PAPP-A Levels Research Articles

Placental proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and IGF-I and IGF-II: Levels in umbilical cord blood and associations with birth weight and length

BackgroundA newborn's birth weight for gestational age provides important insights into his or her fetal growth and well-being. While the underlying mechanisms regulating fetal growth remain to be fully elucidated, the IGF axis plays an important role. Some components of this axis have been well-characterized in umbilical cord blood, but others have not yet been studied. We measured the proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and the established molecules IGF-I and –II in umbilical cord blood to better characterize the IGF axis in relation to birth weight and length. MethodsWe performed a case-control study of 180 neonates born at a tertiary teaching hospital in Boston. To maximize power, infants were recruited in a 1:3:1 ratio with 37 SGA, 111 AGA, and 37 LGA infants matched by gestational age, sex, and delivery mode. IGF-I, IGF-II, IGFBP-4, IGFBP-5, PAPP-A, and PAPP-A2 were measured in umbilical cord blood by ELISA. Associations between birth weight and birth length Z-scores and the Z-scores of the above molecules were analyzed using linear regression models and analysis of covariance. ResultsBirth weight and length Z-scores were positively associated with Z-scores of IGF-I, IGF-II, total IGFBP-4, and IGFBP-5, with IGF-I having the strongest association. Birth weight and length Z-scores were negatively associated with Z-scores of intact IGFBP-4, PAPP-A, and PAPP-A2 levels. ConclusionsWe confirm previous findings of significant associations between the IGFs in cord blood and newborn size and for the first time show positive associations between cord blood total IGFBP-4 and -5 and birth weight and a negative association between intact IGFBP-4 and birth weight. We also show for the first time a reciprocal relationship between cord blood levels of PAPP-A and PAPP-A2 and newborn size. The implications of these findings need to be further examined in large longitudinal studies and likely have diagnostic and therapeutic potential.

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes. A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels. Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI. LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.

Circulating levels of the components of the GH/IGF-1/IGFBPs axis total and intact IGF-binding proteins (IGFBP) 3 and IGFBP 4 and total IGFBP 5, as well as PAPPA, PAPPA2 and Stanniocalcin-2 levels are not altered in response to energy deprivation and/or metreleptin administration in humans

ObjectiveIt remains unclear whether food deprivation induces changes in components of the GH/IGF-1/IGFBPs axis and if yes, which ones are mediated by leptin, an adipocyte secreted hormone regulating neuroendocrine response to energy deprivation in animals and humans. We aimed to investigate components of the axis that have not been studied to date, i.e. IGF-binding proteins (IGFBPs) and related proteases (total and intact IGFBP 3 and IGFBP 4, total IGFBP 5, PAPPA, PAPPA2 and Stanniocalcin-2), during acute (short-term fasting in healthy subjects) and chronic (women with hypothalamic amenorrhea [HA] due to excessive exercise) energy deprivation and whether metreleptin administration, in replacement, supraphysiologic or pharmacologic levels, may mediate any changes of circulating levels of the above molecules in healthy individuals and in women with hypothalamic amenorrhea. MethodsWe studied: 1) 11 healthy men and women during three four day admissions i.e. a baseline admission in the fed isocaloric state and two admissions in the complete food deprivation state for 72-h with either placebo (resulting in a hypoleptinemic state) or metreleptin administration in doses designed to normalize circulating leptin levels for the duration of the study, 2) 15 healthy men and women during three 72-hour long admissions in a complete food deprivation state receiving three escalating doses of metreleptin designed to bring circulating leptin levels to physiologic, supraphysiologic, or pharmacologic levels, and 3) 18 women with HA randomized to either metreleptin treatment in replacement doses or placebo for nine months. ResultsThere were no significant changes in the circulating profiles of the above molecules in the fasting vs. fed state and/or with metreleptin administration during acute and chronic energy deprivation. ConclusionsThe studied components of the GH/IGF-1/IGFBPs axis are not affected by energy deprivation, leptin deficiency associated with energy deprivation, or by metreleptin administration in physiologic, supraphysiologic or pharmacologic doses.

Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development.

The IGF signaling cascade exerts important regulatory functions in human ovarian folliculogenesis. The scope of this study was to evaluate the transcription profile of insulin-like growth factor (IGF) genes during human ovarian follicle development and to analyze follicle fluid levels of key IGF proteins. Gene expression profiling was performed with microarray gene analysis. The analysis was assessed from ovarian follicles and granulosa cells (GCs) obtained from isolated stage-specific human ovarian follicles, including preantral follicles, small antral follicles, and preovulatory follicles. Numerous genes involved in the IGF signaling pathway was evaluated and key genes were validated by qPCR from GCs. Protein levels of various IGF components of human follicular fluid (FF) were measured by ELISA and time-resolved immunofluorometric assays (TRIFMA). The gene expression levels of PAPPA, IGF2, IGF receptors and intracellular IGF-activated genes increased with increasing follicle size. This was especially prominent in the late preovulatory stage where IGF2 expression peaked. Protein levels of intact IGF binding protein-4 decreased significantly in FF from large preovulatory follicles compared with small antral follicles concomitant with higher protein levels of PAPP-A. The IGF modulators IGF-2 receptor, IGFBPs, stanniocalcins, and IGF-2 mRNA binding proteins were all observed to be expressed in the different follicle stages. This study confirms and highlights the importance of PAPP-A regulating bioactive IGF levels throughout folliculogenesis and especially for the high rate of granulosa cell proliferation and expression of key ovarian hormones important in the last part of the follicular phase of the menstrual cycle.

The relationships between pregnancy-associated protein A levels, placental localization and fetal birth weight

Aim. This study was designed to determine the relationship between pregnancy-associated protein A (PAPP-A), placenta localization and fetal birth weight (FBW).Materials and methods. First trimester PAPP-A levels, second trimester placental localization and birth weights of 1145 infants were obtained through a retrospective review of the patient follow up charts in Koru Hospital. Serum PAPP-A levels were recorded as the multiple of median (MоM) values, the FBW values of infants were recorded in grams, and the placental localization was recorded under seven different pre-defined categories: 1. placenta anterior; 2. placenta posterior; 3. placenta fundal; 4. placenta fundal-anterior; 5. placenta fundal-posterior; 6. placenta lateral-right; 7. placenta lateral-left. The data were analyzed using the Statistical Package for Social Sciences (SPSS) program (SPSS Inc., Chicago, IL, USA).Results.There was no significant difference between the FBW and PAPP-A levels. The comparison of seven placental localizations shows that the anterior and posterior localizations have an impact on FBW of the infants.Conclusion. The FBW was highest in the cases where the placenta was located in the corpus uteri. We believe this finding is consistent with the fact that the corpus uteri receives the largest blood supply.

Primer Hiperlipidemik ve Obez Hiperlipidemik Bayanlarda Multiplex Immunoassay Yöntemi Kullanılarak Kardiyovasküler Risk Parametrelerinin Değerlendirilmesi

Objective: In order to detect the damage caused by obesity and hyperlipidemia to the cardiovascular system in the early period, parameters that will be used for follow up of these diseases and provide information about the changes are needed. It is of course valuable to measure multiple parameters simultaneously with fast, high efficiency and less sample quantity in the measurement of these parameters. Material and Methods: We have studied serum levels of cardiovascular risk parameters sE-Selectin, follistatin, PAPP-A, sPECAM-1, pentraxin-3 and tissue factor using the multiplex immunoassay method in women primary hyperlipidemic and obese hyperlipidemic. In addition, lipid profile, liver enzymes and blood glucose were measured by routine methods. We have studied these parameters in serum of 30 healthy women, 28 primary hyperlipidemic and 32 obese hyperlipidemic women. Results: sE-selectin (p<0.01) levels were significantly higher than control group. Serum follistatin levels were significantly higher in obese hyperlipidemic group (p<0.001) in obese hyperlipidemic group and primary hyperlipidemic group (p<0.01) compared to control group. Moreover serum sPECAM-1 (p<0.001) levels were significantly higher in obese hyperlipidemic group and primary hyperlipidemic group compared to control group. There were no significant differences between serum PAPP-A, pentraxin-3 and tissue factor levels of the groups. Conclusion:Our findings suggest that hyperlipidemia associated with obesity may be the cause of cardiovascular disease rather than hyperlipidemia.

Effect of recombinant bovine somatotropin (rbST) treatment on follicular population and development in non-lactating dairy cows.

The aim of this study was to evaluate the long-term effects of recombinant bovine somatotropin (rbST) on follicle population and ovulatory follicle development in non-lactating dairy cows. Twenty-one Jersey cows were allocated in rbST (n=11) or control (n=10) groups. On day -60, cows in rbST group received 500 mg of somatotropin (s.c. Lactotropin®, Elanco). On day 0, control and rbST cows received an intravaginal progesterone-releasing device (1.9 g, CIDR®, Zoetis) and GnRH (100 mg, IM, Factrel®, Zoetis). On day 8, cows received PGF2α (25 mg, IM, Lutalyse®, Zoetis) and the CIDR® was removed. Twelve hours after device removal (D8), serum, follicular fluid and granulosa cells samples were collected. Serum and follicular concentration of estradiol (E2) and progesterone (P4) were analyzed. Total RNA was extracted from granulosa cells to measure gene expression of LHCGR, STAR, HSD-3B1, CYP11A1, CYP19A1, CYP17A1, IGFR and PAPPA by real-time PCR. Ultrasonography was performed on days -60, -53, -46, -14, -7, 0 and 8 for antral follicle count. Results were analyzed by repeated measures ANOVA and t-test. There was no effect of rbST treatment on the number of follicles during the 60 days period, as well as no effect on serum and follicular fluid E2 and follicular fluid P4 at the moment of follicle aspiration. There was a reduction in PAPPA (P = 0.006), CYP11A1 (P = 0.04) and CYP19A1 (P = 0.002) mRNA levels in granulosa cells of the pre-ovulatory follicle of rbST treated cows. In conclusion, a single dose of rbST did not have long-term effects on antral follicle population, serum and follicular E2/P4 concentrations in non-lactating dairy cows. Despite that, rbST injection decreased granulosa cell expression of genes related to steroidogenesis in the pre-ovulatory follicle.

Low levels of PAPP-A and perinatal complications

espanolObjetivo: evaluar el porcentaje de aparicion de eventos adversos perinatales en pacientes con PAPP-A baja en el primer trimestre del embarazo. En segundo plano, identificar la via y edad gestacional media de finalizacion de la gestacion. Establecer las causas de las cesareas. Realizar un protocolo de seguimiento en pacientes con PAPP-A baja. Material y metodos: Estudio longitudinal, observacional, prospectivo, descriptivo y analitico. Se evaluo a 450 gestantes con PAPP-A Resultados: El 71,6 % de las gestantes con PAPP-A Conclusiones: El porcentaje de eventos adversos en nuestras pacientes con PAPP-A baja fue elevado, presentandolos aproximadamente 7 de cada 10 gestantes. La PAPP-A baja se podria utilizar como predictor de complicaciones gestacionales, ya que se determina hoy en dia en casi todas las gestantes, y su interpretacion podria favorecer la evolucion de la gestacion, sin un aumento del coste por embarazada. EnglishObjective: the main objective was to assess the rate of occurrence of adverse perinatal events in patients with low levels of PAPP-A in the first trimester of pregnancy. The secondary objectives were to identify the route of delivery and mean gestational age at the end of pregnancy, identify the reasons for cesarean delivery, and conduct a follow-up protocol in patients with low PAPP-A. Material and methods: we performed a longitudinal, observational, prospective, descriptive, and analytical study of 450 pregnant women with PAPP-A Results: obstetric complications were detected in 71.6% of pregnant women with PAPP-A The mean gestational age at the end of pregnancy was 37 weeks. With regard to the route of delivery, 70% of patients had a vaginal delivery, while 30% of patients had a cesarean delivery. The 3 main reasons for cesarean delivery were elective cesarean (9%), suspected loss of fetal wellbeing (8.7%), and HELLP syndrome (4.9%). Conclusions: adverse events were very frequent in patients with low levels of PAPP-A (70%). Low PAPP-A could be used as a predictor of obstetric complications, since it is now determined in almost all pregnant women. Interpretation of PAPP-A findings could favor the progress of pregnancy, with no increased cost per patient.

Maternal serum screening marker levels in twin pregnancies affected by gestational diabetes.

To investigate the levels of maternal serum screening markers in the first and second trimester twin pregnancies, which subsequently developed gestational diabetes mellitus (GDM). 145 twin pregnancies were recruited in the first trimester. Stored blood samples were retrospectively tested for pregnancy-associated plasma protein (PAPP)-A, human chorionic gonadotrophin (hCG), placental growth factor (PlGF), placental protein (PP)13, α-fetoprotein (aFP) and inhibin A. Values were expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight and parity, as appropriate. Twenty samples of first and second trimester were available from 11 twins who subsequently developed GDM and 219 samples from unaffected twins. The median PAPP-A level in the affected twins was 3.61 MoM compared with 2.46 MoM in unaffected twins (P < 0.001, Wilcoxon rank sum test, two tailed); significant results were found in both trimesters. The median PP13 was also increased but to a lesser extent. It was only statistically significant overall (P < 0.05) and in second trimester samples (P < 0.02). No other marker differed significantly. Logistic regression found that combining PAPP-A and maternal weight had a 55% detection rate for a 10% false-positive rate. Early prenatal marker evaluation in twin pregnancies can be also useful for predicting the risk for developing GDM and should be further investigated.

Microarray analysis: First-trimester maternal serum free β-hCG and the risk of significant copy number variants.

To determine whether abnormal levels of first-trimester maternal serum free β-hCG and PAPP-A are associated with significant copy number variants (CNVs) on chromosomal microarray analysis (CMA). Retrospective cohort of singleton prenatal CMA studies (n=2880). Cases with an abnormal karyotype, benign familial or de novo variants, and absence of heterozygosity were excluded. The prevalence of abnormal serum analytes was compared between patients with significant CNVs (n=56) and those with normal CMA (n=884). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using Fisher's exact test. Mantel-Haenszel method was utilized to adjust ORs for prenatal diagnostic procedure type and indications for testing. Statistical significance was determined as P value<0.05. Abnormally low serum free β-hCG (≤0.45 MoM) was associated with an increased risk of significant CNVs (OR 3.53, 95% CI, 1.25-8.66, P<0.01). This association remained significant after adjusting for abnormal nuchal translucency and advanced maternal age (AMA) (adjusted OR 3.04, 95% CI, 1.05-7.48, P<0.05) or procedure type and AMA (adjusted OR 3.21, 95% CI 1.13-8.16, P<0.05). The associations of abnormally high serum free β-hCG, low PAPP-A, and high PAPP-A with significant CNVs were not statistically significant. Low first-trimester serum β-hCG is associated with an increased risk of significant CNVs on CMA.

Depot-specific and GH-dependent regulation of IGF binding protein-4, pregnancy-associated plasma protein-A, and stanniocalcin-2 in murine adipose tissue

IntroductionPregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF)-I action through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. Most members of the IGF system are expressed in adipose tissue (AT), but there is a relative paucity of information on the distribution of IGFBP-4, PAPP-A, and STC2 in different AT depots. Since IGF-I expression in AT is highly GH-dependent, we used bovine GH transgenic (bGH) and GH receptor knockout (GHR−/−) mice to investigate AT depot-specific expression patterns of IGFBP-4, PAPP-A, and STC2, and whether the regulation is GH-dependent. MethodsSeven-month-old male bGH, GHR−/− and wild type (WT) control mice were used. Body composition was determined, and subcutaneous, epididymal, retroperitoneal, mesenteric and brown adipose tissue (BAT) depots were collected. RNA expression of Igfbp4, Pappa, and Stc2 was assessed by reverse transcription quantitative PCR and IGFBP-4 protein by Western blotting. ResultsIgfbp4, Pappa, and Stc2 RNA levels were differentially expressed in an AT depot-dependent manner in WT mice. Igfbp4 RNA levels were significantly higher in all white AT depots than in BAT. Pappa was most highly expressed in the mesenteric depot: levels were 7.5-fold higher in mesenteric than in subcutaneous AT (p < .001). Although intraabdominal in origin, epididymal and retroperitoneal Pappa expression levels were 69% and 68% lower, respectively, as compared to mesenteric levels (p < .001). Stc2 RNA expression was significantly higher in all intraabdominal white AT as compared to subcutaneous AT and BAT; levels in epididymal, retroperitoneal, and mesenteric were all more than three-fold higher than in subcutaneous AT (p < .001) and 12-fold higher than in BAT (p < .001). Gene expression patterns in bGH and GHR−/− mice mimicked those in WT mice, suggesting that GH does not affect the transcription of the STC2-PAPP-A-IGFBP-4-axis in AT. However, proteins levels of intact IGFBP-4 were significantly increased in bGH mice and decreased in GHR−/− mice, whereas the PAPP-A-generated IGFBP-4 fragment level was unaltered. ConclusionExpression of Igfbp4, Pappa, and Stc2 differ between AT depots and is generally higher in white AT than in BAT. The transcription appears to occur in a GH-independent manner, whereas IGFBP-4 protein levels are highly influenced by altered GH activity.

Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors

Objective The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). Material and Methods We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. Results The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion WBC appears to be a useful method of atherosclerosis prevention in AS patients.

Уровень рарр-а в i триместре и исход беременности у первородящих

Уровень рарр-а в i триместре и исход беременности у первородящих

Does the deficiency of 25-hydroxy vitamin D effect the placental peptides (free β-human chorionic gonadotropin and pregnancy-associated plasma protein A ) levels ?

SummaryObjectiveIn this study, we analysed that low maternal 25 hydroxy vitamin D (25(OH)D) levels cause an increase in the level of 1,25 dihydroxy vitamin D in the syncytiotrophoblasts by placental hydroxilation and also we analysed the effects of low syncystiotrofoblastic stimulation on placental peptides (free β-human chorionic gonadotropin and pregnancy-associated plasma protein A) secretion..Material and MethodsThis retrospective study was included 225 pregnant women at 11-14 weeks of gestation attending the outpatient clinic of our hospital for first trimester screening test from January 2017 to December 2017. Vitamin D levels were deficient in 145 pregnant women and adequate in 80 pregnant women. Serum 25(OH)D concentrations were measured at 11–14 weeks gestation in 225 singleton pregnancies using liquid chromatography-tandem mass spectrometry in the same labaratory. We assessed the relationship between vitamin D, free β-human chorionic gonadotropin ( free β-hCG) and pregnancy associated plasma protein A (PAPP-A) levels during pregnancy.Results: There was a negative correlation between PAPP-A levels and maternal age at sampling (p=0.219). There was a positive correlation between free β-hCG levels and maternal age at sampling (p=0.034). There was a negative correlation between Low 25(OH)D levels and free β-hCG levels (p=0.071). There was a positive correlation between Low 25(OH)D levels and PAPP-A levels (p=0.414).Conclusion There was no statistically significant relationship between free β-hCG, PAPP-A levels and vitamin D in the first trimester.

17 - Determination of serum level of PAPP-A in patients with clear cell renal cell carcinoma

17 - Determination of serum level of PAPP-A in patients with clear cell renal cell carcinoma

Impact of early supplementation with low-dose aspirin on functional first trimester parameters in low-risk pregnancies

Introduction: There is recent evidence that prophylaxis with 150 mg of aspirin given before 14–16 weeks significantly reduces preeclampsia rates and may improve pregnancy outcome. We conducted an observational study that investigates the effect of low-dose aspirin initiated early in pregnancy or in preconception on functional parameters assessed at 11–14 weeks. Materials and methods: We have retrospectively selected 128 pregnant women that presented for the first trimester screening for aneuploidies between 11+0 and 13+6 weeks of gestation and received low-dose aspirin before 14 weeks. We excluded cases with an estimated high risk for early preeclampsia (cut-off > 1:100). This group was matched to 1044 cases that did not receive aspirin in early pregnancy. We have selected for statistical analysis maternal parameters, ultrasound parameters (crown-rump length, nuchal translucency thickness, pulsatility index in uterine arteries – left, right, average and average uterine PI expressed in multiple of median (MoM)), first trimester maternal biochemical markers (free β hCG and PAPP-A expressed in MoM), and the calculated risk for early onset and late onset preeclampsia. Results: The most common dosages of aspirin were 75 mg (77 cases) and 100 mg (32 cases). The most significant results are within the aspirin group. In the subgroup that received aspirin before 11 weeks (110 cases), irrespective of the dosage, the uterine blood flow is significantly improved (average uterine PI 1.7 compared with 2.22, p < .05, (0.24–0.7) 95% CI) and the PAPP-A levels are higher (1.2 compared with 0.82, p > .05, [(−0.65) − 0.02] 95% CI). The estimated risk for both early and late onset preeclampsia in this group is reduced (1:2141 compared with 1:333 for early preeclampsia, p < .05, (1216–2398) 95% CI; 1:361 compared with 1:99 for late onset preeclampsia, p < .05, (173–351) 95% CI). Conclusion: Even though the results are not always statistically significant, they demonstrate that placentation parameters improve with higher doses of aspirin started before 11 weeks.

Strong impact of ethnicity on effectiveness of the first trimester maternal serum screen of fetal Down syndrome

Objectives: The objective of this study is to compare the effectiveness of first-trimester maternal serum screening (MSS) for fetal Down syndrome among Thai women between the method using Caucasian reference ranges with racial factor correction (CRR-RC) and that using Thai reference ranges (TRR).Methods: A prospective database of MSS was accessed. The levels of PAPP-A and beta-hCG were calculated to determine their MoMs (multiple of medians) by two methods: (1) CRR-RC for Asian women and (2) TRR. The MoMs from both methods were used to determine the fetal risk.Results: Of 24,885 women including 36 fetuses with Down syndrome, the detection rates were significantly higher with TRR when compared with CRR-RC, 77.8 and 63.9%, respectively, p < .001. Additionally, the false-positive rates were significantly lower with TRR when compared to CRR-RC (7.5 versus 12.5%, respectively, p < .001)Conclusions: The effectiveness of MSS was much better by using our own reference ranges rather than the method of racial factor correction. The important insight is that ethnicity strongly impacts on the effectiveness that cannot be completely corrected by ethnic factor. MSS derived by the CRR-RC in other regions should be interpreted with high precaution, especially where the biophysical characteristics of the women are much different from Caucasian population.

Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause

The purpose of this study is to confirm a difference in the first-trimester screen maternal biochemistry and false-positive rates (FPR) between pregnancies conceived spontaneously and those conceived via assisted reproductive technologies (ART). Retrospective analysis of the complete population of women (17,889 pregnancies) who had undergone first-trimester screening between January 2004 and September 2009 at three private ultrasound clinics in Queensland, Australia was used in the study. The age, gestation, method of conception, ultrasound markers, biochemistry markers (PAPP-A, fβ-hCG), and type of biochemical analyzer platform (Brahms Kryptor, Immulite 2000) data was collated. Univariate analysis of variance (ANOVA), Spearman's rank nonparametric correlation analysis, and Binary Logistic Regression analysis were used to analyze data. Spontaneous pregnancies were used as controls. Results were considered significant when the p value was less than 0.05. After exclusions, 16,363 singleton pregnancies, including 1543 conceived via ART, were analyzed. Results from the two biochemistry platforms, Brahms Kryptor and Immulite 2000 were significantly different (p<0.001); thus, the data was divided for analysis purposes. PAPP-A was universally significantly lower in IVF pregnancies compared to spontaneously conceived pregnancies (p<0.001). Using the Brahms Kryptor platform, ICSI was associated with significantly decreased PAPP-A (p<0.046), and a significantly increased FPR (p=0.012). Consistent with previous studies IVF pregnancies had significantly lower PAPP-A levels supporting the need to appropriately adjust the combined first-trimester screening (cFTS) risk algorithm for IVF conceptions. The Brahms Kryptor and Immulite 2000 platforms are significantly different; however, the universally lower PAPP-A findings support the hypothesis that the lower PAPP-A is due to a biological cause.

Chorionic thickness and PlGF concentrations as early predictors of small-for-gestational age birth weight in a low risk population.

SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11-13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. The study included 76 patients at 11-13 (+ 6d) gestational weeks, monitored throughout preg-nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11-13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.

PROGNOSIS OF ONE-DAY MORTALITY AND PROTEIN GROWTH AND DAMAGE FACTORS IN ACUTE CORONARY SYNDROME

Aim. To perform comparative analysis of the pregnancy-associated plasma protein A and insulin-like growth factor 1 (PAPP-A and IGF-1) in blood plasma of patients with acute coronary syndrome (ACS). Prediction of 24-hour risk of fatal outcome in ACS. Material and methods. The concentrations of PAPP-A and IGF-I were assessed in 71 ACS patients, mean age 57 y. o. In the study group, during 24 hours myocardial infarction (MI) was diagnosed in 44, unstable angina in 27, and 9 fatal outcomes. Also, the concentrations of PAPP-A and IGF-I were measured in comparison and control groups. Comparison consisted of 40 hypertension patients with stable ischemic heart disease. Controls were 20 almost healthy persons. Results. In the study, there was increase of PAPP-A and IGF-I levels in ACS patients. In unstable angina patients PAPP-A is higher than in controls 3,56 times, and in MI patients 11,6 times. In MI, PAPP-A is 3,2 times higher than in unstable angina. In unstable angina patients there the highest levels of IGF-I, and 1,27 higher than in controls. In the study, we showed that IGF-I and PAPP-A levels in acute coronary pathology are linked to the outcome at the first day of the disease. Conclusion. It is aim full to apply PAPP-A and IGF-I to urgent cardiology practice as an analyzer of atherosclerotic plaque instability in acute coronary events, as a factor of life and disease prognosis.