ABSTRACT
OBJECTIVE: To evaluate the role of PP13 as a marker for pre-eclampsia (PE) by comparing two different immunoassay platforms. METHODS: In this case-control study, first-trimester serum samples from 195 normal pregnancies and 37 pregnancies with PE were analysed for PP13 by using a manual DTL ELISA and the AutoDELFIA(®) platform. RESULTS: Levels of PP13 in first-trimester pregnancies increased with gestational age in controls and pre-eclampsia cases using both methods of analysis, but at different rates. PP13 levels were decreased in women with PE. Levels of the marker are found to be more reduced in PE cases when measured using the DTL ELISA compared to AutoDELFIA(®). CONCLUSION: Further studies are needed to compare the performance of the DTL ELISA and the AutoDELFIA(®) PP13 assays in terms of reproducibility, robustness and clinical performance in predicting pre-eclampsia.
Subject(s)
Diagnostic Techniques, Obstetrical and Gynecological , Galectins/blood , Pre-Eclampsia/blood , Pregnancy Proteins/blood , Pregnancy Trimester, First/blood , Adult , Biomarkers/analysis , Biomarkers/blood , Case-Control Studies , Diagnostic Techniques, Obstetrical and Gynecological/instrumentation , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Female , Galectins/analysis , Gestational Age , Humans , Pregnancy , Pregnancy Proteins/analysis , Sensitivity and SpecificityABSTRACT
OBJECTIVES: To measure maternal serum placental growth factor (PlGF) levels in trisomy 21 cases and controls in samples drawn before 11 weeks' gestation. METHODS: Early first-trimester maternal serum samples, drawn between 8 + 0 and 10 + 6 weeks' gestation, for 37 trisomy 21 cases and 244 unaffected controls were retrieved from frozen storage, and PlGF was retrospectively measured using a DELFIA Xpress immunoassay platform. PlGF levels were converted to multiples of the median (MoM), and trisomy 21 and unaffected groups were compared. RESULTS: Raw PlGF and MoM levels were significantly higher in the maternal serum of trisomy 21 cases than in controls over the 3-week gestational window (unaffected 1.0 MoM compared with trisomy 21 1.3 MoM (P < 0.0001)). However at 8 completed weeks of gestation the increase was most significant and at 10 completed weeks there was no significant difference between trisomy 21 and unaffected PlGF levels. CONCLUSIONS: Early PlGF levels in maternal serum in trisomy 21 cases may be increased relative to unaffected controls, however, the relationship between PlGF levels and gestational age in trisomy 21 and unaffected pregnancies in the first two trimesters of pregnancy appears to be complex and requires further study.
Subject(s)
Chorionic Gonadotropin, beta Subunit, Human/blood , Down Syndrome/blood , Pregnancy Proteins/blood , Pregnancy-Associated Plasma Protein-A/metabolism , Adult , Biomarkers/blood , Denmark , Female , Humans , Mass Screening , Maternal Age , Nuchal Translucency Measurement , Placenta Growth Factor , Pregnancy , Pregnancy Trimester, First/blood , Retrospective StudiesABSTRACT
OBJECTIVE: To assess the impact of early vaginal bleeding on the levels of markers used in first trimester screening for aneuploidy. METHODS: A retrospective analysis was carried out on the free beta human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency thickness in 49 653 women with a normal singleton fetus who had first trimester combined screening for Down Syndrome in three centres. Median MoMs and the distribution of log MoMs of the two markers were compared in two groups-7470 women who self-reported vaginal bleeding and 42 183 women who reported no vaginal bleeding at any stage prior to the screening test. RESULTS: The overall median MoM free beta-hCG and that in the bleeding and non-bleeding group were 0.9854, 1.0012 and 0.9832, and for PAPP-A were 1.0407, 1.0413 and 1.037. There was no significant difference between the bleeding and non-bleeding group by median test (p = 0.080) or by t-test comparing log MoMs (p = 0.1305) for free beta-hCG and for PAPP-A with median test (p = 0.5071) or by t-test comparing log MoMs (p = 0.1740). For delta nuchal translucency (NT) there was also no significant difference between the bleeding and non-bleeding group (p = 0.055). CONCLUSION: Vaginal bleeding has little or no impact on first trimester marker levels and no correction is necessary.
Subject(s)
Aneuploidy , Biomarkers/analysis , Genetic Testing/methods , Pregnancy Trimester, First/blood , Uterine Hemorrhage/blood , Adult , Biomarkers/blood , Chorionic Gonadotropin, beta Subunit, Human/analysis , Chorionic Gonadotropin, beta Subunit, Human/blood , Female , Genetic Testing/standards , Humans , Pregnancy , Pregnancy Trimester, First/genetics , Pregnancy-Associated Plasma Protein-A/analysis , Prenatal Diagnosis/methods , Prenatal Diagnosis/standards , Retrospective Studies , Time Factors , Uterine Hemorrhage/epidemiology , Uterine Hemorrhage/geneticsABSTRACT
BACKGROUND: Maternal serum A Disintergrin And Metaloprotease-12 (ADAM-12) has been proposed as a marker for prenatal screening of chromosomal abnormalities, pre-eclampsia and other adverse pregnancy outcomes. In this study, we examine the stability of ADAM-12 with time and at different temperatures. METHODS: Maternal serum and whole blood pools were stored at 30 degrees C, room temperature and refrigerator temperature or subjected to repeated freeze-thaw cycles. ADAM-12 was measured at set time points using an automated DELFIA research assay. RESULTS: Using a 10% change in concentration as a limit of stability, ADAM-12 is stable in serum for less than 15 h at 30 degrees C, less than 20 h at room temperature and for 51 h at refrigerator temperature. ADAM-12 levels are not altered following three - 20 degrees C to room temperature freeze-thaw cycles. The stability of ADAM-12 in whole blood appears similar to that in serum. CONCLUSIONS: The findings of this study suggest that ADAM-12 may be unstable under many routine laboratory conditions, and the marker's instability may also be partly responsible for the discrepancies in the literature.
Subject(s)
ADAM Proteins/metabolism , Membrane Proteins/metabolism , Pregnancy Trimester, First/blood , ADAM Proteins/blood , ADAM12 Protein , Biomarkers/blood , Biomarkers/metabolism , Blood Specimen Collection/methods , Blood Specimen Collection/standards , Down Syndrome/blood , Down Syndrome/diagnosis , False Positive Reactions , Female , Gestational Age , Humans , Membrane Proteins/blood , Mothers , Pregnancy , Pregnancy Trimester, First/metabolism , Pregnancy Trimester, Second/blood , Pregnancy Trimester, Second/metabolism , Prenatal Diagnosis/methods , Prenatal Diagnosis/standards , Protein StabilityABSTRACT
OBJECTIVE: The objective of this study was to examine first-trimester maternal serum placental growth factor (PlGF) levels in pregnancies which later develop hypertensive and growth complications. METHODS: In this case-control study, PlGF levels were measured by AutoDELFIA immunoassay platform. There were 47 cases of at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age (SGA), haemolysis elevated liver enzymes and low platelets (HELLP) and gestational hypertension (GH) and 452 matched controls. RESULTS: PlGF levels were significantly lower in cases of all PE, early PE, HELLP, all SGA, early SGA and SGA without PE, but not in GH, late PE, late SGA, PE with SGA or PE without SGA or HELLP. CONCLUSION: Low levels of first-trimester PlGF provide a good indicator of SGA complications and some hypertensive disorders, in particular severe cases of PE such as early onset and HELLP syndrome.
Subject(s)
Fetal Growth Retardation/diagnosis , Hypertension, Pregnancy-Induced/diagnosis , Infant, Small for Gestational Age , Pregnancy Proteins/analysis , Pregnancy Trimester, First/blood , Adult , Biomarkers/analysis , Biomarkers/blood , Case-Control Studies , Female , Fetal Growth Retardation/blood , Gestational Age , Humans , Hypertension, Pregnancy-Induced/blood , Infant, Newborn , Infant, Small for Gestational Age/blood , Models, Biological , Placenta Growth Factor , Pregnancy , Pregnancy Outcome , Pregnancy Proteins/blood , Prenatal Diagnosis/methods , PrognosisABSTRACT
BACKGROUND: Maternal serum placental protein 13 (PP13) has been proposed as a marker for prenatal screening of pre-eclampsia (PE) and other adverse pregnancy outcomes. This study aims to examine the stability of PP13 at different routine temperatures. METHODS: Maternal serum pools and whole blood samples were stored at '30 degrees C', room temperature or refrigerator temperature. Further, serum pools were also subjected to repeated freeze-thaw cycles. PP13 was measured at set time points using an AutoDELFIA research assay. RESULTS: Levels of PP13 are stable, defined as less than 10% change in concentration, in serum for 17.4 h at '30 degrees C', 3.4 days at room temperature and for at least 34 days at refrigerator temperature. PP13 concentration is not altered following three -20 degrees C to room temperature freeze-thaw cycles. PP13 is stable in whole blood for at least 3 days at all three temperatures studied. CONCLUSIONS: PP13 is a suitably stable molecule and can be treated under routine laboratory and normal transport temperatures.
Subject(s)
Galectins/blood , Galectins/metabolism , Pregnancy Proteins/blood , Pregnancy Proteins/metabolism , Pregnancy Trimester, First/blood , Blood Preservation/adverse effects , Blood Preservation/methods , Blood Specimen Collection/adverse effects , Blood Specimen Collection/methods , Diagnostic Tests, Routine/methods , Female , Gestational Age , Humans , Mothers , Pregnancy , Pregnancy Trimester, First/metabolism , Prenatal Diagnosis/methods , Protein Stability , Serum/chemistry , Serum/metabolism , Temperature , Time FactorsABSTRACT
OBJECTIVE: To examine placental growth factor (PlGF) levels in first trimester maternal serum in trisomy 21 pregnancies and to investigate the potential value of PlGF in a first trimester screening test. METHODS: First trimester maternal serum from 70 trisomy 21 cases and 375 euploid controls were retrospectively analyzed for PlGF using a DELFIA Xpress immunoassay platform. Results were expressed as multiples of medians (MoM) for comparison. RESULTS: PlGF levels were significantly decreased in pregnancies with trisomy 21, 0.76 MoM versus 0.98 MoM in controls. Inclusion of PlGF into the first trimester combined test [maternal age, pregnancy associated plasma protein-A (PAPP-A), free-beta human chorionic gonadotrophin (beta-hCG) and nuchal translucency] would increase the detection rate by 0.5% at a 5% false positive rate. CONCLUSION: PlGF at 11 weeks to 13 weeks 6 days has the potential to be included as a marker for the detection of pregnancies with trisomy 21.
Subject(s)
Down Syndrome/blood , Pregnancy Proteins/blood , Pregnancy Trimester, First/blood , Biomarkers/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Down Syndrome/diagnostic imaging , Female , Gestational Age , Humans , Maternal Age , Middle Aged , Nuchal Translucency Measurement , Placenta Growth Factor , Pregnancy , Pregnancy-Associated Plasma Protein-A/analysis , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate first-trimester ADAM-12 levels in pregnancies which later develop hypertensive and growth complications. METHODS: First-trimester serum samples (11(+0) to 13(+6) weeks) were retrieved from frozen storage. 47 samples with at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age, HELLP syndrome and gestational hypertension were analysed and 452 controls matched to the cases by gestational age and length of storage were analysed. ADAM-12 levels were measured by the automated AutoDELFIA immunoassay platform. RESULTS: ADAM-12 was found to increase with gestational age (11(+0) to 13(+6) weeks) and decrease with increasing maternal weight and in women who smoked. After correction, ADAM-12 median multiples of the median were increased in cases with HELLP syndrome, all PE and PE only. CONCLUSION: The increased first-trimester levels of ADAM-12 in PE and HELLP are in contrast with previous findings. The usefulness of ADAM-12 as a marker for adverse outcomes is still unclear.
