additional processing time. Methods: The possibilities for reducing this processing time were investigated using various anticoagulated blood collection systems and the Kryptor analytical platform. Plasma levels of α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free human chronic gonadotrophin β-subunit (β-hCG) were compared with those in maternal serum. Results: From the mean results from ten patients it was shown that use of heparin plasma resulted in a statistically significant reduction in levels of PAPP-A and that EDTA plasma reduced the levels of PAPP-A dramatically. For AFP, levels in citrated plasma and EDTA plasma were also significantly reduced, whereas levels of free β-hCG were not affected. Conclusion: Use of alternative sample types for PAPP-A is not possible. The sample of choice for first trimester screening using the Kryptor platform is maternal serum.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anni Lehikoinen ◽  
Raimo Voutilainen ◽  
Jarkko Romppanen ◽  
Seppo Heinonen

Abstract Background The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use. Methods A routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9–11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11–13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed. Results Free β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups. Conclusions The present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.


Author(s):  
Gokhan Gonen ◽  
Yasam Kemal Akpak ◽  
Murat Muhcu

OBJECTIVES: This study aimed to investigate the association between first-trimester screening maternal serum markers (free human chorionic gonadotropin-beta (β-hCG), pregnancy-associated plasma protein-A, and adverse pregnancy outcomes (gestational hypertension, preeclampsia, preterm delivery, intrauterine growth restriction, oligohydramnios, intrauterine ex-fetus, abruptio placentae, and gestational diabetes mellitus). STUDY DESIGN: This was a retrospective cohort study including 1516 women who delivered a singleton pregnancy at GATA Haydarpasa Education Hospital from 2006 to 2009. Patients with multiple pregnancies, chromosome aberrations, or fetal anomalies were excluded. Extreme values of corrected- pregnancy-associated plasma protein-A and free β-hCG, and their association with adverse pregnancy outcomes were analyzed. RESULTS: Adverse pregnancy outcomes at the cutoff level of ≤0.25 c-pregnancy-associated plasma protein-A MOM values positive likelihood ratio (+LR) was 7.5 (95%CI 2.426-19.836) and had a significant correlation (r=0.108, p<0.01). It was also a significant correlation with adverse pregnancy outcomes (r=0.189, p<0.01) at the cut-off level of ≤0.50 corrected-pregnancy-associated plasma protein-A MOM values and the +LR was 2.388 (95%CI 1.889-2.991). Association between low corrected-pregnancy-associated plasma protein-A MOM values and adverse pregnancy outcomes were statistically significant and had a poor association (AUC, 0.630 95%CI 0.596-0.663, p<0.01). Preeclampsia was statistically significant, however had a fair association (AUC, 0.74 95% CI 0.690-0.802, p<0.01). Preterm birth was statistically significant but had a poor association (AUC, 0.568 95% CI 0.512-0.624, p<0.05). CONCLUSION: First-trimester maternal serum low pregnancy-associated plasma protein-A values are significantly associated with adverse pregnancy outcomes. It may be a useful tool to predictive not only chromosome anomalies but also adverse pregnancy outcomes.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jeroen L. A. Pennings ◽  
Jacqueline E. Siljee ◽  
Sandra Imholz ◽  
Sylwia Kuc ◽  
Annemieke de Vries ◽  
...  

We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fβ-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fβ-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fβ-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health.


Author(s):  
Angela Ballantyne ◽  
Lorna Rashid ◽  
Rebecca Pattenden

Background Maternal serum free beta human chorionic gonadotrophin (free β-hCG) is used as a biomarker in first trimester screening for fetal Down’s syndrome. Production of free β-hCG can occur in vitro in a time- and temperature-dependent manner; thus, the current Scottish screening protocol states samples must be received by the laboratory within 72 h. To assess the validity of the protocol, an audit was conducted to determine the impact of transit time on maternal serum free β-hCG multiple of median (MoM) values in the Scottish screened population. Methods Corrected MoM values from antenatal screening carried out over one year (April 2017 to March 2018) were stratified according to sample transit time and compared. To investigate possible environmental temperature effects, the data were split according to season and maternal serum free β-hCG concentrations from summer and winter compared. Results Of the 28,368 samples included in the study, 24,368 were received on the day of phlebotomy or after one day in transit. Only 1.5% of samples were received after 3 days in transit. The difference in maternal serum free β-hCG MoM values due to transit time was not significant. No statistical difference was found between maternal serum free β-hCG concentrations from samples collected in summer and winter months. Conclusion The current sample receipt protocol in use by the Scottish Down’s syndrome screening programme is fit for purpose.


2011 ◽  
Vol 30 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Jasmina Durković ◽  
Luka Anđelić ◽  
Bojana Mandić ◽  
Denis Lazar

False Positive Values of Biomarkers of Prenatal Screening on Chromosomopathy as Indicators of a Risky PregnancyGenetic screening on chromosomopathy has been performed on 2000 pregnant women in their first trimester of pregnancy by determining Pregnancy associated plasma protein-A and free-beta HCG biomarkers in maternal serum. After obtaining a normal fetal karyotype, the pathological values of the biomarkers have been correlated with other pregnancy disorders, and the possible causes of the positive genetic screening have been tested. 340 false positive biomarkers (17%) have been detected. The increased free-beta HCG (48.24%) had a significant influence. A significant correlation (p > 0.01) between the increased free-beta HCG and bleeding during pregnancy has been established. Complications occurred in 78.52% pregnancies with pathological biomarkers, MISSed in 13.82%, miscarriages in 10.88%, induced pregnancy terminations caused by fetal anomalies in 8.82% and births with disturbed fetal vitality in 45%. The research results have shown a significant correlation (p > 0.01) between the increased value of the free-beta HCG biomarkers and fetal hypoxia. The false positive genetic screening, caused by the increased free-beta HCG, can indicate placental dysfunction and fetal vitality disruption.


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