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Context Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown. Objective We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment. Methods Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children. Results Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio. Conclusion The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients. [ABSTRACT FROM AUTHOR]

One of the most vital processes of the body is the cardiovascular system's proper operation. Physiological processes in the heart are regulated by the balance of cardioprotective and pathological mechanisms. The insulin-like growth factor system (IGF system, IGF signaling pathway) plays a pivotal role in regulating growth and development of various cells and tissues. In myocardium, the IGF system provides cardioprotective effects as well as participates in pathological processes. This review summarizes recent data on the role of IGF signaling in cardioprotection and pathogenesis of various cardiovascular diseases, as well as analyzes severity of these effects in various scenarios. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a pregnancy‐related diabetic condition that may cause serious complications. However, its pathogenesis remains unclear. Placental damage due to GDM may lead to several health issues that cannot be ignored. Thus, we aimed to identify the mechanisms underlying GDM by screening differentially expressed genes (DEGs) related to vascular endothelial cells in the GDM databases and verify the expression of these DEGs in the placentas of women afflicted by GDM. Methods: We used GDM microarray datasets integrated from the Gene Expression Omnibus (GEO) database. Functional annotation and protein–protein interaction (PPI) analyses were used to screen DEGs. Placental tissues from 20 pregnant women with GDM and 20 healthy pregnant women were collected, and differential gene expression in the placental tissues was verified via qRT‐PCR, western blotting, and immunofluorescence. Results: Bioinformatics analysis revealed three significant DEGs: SNAIL2, PAPP-A, and TGFβ1. These genes were all predicted to be underexpressed in patients with GDM. The results of qRT‐PCR, western blot, and immunofluorescence analyses indicated that SNAIL2 and PAPP‐A in the placenta tissue of patients with GDM were significantly underexpressed. However, TGFβ1 in the placenta tissues of GDM was significantly overexpressed. Conclusion: SNAIL2, TGFβ1, and PAPP‐A may affect the placentas of pregnant women with GDM, warranting further investigation. [ABSTRACT FROM AUTHOR]

Introductıon: PAPP-A (Pregnancy-associated plasma protein-A) is considered a pro-inflammatory marker and its serum levels are elevated in non-pregnant patients with asthma. In the current research, we aimed to investigate whether maternal serum PAPP-A levels, a biomarker for first-trimester aneuploidy screening, differ in pregnant women with asthma compared to healthy pregnant women. Methods: In the first step, maternal serum PAPP-A MoM values, used as the first-trimester fetal aneuploidy screening marker, were compared between pregnant women with asthma and a healthy pregnant group. In the second step, the groups compared whether PAPP-A and fβ-HCG ( free β human chorionic gonadotropin) levels were below or above the cut-off values for Trisomy 21 and compared them according to maternal age (<35; ≥35). Results: The median PAPP-A level was found to be 2.15 IU/L (0.41-9.91) in the asthma group and 2.54 IU/L (0.56-11.40) in the control group, and there was no difference between the groups (P=0.363). The median PAPP-A MoM value was 0.99 (0.15-3.28) in the asthma group and 1.07 (0.33-3.37) in the control group. This result did not show a statistically significant difference (P = 0.694). No statistically significant difference was shown between the groups below and above 35 age (P=0.456). Conclusion: Maternal serum PAPP-A levels in pregnant women with asthma do not vary compared to the healthy pregnant group without asthma. Based on the results of our study, the first-trimester fetal aneuploidy screening test is a reliable screening method for pregnant women with asthma. [ABSTRACT FROM AUTHOR]

Introduction: Hypertensive disorder of pregnancy is a mysterious condition. Even after extensive research, it is associated with high maternal as well as perinatal mortality and morbidity. The origin of hypertension in pregnancy is thought to be lying in the placenta. β-hCG and PAPP-A are glycoproteins produced from placenta. Therefore, these values are reported to be altered in hypertensive disorders of pregnancy. Aim and Objective: To determine the predictive value of early trimester serum β-hCG and PAPP-A levels for the development of hypertensive disorders of pregnancy. Materials and Methods: This is a prospective cohort study conducted at IMS and SUM Hospital, Bhubaneswar. Maternal serum β-hCG and PAPP-A levels were measured in all the singleton pregnant women at 11 + 0–13 + 6 weeks. All these women were followed up till delivery to find out the development of hypertension. The outcome was matched with their respective biochemical markers and analyzed. Results : Mean value for maternal serum β-hCG of the study population was found to be 48.95 ng/ml with a range of 2–210 ng/ml. Hence, maternal serum β-hCG value during 11–13 weeks of pregnancy shows no correlation with the development of HDP later in pregnancy. The mean value of maternal serum β-hCG for women who developed HDP and those who did not develop the pathology was 48.13 ng/ml and 49.78 ng/ml, respectively (p = 0.61). Mean value of serum PAPP-A for the normotensive group was found to be 5.12 mIU/ml and 3.76 mIU/ml for women who developed HDP (p < 0.01). Conclusion : Low maternal serum PAPP-A determined at 11 + 0–13 + 6 weeks has a better predictive value for the development of hypertensive disorders in pregnancy than β-hCG. [ABSTRACT FROM AUTHOR]

Copyright of Ginecologia.ro is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Placenta accreta (PA) is a serious obstetric complication associated with maternal morbidity and mortality. While ultrasonography and MRI are effective in the third trimester, early diagnosis in the first two trimesters remains elusive. This study aims to explore the utility of biochemical markers in early PA detection, addressing a critical gap in current diagnostic approaches. A retrospective analysis was conducted on patients diagnosed with placenta previa between October 2021 and December 2022. Cases were divided into PA and non-PA groups based on histopathological examination. Demographic, obstetric characteristics and serum analytes were compared between the groups to identify potential biomarkers for early PA detection. Patients with PA exhibited higher gravida, parity, and abortion numbers. First-trimester free β-hCG levels and second-trimester E3 levels were significantly elevated in the PA group compared to non-accreta cases. No significant differences were observed in PAPP-A, AFP, and second-trimester hCG levels. Additionally, postoperative leukocyte count was lower, and intrapartum bleeding frequency was higher in the PA group. Multiparity and the number of previous cesarean sections emerged as significant risk factors for PA, consistent with previous literature. While previous studies reported associations between biochemical markers and PA, this study uniquely identified significant associations with free β-hCG and E3 levels. Further research is warranted to validate these findings and elucidate their clinical implications [ABSTRACT FROM AUTHOR]

Background: To investigate the role of pregnant-associatedplasma protein A (PAPP-A) and uterine artery Doppler ultrasound in predicting fetal growth restriction (FGR). Materials and Methods: In total, 120 pregnant women diagnosed with FGR in Shijiazhuang Obstetrics and Gynecology Hospital from January 2021 to December 2023 were selected as the FGR group, and 120 normal pregnant women were selected as the control group during the identical time frame. Maternal serum pregnancyrelated protein A combined with uterine artery Doppler ultrasonography was performed during the period from the 11th, to the 13th+6 weeks of pregnancy. The course of pregnancy was observed in both groups of pregnant women. Results: The FGR group exhibited significantly reduced rates of vaginal delivery and fetal survival compared to the control group, while experiencing higher rates of preterm delivery and cesarean section, with statistical significance (P<0.001). The pulsatility index of the uterine artery (UtA-PI) and the resistance index of the uterine artery and the FGR group exhibited a higher proportion of early blood diastolic incisors compared to the normal group, with statistical significance noted at a level of P<0.001. The concentration of PAPP-A was lower than that of normal group (P<0.001). The sensitivity of combining UtA-PI and PAPP-A to predict FGR was 81.6%, and the sensitivity of combining UtA-PI and PAPP-A is 82.9%, which is 1.3% higher, but there was no statistically significant distinction between the two approaches (P>0.05). Conclusion: The implementation the combination between PAPP-A and Doppler ultrasound is an effective method to predict FGR. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the relationship between maternal serum PAPP-A (pregnancy-associated plasma protein A) and free ß-hCG (human chorionic gonadotropin) values with fetal birth weight. Material and Methods: 554 patients who applied to Yıldırım Beyazit University Atatürk Training and Research Hospital Obstetrics Clinic between January 2009 and December 2016 for first trimester combined screening tests were included in the study. Antenatal follow-up and pregnancy outcomes were examined. The relationship between adjusted multiples of median (MoM) values of maternal serum PAPP-A and free ß-hCG levels and fetal birth weight (FBW); small for gestational age (SGA--fetal birth weight <10th percentile) and large for gestational age (LGA--fetal birth weight > 90th percentile) were analyzed. Results: Maternal serum PAPP-A level was found to have a relationship with SGA development (p=0.03). Every decrease per unit in the adjusted MoM value of maternal serum PAPP-A level increases the risk of SGA development three times (RR, 1/0.333; 95% CI, 0.1-0.8, p=0.030). Conclusion: Correlation between PAPP-A value and SGA was found to be statistically significant. However, a similar prediction was not eligible between maternal serum PAPP-A level and LGA fetuses. On the other hand, maternal serum free ß-hCG level did not have a statistical significance as a predictor for both SGA and LGA fetuses. [ABSTRACT FROM AUTHOR]

Copyright of Istanbul Gelisim University Journal of Health Sciences / İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi is the property of Istanbul Gelisim Universitesi Saglik Bilimleri Yuksekokulu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: According to WHO, hypertensive disease is the leading cause of direct maternal mortality accounting for 10–25% in developing countries (James in Heart, 90(12):1499–504). This study compares the combinations of mean arterial pressure (MAP) and uterine artery doppler (UAD) versus serum-free β HCG, pregnancy-associated plasma protein-A, and placental growth factor (PlGF) versus a combination of all variables at 11 to 13+6 as long-term predictors of pregnancy-induced hypertension (PIH). Materials and Methods: A prospective, observational cohort study recruited 97 primigravidae at 11 to 13+6 weeks gestation at GMCH. Follow-up was done at 32–34 weeks and before delivery. Development of PIH, mode of delivery, birthweight, maternal and fetal adverse outcomes were documented, analyzed and compared among three groups. In Group A-biophysical markers, Group B-biochemical markers and in Group C all variables were used. Results: The mean age, maternal weight, height and BMI of patients developing gestational hypertension were 30 ± 5 years, 64.3 ± 12.5 kg, 155.8 ± 5.5 cm and 26.4 ± 4.1, respectively. Out of the 3, Group C is the best screening test for predicting the overall chance of development of gestational hypertension with a sensitivity of 97.37% and specificity of 38.98% (p < 0.0001). A mild negative correlation is seen between PlGF levels and severity of PIH (p-0.0382). Conclusion: MAP and UAD can be easily incorporated into the infrastructure of most hospitals. If the biochemical test kits are made available at a low cost through available programs such as JSSK, it can bring down the MMR by preventing gestational hypertension. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide. Early detection is crucial for reducing cardiac damage in people with ACS. Prompt risk classification and diagnosis allows for early therapy commencement, reducing the patient's chance of unfavourable outcomes. Cardiac troponins I and T, which have high sensitivity and tissue specificity, are often used to diagnose ACS alongside an electrocardiogram (1). Objectives: 1. Study the analytical competence of PAPP-A in patients admitted to the emergency department with chest pain and finally diagnosed as ACS. 2. Comparison of PAPP-A levels in sub-types of ACS. 3. Comparison of PAPP A and troponin I in subtypes of ACS. Material & Methods: Study Design: Case control study. Study area: The study was conducted in the Department of General Medicine, in a tertiary Care teaching hospital. Study Period: October 2022 to September 2023. Sample Size: A case-control study of 88 subjects divided equally into 2 groups. Study Tools and Data Collection Procedure Specimen Collection: 5 ml venous blood was drawn from all groups within 6 hours of presentation to emergency department, in red capped tubes. Blood was allowed to clot and serum separated thereafter. Hemolysed and lipemic samples were not accepted. Serum was stored in aliquots at -20 °C for estimation of PAPP A and Troponin I. Parameters Estimated: Serum: 1) PAPP A. 2) Troponin I. Results: In this study, the mean serum levels of Troponin-I in UA, NSTEMI and STEMi are 2.306 + 1.83, 11.29 + 7.84, 38.95 + 16.86 respectively. Among 50 patients of acute coronary syndrome, suggesting that Troponin levels are more in STEMI, NSTEMI, UA patients compared to normal controls. Troponin-I levels are significantly higher in blood samples from patients diagnosed with MI. The mean serum PAPP-A levels are 0.113 + 0.3006, 0.294 + 0.393, 1.379 + 1.66 in UA, NSTEMI and STEMI patients whereas mean serum levels of Troponin-I are 2306 + 1.8, 11.29 + 7.849 and 38.95 + 16.86 in UA, NSTEMI and STEMI patients. Conclusion: PAPP-A might be useful as an indicator of inflammation to identify unstable plaque and might, consequently, be an important clinical aid in reducing the incidence of ACS and the disability and mortality associated with this condition. Circulating PAPP-A levels can identify patients early in the process of plaque instability, when it might still be possible to avert myocardial injury. [ABSTRACT FROM AUTHOR]

Objective: We aimed to study the correlation between pregnancy-associated plasma protein-A (PAPP-A) and acute cerebral infarction (ACI). Methods: Patients who had the symptoms of paralysis, aphasia, or sudden neurological impairment from June 2020 to October 2021 were chosen. There were 159 patients diagnosed with ACI as the experimental group and 102 patients without ACI as the control group. We collected clinical data and observed whether they have a certain impact on plasma PAPP-A levels. The ACI group was divided into two groups: mild neurological deficit group (NIHSS score < 3) and moderate and severe neurological deficit group (NIHSS score> 3). The ACI group was divided into the atherosclerotic-type group and the arteriolar occlusion-type group according to the TOAST classification. The ACI group was divided into a good prognosis group (mRS≤2 points) and a poor prognosis group (mRS>2 points) using the Modified Rankin Scale (mRS) for 90 days of follow-up. Plasma PAPP-A levels were compared between those groups. Results: (1) The plasma PAPP-A level in patients with ACI (1.840 ± 0.281) was significantly higher than that in the control group (1.690 + 0.260). Smoking history, leukocyte count, cystatin C, homocysteine, and plasma PAPP-A levels were independently correlated with ACI. (2) The level of PAPP-A in patients with moderate and severe neurological impairment was lower than that in patients with mild neurological impairment. (3) The level of PAPP-A in patients in the arteriolar occlusion-type group was higher than that in patients in the atherosclerosis-type group. (4) The PAPP-A levels in the group with elevated low-density lipoprotein are higher than those in the group with normal low-density lipoprotein. (5) Plasma PAPP-A level was not correlated with infarction location, infarction volume, or prognosis at the 90-day follow-up. Conclusion: (1) The level of plasma PAPP-A could be the independent risk factor of ACI. It is positively correlated with triglyceride and cholesterol content. (2) PAPP-A level is positively correlated with low-density lipoprotein. (3) PAPP-A levels between different disease severities have a significant difference. (4) The level of plasma PAPP-A in the arteriolar occlusion-type group was higher than that in the atherosclerotic-type group. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) regulates cellular lipid content, whereas pregnancy-associated plasma protein-A (PAPP-A) increases IGF-1 bioavailability. Using in vitro-matured cumulus-oocyte complexes, we aimed to evaluate the impact of PAPP-A on the blastocyst lipid content, embryo cryotolerance and embryonic transcriptional profile. We determined that PAPP-A did not affect the lipid content of oocytes, blastocysts, or blastocyst yield (P > 0.05). However, PAPP-A modulated the embryo transcriptional profiles by downregulating PPARGC1A and AKR1B1, which are related to lipid metabolism; CASP9, a pro-apoptotic gene; and IFN-τ, a marker of embryo quality (P < 0.05). Furthermore, the use of PAPP-A improved blastocyst re-expansion in the first 3 h of culture after vitrification (P < 0.05). Although PAPP-A did not affect the blastocyst lipid content or embryo production, we suggest that embryonic transcriptional modulation could contribute to maintain the balance in embryo lipid metabolism. Furthermore, PAPP-A's approach seems to control key intracellular pathways that improve post-cryopreservation development of blastocysts. [ABSTRACT FROM AUTHOR]

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as β-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The pappalysin metalloproteinases, PAPP-A and PAPP-A2, have emerged as highly specific proteolytic enzymes involved in the regulation of insulin-like growth factor (IGF) signaling. The only known pappalysin substrates are a subset of the IGF binding proteins (IGFBPs), which bind IGF-I or IGF-II with high affinity to antagonize receptor binding. Thus, by cleaving IGFBPs, the pappalysins have the potential to increase IGF bioactivity and hence promote IGF signaling. This is relevant both in systemic and local IGF regulation, in normal and several pathophysiological conditions. Stanniocalcin-1 and -2 were recently found to be potent pappalysin inhibitors, thus comprising the missing components of a complete proteolytic system, the stanniocalcin-PAPP-A-IGFBP-IGF axis. Here, we provide the biological context necessary for understanding the properties of this molecular network, and we review biochemical data, animal experiments, clinical data, and genetic data supporting the physiological operation of this branch as an important part of the IGF system. However, although in vivo data clearly illustrate its power, it is a challenge to understand its subtle operation, for example, multiple equilibria and inhibitory kinetics may determine how, where, and when the IGF receptor is stimulated. In addition, literally all of the regulatory proteins have suspected or known activities that are not directly related to IGF signaling. How such activities may integrate with IGF signaling is also important to address in the future. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II. Methods: The twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays. Results: In the twin cohort, PAPP-A increased with age (r=0.19; P<0.05), whereas IGF-I decreased (r=-0.12; P<0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P<0.05) and females (r=0.25; P<0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P<0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P<0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II. Discussion: This twin study confirms our hypothesis that the heritability of PAPPA serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age. [ABSTRACT FROM AUTHOR]

The insulin-like growth factors IGF-I and IGF-II—as well as their binding proteins (IGFBPs), which regulate their bioavailability—are involved in many pathological and physiological processes in cardiac tissue. Pregnancy-associated plasma protein A (PAPP-A) is a metalloprotease that preferentially cleaves IGFBP-4, releasing IGF and activating its biological activity. Previous studies have shown that PAPP-A-specific IGFBP-4 proteolysis is involved in the pathogenesis of cardiovascular diseases, such as ischemia, heart failure, and acute coronary syndrome. However, it remains unclear whether PAPP-A-specific IGFBP-4 proteolysis participates in human normal cardiomyocytes. Here, we report PAPP-A-specific IGFBP-4 proteolysis occurring in human cardiomyocytes derived from two independent induced pluripotent cell lines (hiPSC-CMs), detected both on the cell surface and in the cell secretome. PAPP-A was measured by fluoroimmune analysis (FIA) in a conditioned medium of hiPSC-CMs and was detected in concentrations of up to 4.3 ± 1.33 ng/mL and 3.8 ± 1.1 ng/mL. The level of PAPP-A-specific IGFBP-4 proteolysis was determined as the concentration of NT-IGFBP-4 proteolytic fragments using FIA for a proteolytic neo-epitope-specific assay. We showed that PAPP-A-specific IGFBP-4 proteolysis is IGF-dependent and inhibited by EDTA and 1,10-phenanthroline. Therefore, it may be concluded that PAPP-A-specific IGFBP-4 proteolysis functions in human normal cardiomyocytes, and hiPSC-CMs contain membrane-bound and secreted forms of proteolytically active PAPP-A. [ABSTRACT FROM AUTHOR]

Copyright of Ahi Evran Medical Journal is the property of Ahi Evran University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGβ, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto–placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto–maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 47% of women with an episode of preterm labor deliver at term; however, their infants are at greater risk of being small for gestational age and for neurodevelopmental disorders. In these cases, a pathologic insult may disrupt the homeostatic responses sustaining pregnancy. We tested the hypothesis of an involvement of components of the insulin-like growth factor (IGF) system. Methods: This is a cross-sectional study in which maternal plasma concentrations of pregnancy-associated plasma protease (PAPP)-A, PAPP-A2, insulin-like growth factor-binding protein 1 (IGFBP-1), and IGFBP-4 were determined in the following groups of women: (1) no episodes of preterm labor, term delivery (controls, n = 100); (2) episode of preterm labor, term delivery (n = 50); (3) episode of preterm labor, preterm delivery (n = 100); (4) pregnant women at term not in labor (n = 61); and (5) pregnant women at term in labor (n = 61). Pairwise differences in maternal plasma concentrations of PAPP-A, PAPP-A2, IGFBP-1, and IGFBP-4 among study groups were assessed by fitting linear models on log-transformed data and included adjustment for relevant covariates. Significance of the group coefficient in the linear models was assessed via t-scores, with p < 0.05 deemed a significant result. Results: Compared to controls, (1) women with an episode of premature labor, regardless of a preterm or a term delivery, had higher mean plasma concentrations of PAPP-A2 and IGFBP-1 (each p < 0.05); (2) women with an episode of premature labor who delivered at term also had a higher mean concentration of PAPP-A (p < 0.05); and (3) acute histologic chorioamnionitis and spontaneous labor at term were not associated with significant changes in these analytes. Conclusion: An episode of preterm labor involves the IGF system, supporting the view that the premature activation of parturition is a pathologic state, even in those women who delivered at term. [ABSTRACT FROM AUTHOR]

Copyright of Jinekoloji-Obstetrik & Neonatoloji Tip Dergisi is the property of T.C. Saglik Bakanligi Ankara Sehir Hastanesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To investigate the association of vaginal birth complications with first trimester pregnancy associated plasma protein A (PaPP-A) level in LGA vaginal deliveries of non-diabetic mothers. Methods: This is a retrospective study conducted in a tertiary hospital between May 2020 and July 2022. A total of 9,184 singleton pregnancies with normal vaginal delivery between 37 and 42 weeks were reviewed. Non-diabetic patients who gave birth to LGA infants were grouped according to the presence of vaginal birth complications and compared in terms of first trimester aneuploidy screening results. Regression analysis was used to investigate the effect of variables on complications. Receiver operating characteristic (ROC) analysis was performed for the threshold PaPP-A value to predict birth complications. Results: Of the 357 patients, 68 (19.0%) had at least one complication, remaining 289 (81.0%) had no complications. First trimester serum PaPP-A level was significantly higher in complicated group than patients without complications (20.85 ± 19.73 vs 15.18 ± 15.81, p= 0.046). First trimester NT, β-hCG and PaPP-A are significantly associated with perinatal complications in LGA vaginal deliveries. The cut-off value of first trimester PaPP-A level was 10.46 mIU/mL to predict the complications with a sensitivity of 54.4% and a specificity of 54.3%. Conclusions: First trimester PaPP-A level may be associated with vaginal birth complications in LGA infants from non-diabetic mothers. [ABSTRACT FROM AUTHOR]

To determine whether preimplantation genetic testing (PGT) is associated with a change in maternal serum analyte levels in pregnancies conceived via in vitro fertilization (IVF). Retrospective cohort of singleton and twin IVF pregnancies with available first- or second-trimester serum analyte data from 01/2014 to 09/2019. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol, were compared between two groups: pregnancies conceived after transfer of PGT screened euploid embryos vs. those conceived after transfer of untested embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Nine hundred and sixty-two singleton and 165 twin IVF pregnancies with serum analyte data available for analysis were included. PGT was associated with a higher median first- and second-trimester AFP compared to no PGT in singletons (1.23 MoM vs. 1.13 MoM; parameter estimate [PE] 1.08, 95% CI 1.00–1.17, p=.04, and 1.21 MoM vs. 1.07 MoM; PE 1.07, 95% CI 1.01–1.13, p=.01, respectively). PGT was also associated with a lower median PAPP-A compared to no PGT in twins (0.75 MoM vs. 1.18 MoM, PE 0.74, 95% CI 0.60–0.92, p=.006). Our data suggest that PGT is associated with higher maternal serum levels of second-trimester AFP in singleton and lower levels of first-trimester PAPP-A in twin pregnancies conceived via IVF. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers. Methods: This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) – 143 patients; group B (ART/no PGT-A/FET) – 100 patients; group C (ART/no PGT-A/fresh ET) – 346 patients, and group D (NC) – 139 patients. Results: Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPPA) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups (p = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/ PGT-A/FET group versus ART/no PGT-A/FET group (p = .01) and NC versus ART/no PGT-A/FET (p = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET (p = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (b-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free b-hCG among the compared groups (p = .5789) and when subgroup analysis was performed (p>.05). The normality of the distribution of variables was analyzed by the Kolmogorov–Smirnov test and the median PAPP-A and free bhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA. Conclusions: Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: With the increasing prevalence of liver steatosis, non-invasive methods are sought to detect it and to assess the degree of lipid accumulation in the liver. The aim of this preliminary study was to assess the serum concentrations of stanniocalcin-2 (STC-2), pregnancy-associated plasma protein A (PAPP-A) and insulin-like growth factor binding protein (IGFBP-4) among children with obesity, check if they detect liver steatosis and determine whether they differentiate mild and advanced steatosis. Material and methods: This prospective study involved 62 obese children (39 boys and 23 girls, median age 13.75 years). Infectious, autoimmune, metabolic and toxic liver conditions were excluded. All subjects underwent body composition analysis, anthropometric measurements, abdominal ultrasound and routine blood chemistry analyses. STC-2, PAPPA and IGFBP-4 were measured using ELISA kits. The control group consisted of 19 non-obese, healthy children with correct body mass index and without organic pathologies. Results: The concentration of examined biomarkers in obese children with liver steatosis was significantly higher than in the control group and STC-2 was also significantly higher in children with advanced steatosis in comparison to children with mild steatosis. In the group of obese children with liver steatosis STC-2 positively correlated with: gamma-glutamyltransferase, cholesterol, triglycerides, low-density lipoprotein cholesterol, homeostatic model assessment-insulin resistance and waist-hip ratio. The ability of serum STC-2 to detect advanced liver steatosis was significant (AUC = 0.746, p = 0.0022, cut-off 135.27 pg/ml). Conclusions: This preliminary study demonstrated that STC-2 can be regarded as a potential non-invasive marker of advanced liver steatosis in obese children. The other analyzed parameters (PAPP-A and IGFBP-4) seem not to be useful in diagnosis of liver steatosis in obese children. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the potential of pregnancy-associated plasma protein A (PAPP-A) and clinical data in predicting gestational diabetes mellitus (GDM). Clinical data of 318 pregnant women with GDM and 200 healthy pregnant women were retrospectively analysed. The age, BMI and caesarean section in GDM were significantly higher than in normal group. Serum and placental levels of PAPP-A were significantly lower in GDM than in normal group. Pearson's correlation analysis showed that serum levels of PAPP-A were negatively correlated with BMI and blood glucose level. Binary logistic regression analysis displayed that PAPP-A were the potential factors influencing GDM. The area under the ROC curve (AUC) for PAPP-A combined with BMI in predicting GDM was 0.941, significantly higher than that of the single one. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What is already known on this subject? GDM not only increases the risk of perinatal morbidity, but also results in an increased risk of long-term sequelae for both mother and child including diabetes, cardiovascular disease obesity. Previous data indicate that besides glycemic control in the second trimester, interventions initiated early in pregnancy can reduce the rate of GDM in pregnant women. The expression of PAPP-A in serum of GDM pregnant women was decreased in the first trimester. Whereas, whether PAPP-A can be as an early predictor of GDM is not clear. What do the results of this study add? The present study shows that PAPP-A MoM was less than 0.6757 in the first trimester of pregnancy is more prone to GDM. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What are the implications of these findings for clinical practice and/or further research? Early GDM prediction is crucial for prevention and management of GDM, to cope with the rising prevalence of GDM and reduce later life chronic disease of both mother and child. Based on the level of PAPP-A MoM and BMI, interventions such as lifestyle changes initiated early in pregnancy shouldbeenabledin pregnant women. [ABSTRACT FROM AUTHOR]

Copyright of Medical Journal of Istanbul Kanuni Sultan Süleyman / İstanbul Kanuni Sultan Süleyman Tıp Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Coronavirus-19 is still considered a pandemic that influences the world. Other molecular alterations should be clearer besides the increasing cytokine storm and pro-inflammatory molecules. Hypoxic conditions that induce HIF-1α lead to stimulate gene expression of STC-2 that targets PAPP-A expression. This study aimed to determine gene expression levels of PAPP-A, STC-2, and HIF-1α in COVID-19 infection. We also aimed to reveal the relationship of these genes with laboratory and clinical data of COVID-19 patients. Materials and Results: We extracted RNA from peripheral blood samples of COVID-19(+) and COVID-19(−) individuals. The real-time PCR method was used to measure mRNA expression of PAPP-A, STC-2, and HIF-1α. Gene expression analysis was evaluated by the 2−ΔΔCt method. PAPP-A, STC-2, and HIF-1α mRNA expressions of severe patients were higher than healthy individuals (p = 0.0451, p = 0.4466, p < 0.0001, respectively). Correlation analysis of gene expression patterns of severe patients demonstrated a positive correlation between PAPP-A and STC-2 (p < 0.0001, r = 0.8638). Conclusion: This is the first study that investigates the relation of PAPP-A, STC-2, and HIF-1α gene expression in patients with COVID-19 infection. Besides the routine laboratory findings, PAPP-A, STC-2, and HIF-1α mRNA expressions may be considered to patients' prognosis as a sign of increased cytokines and pro-inflammatory molecules. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prediction performance of serum placental growth factor (PLGF), free human chorionic gonadotropin β (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels in early pregnancy for pregnancy outcomes. Methods: A total of 4256 pregnant women who underwent obstetric examinations in our hospital from June 2018 to June 2020 and completed their full pregnancy were included in the study. The clinical pregnancy outcomes of pregnant women with different PLGF, PAPP-A and β-hCG levels in early pregnancy were recorded, and the prediction performance of the above indicators for adverse pregnancy outcomes was discussed. Results: Pregnant women with increased or decreased PLGF or increased PAPP-A or β-hCG had significantly higher incidence of adverse pregnancy outcomes than normal pregnant women. Pregnant women with abnormal pregnancy had significantly higher β-hCG and PLGF, and lower PAPP-A than those with normal pregnancy. The sensitivity of serum PLGF, β-hCG and PAPP-A in early pregnancy for predicting adverse pregnancy outcomes was 95.13%, 94.19% and 97.75%, and the specificity was 84.31%, 85.80% and 83.22%, respectively. Conclusions: Serum PLGF, PAPP-A and β-hCG in early pregnancy are more effective in predicting adverse pregnancy outcomes. Clinical monitoring of patients with increased PLGF, decreased PAPP-A, and increased β-hCG should be strengthened, especially the monitoring of antepartum examination and B-ultrasound detection of pregnant women with abnormal indicators in middle and late pregnancy, so as to identify adverse pregnancy outcomes as early as possible and give targeted intervention. [ABSTRACT FROM AUTHOR]

The use of the second trimester alpha-fetoprotein (AFP) along with the first trimester pregnancy-associated plasma protein-A (PAPP-A) has been found to be useful in the estimation of unfavourable pregnancy outcome. Our aim in this study was to determine the relationship between maternal PAPP-A and b-hCG and AFP concentrations in spontaneous preterm birth (sPTB). This prospective cohort study included 372 singleton pregnancies with PAPP-A, b-hCG and AFP levels in the first trimester, which were converted to multiples of the median (MoM). The predictive ability of AFP-to-PAPP-A and AFP-to-b-hCG ratios for sPTB was evaluated. The risk for sPTB ≤34 weeks increased in women with AFP-to-PAPP-A ratio >7 (OR 2.9, 95% CI 1.2–6.4). Women with AFP-to-b-hCG ratio >0.6 had a 3.5-fold higher risk for sPTB ≤32 weeks. Increased maternal AFP-to-PAPP-A or AFP-to-b-hCG ratios in the first trimester may help to predict pregnant women at high risk for sPTB, and this may be beneficial in developing management plans. What is already known on this subject? There is a synergistic association between the combination of low pregnancy-associated plasma protein-A (PAPP-A) in the first trimester with alpha-fetoprotein (AFP) in the second trimester with subsequent development of PTB. Maternal serum biochemical markers measured as a part of aneuploidy screening are reflective of pregnancy adverse outcomes related with placental insufficiency. PAPP-A and AFP have a low predictive ability to determine women at high risk for preterm birth. What do the results of this study add? Elevated AFP:PAPP-A or AFP:B-HCG ratio in the first trimester is associated with increased risk for sPTB. The ratios of these biochemical markers in the first trimester may be beneficial to identify women at high risk for sPTB. What are the implications of these findings for clinical practice and/or further research? The ratios may predict pregnant women at high risk for sPTB, and such risk may be helpful in the development of a management plan. Incorporation of AFP:PAPP-A or AFP:B-HCG ratios in the first trimester may help to improve the screening efficacies, and provide a simple alternative tool. [ABSTRACT FROM AUTHOR]

Objective: To assess whether pregnancy-associated plasma protein-A (PAPP-A) alters or provides equivalent screening performance as placental growth factor (PlGF) when screening for preterm pre-eclampsia (PE) at 11-13 weeks of gestation.Methods: This was a secondary analysis of a non-intervention screening study of 6546 singleton pregnancies that were screened prospectively for preterm PE in the first trimester between December 2016 and June 2018. Patient-specific risks for preterm PE were estimated by maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF and PAPP-A. A competing-risks model with biomarkers expressed as multiples of the median was used. All women and clinicians were blinded to the risk for preterm PE. The performance of screening for preterm PE using PlGF vs PAPP-A vs both PAPP-A and PlGF was assessed by comparing areas under the receiver-operating-characteristics (AUC) curves. McNemar's test was used to compare detection rate at a fixed false-positive rate (FPR) of 10%.Results: PlGF and PAPP-A were measured in 6546 women, of whom 37 developed preterm PE. The AUC and detection rate at 10% FPR using PlGF in combination with maternal history, MAP and UtA-PI were 0.854 and 59.46%, respectively. The respective values were 0.813 and 51.35% when replacing PlGF with PAPP-A and 0.855 and 59.46% when using both PAPP-A and PlGF. Statistically non-significant differences were noted in AUC when replacing PlGF with PAPP-A (ΔAUC, 0.04; P = 0.095) and when using both PAPP-A and PlGF (ΔAUC, 0.002; P = 0.423). However, on an individual case basis, screening using PlGF in conjunction with maternal history, MAP and UtA-PI identified three (8.1%) additional pregnancies that developed preterm PE and that were not identified when replacing PlGF with PAPP-A. Screening using PAPP-A in addition to maternal history and other biomarkers did not identify any additional pregnancies.Conclusion: On an individual case basis, adoption of a screening strategy that uses PAPP-A instead of PlGF results in reduced detection of preterm PE, consistent with previous literature. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB.Methods: This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs).Results: A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively.Conclusions: We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Copyright of Jinekoloji-Obstetrik & Neonatoloji Tip Dergisi is the property of T.C. Saglik Bakanligi Ankara Sehir Hastanesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. The universal screening for GDM is usually performed between 24-28 weeks' gestation. This often delays the diagnosis and could increase the risk of adverse pregnancy outcomes. Some of the biochemical placental markers -- pregnancy associated plasma protein A (PAPP-A) and free-ß human chorionic gonadotropin (hCG), probably could provide a diagnostic value for GDM. The aim of our study was to assess if PAPP-A and hCG values were different among pregnant women with and without GDM and respectively, to tested their place in the early GDM screening. Material and methods: We conducted a retrospective, case-control study by reviewing the clinical database records of 662 pregnant women. The analysis includes the data for a two-year period. The patients included in the observation were divided into two groups -- GDM group (n = 412) and Euglycemic group (n = 250). Early screening for GDM between 9-12 weeks' gestation was performed in 173 of the women in the interventional group due to: registered fasting plasma glucose (FPG) above 5.1 mmol/L, obesity, macrosomia in previous pregnancies or family history for diabetes mellitus. The remaining 239 women underwent universal screening at 24-28 weeks' gestation. Mean serum levels of PAPP-A, hCG, FPG, and body mass index (BMI) were measured between 10-13 gestational weeks. Serum levels of PAPP-A and hCG are presented as multiples of the normal median (MoM), adjusted by maternal baseline characteristics and demographics. Results: In patients who developed GDM during pregnancy, compared with the control group, we have found significantly lower MoM values of PAPP-A (p < 0.0001), higher levels of FPG (p < 0.0001) and higher BMI (p < 0.0001). Median hCG MoM was similar in both group of pregnant women. Conclusions: Our findings suggest that low-normal to low reference range values of PAPP-A might be associated with higher risk for GDM. PAAP-A levels can be used as an additional factor to recommend early screening for GDM. [ABSTRACT FROM AUTHOR]

Objectives: The present study was designed to evaluate and compare the screening markers of spontaneous and in vitro fertilization (IVF) pregnancies in individuals who underwent combined screening in the first trimester of pregnancy. Materials and Methods: In this retrospective study, we examined the difference between natural and assisted-reproductive technology (ART) pregnancies in 2252 mothers from January 2011 to October 2019. In both groups, the first trimester screening parameters including NT, free beta-human chorionic gonadotropin (ß-hCG), and PAPP-A were measured. Results: According to the results of the present study, BMI was higher in the group that became pregnant by IVF compared to the normal pregnancy group (P < 0.001). Additionally, in patients using IVF, the history of maternal disease was less frequent compared to the other group (P = 0.003). Most cases of twin fetuses, dichorionic twin pregnancy, and fetal abnormality were seen in the IVF group. Although the ß-hCG and free PAPP-A levels were high in the IVF group, no significant difference was observed. The group with spontaneous pregnancy had a higher penetration rate of nuchal translucency <95th percentile compared to the IVF group (P < 0.001). The results of comparing the first trimester test showed that in the IVF group, 81.3% of patients were at low risk and 6.6% were at high risk, while in the normal pregnancy group, 78.9% of patients were at low risk and 7.0% of them were at low risk, indicating that the difference was not significant. Conclusions: Overall, although the risk of aneuploidy in IVF pregnancies was not higher compared to normal pregnancies, in IVF pregnancies, NI is associated with a high risk of fetal abnormalities. Therefore, NT sonography can help to diagnose fetal anomalies especially aneuploidy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of using progesterone due to early vaginal bleeding on aneuploidy screening markers in the first trimester.Material and Methods: This case control study includes the pregnant women who applied to our clinic in order to have a screening test for Down syndrome in the weeks of 11°/7-136/7. The patients were divided into three groups. Self reported vaginal bleeding with progesterone therapy (Bl+, Prg+, n:70), Self reported vaginal bleeding without progesterone therapy (Bl+, Prg-, n:70) and as a control group pregnant women who had no vaginal bleeding. (NoBl, NoPrg, n:70). In all patients, free beta-human chorionic gonadotrophin (β-hCG), pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency (NT) thickness were analyzed. Mean MoMs of the markers were compared between three groups.Results: In the two groups with vaginal bleeding (Bl+, Prg + and Bl+, Prg-) the free β-Hcg MoM values were statistically higher (1.22 ± 0.72, 0.98 ± 0.45, respectively) compared to the No Bleeding/No Progesterone group (0.81 ± 0.52) (p ≤ 0.001, p ≤ .01, respectively). However, no significant difference was found between the free β-hCG MoM value of women with Bl+, Prg + group (1.22 ± 0.72) and Bl+, Prg - group (0.98 ± 0.45). (p: .053, significance level limitation with Bonferroni correction p: .017). PAPP-A and NT thickness did not differ significantly between the groups.Conclusion: Our data did not find an association between the use of oral progesterone and any alternations in first trimester screening parameters. Regardless of the progesterone usage, vaginal bleeding in the first trimester pregnancies increased the free β-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nuchal translucency (NT) is an important finding of early fetal anatomy scan because of the association with genetic and structural anomalies. Enlarged nuchal translucency can be easily detected even without measurement on fetal anatomy scan as a neck pathology. Because of demanding criteria for measurning NT in established prenatal aneuploidy screening we came with an idea of improvement and simplification with availabe methods. The aim of this study is to compare established screening methods with new model of screening composed of fetal anatomy scan with integrated nuchal translucency and combination of PAPP-A and fβhCG. METHODS: A prospective one center study analyzed a total of 351 pregnancies between January 2017 and December 2020. Sonographic measurement of NT and fetal anatomy scan (FAS) were performend with biochemical testing from blood sample in the first trimester. Combined screening and fetal anatomy scan was performed. Patients with a pathological screening or with structural defects underwent an invasive procedure. In patient with positive screenining who missed the first trimester invasive procedure, amniocentesis was performed. Fetuses were divided into two groups according to positive or negative karyotype and to calculate sensitivity and specificity of screening methods. From statistical methods regression analysis, significance p of individual predictor, sensitivity and specificity with graphic drawing of ROC charts were used. Data were analyzed using statistical tools of Microsoft Excel 365 and BESH stat. RESULTS: Four models for aneuploidy screening were tested. 1) Model of „Age at the time of diagnosis" was slightly significant predictor with insignificant odds ratio (P=0.04, OR=1). 2) Model of„ First trimester biochemical screening" (age, free beta human chorionic gonadotropine -- fβhCG and pregnancy associated plasmatic protein A -- PAPP-A) were significant (P=0.0001; LR=21) with sensitivity of 87.5 % and specificity of 65.7 %. 3) Model of „First trimester combined test“ (age of patients at the time of diagnosis, fβhCG, PAPP-A, NT) was significant (P=7.9 x10-14, LR=67, sensitivity 87 %, specificity 80 %). 4) Model of „Fetal anatomy scan with biochemistry" (structural abnormality finding with combination including age, fβhCG and PAPP-A) was significant (P=4.9x10-18, LR=87, sensitivity 95 %, specificity 80 %). CONCLUSION: Fetal anatomy scan combined with age, fβhCG and PAPP-A has the highest sensitivity and specificity for both, the detection of fetal aneuploidies and structural abnormalities. Our study shows that fetal anatomy scan is the best possible option for first trimester diagnostics (Tab. 4, Fig. 5, Ref. 16). Text in PDF www.elis. sk [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few effective treatment options. We found a highly significant correlation between pregnancy‐associated plasma protein (PAPP)‐A expression in IPF lung tissue and disease severity as measured by various pulmonary and physical function tests. PAPP‐A is a metalloproteinase that enhances local insulin‐like growth factor (IGF) activity. We used primary cultures of normal adult human lung fibroblasts (NHLF) to test the hypothesis that PAPP‐A plays an important role in the development of pulmonary fibrosis. Treatment of NHLF with pro‐fibrotic transforming growth factor (TGF)‐β stimulated marked increases in IGF‐I mRNA expression (>20‐fold) and measurable IGF‐I levels in 72‐h conditioned medium (CM). TGF‐β treatment also increased PAPP‐A levels in CM fourfold (p = 0.004) and proteolytic activity ~2‐fold. There was an indirect effect of TGF‐β to stimulate signaling through the PI3K/Akt pathway, which was significantly inhibited by both IGF‐I‐inactivating and PAPP‐A inhibitory antibodies. Induction of senescence in NHLF increased PAPP‐A levels in CM 10‐fold (p = 0.006) with attendant increased proteolytic activity. Thus, PAPP‐A is a novel component of the senescent lung fibroblast secretome. In addition, NHLF secreted extracellular vehicles (EVs) with surface‐bound active PAPP‐A that were increased fivefold with senescence. Regulation of PAPP‐A and IGF signaling by TGF‐β and cell senescence suggests an interactive cellular mechanism underlying the resistance to apoptosis and the progression of fibrosis in IPF. Furthermore, PAPP‐A‐associated EVs may be a means of pro‐fibrotic, pro‐senescent communication with other cells in the lung and, thus, a potential therapeutic target for IPF. [ABSTRACT FROM AUTHOR]

To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM). It was a retrospective cohort study. Study groups were presented: type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week's gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated. The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51–1.1), and type 2 DM-0.88 (IQR, 0.42–1.15) compared to the unaffected group 1.03 (IQR, 0.96–1.12; p =.025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p =.14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5–10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth. The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine if pregnancy-associated plasma protein-A (PAPP-A), typically measured in maternal serum and a potential predictor of adverse maternal and fetal outcomes such as spontaneous miscarriage, pre-eclampsia, and stillbirth, is expressed in blastocoel fluid–conditioned media (BFCM) at the embryonic blastocyst stage. Design: This is an in vitro study. Methods: BFCM samples from trophectoderm-tested euploid blastocysts (n = 80) from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were analyzed for PAPP-A mRNA. BFCM was obtained from blastocyst stage embryos in 20 uL drops. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy prior to blastocyst vitrification and BFCM collection for snap freezing. cfDNA was synthesized using BFCM collected from 80 individual euploid blastocysts. Next, real-time qPCR was performed to detect expression of PAPP-A with GAPDH for normalization of expression in each sample. Results: PAPP-A mRNA was detected in 45 of 80 BFCM samples (56.3%), with varying levels of expression across samples. Conclusion: Our study demonstrates the expression of PAPP-A in BFCM. To our knowledge, this is the first study to report detection of PAPP-A mRNA in BFCM. Further studies are required and underway to investigate a greater number of BFCM samples as well as the possible correlation of PAPP-A expression with pregnancy outcomes of transferred euploid blastocysts. If found to predict IVF and obstetric outcomes, PAPP-A may provide additional information along with embryonic euploidy for the selection of the optimal blastocyst for embryo transfer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome.Methods: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA).Results: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile.Conclusions: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are among the leading causes of death and disability worldwide. Pregnancy-associated plasma protein-A (PAPP-A) is a matrix metalloprotease localized on the cell surface. One of the substrates that PAPP-A cleaves is the insulin-like growth factor binding protein-4 (IGFBP-4), a member of the family of proteins that bind insulin-like growth factor (IGF). Proteolysis of IGFBP-4 by PAPP-A occurs at a specific site resulting in formation of two proteolytic fragments – N-terminal IGFBP-4 (NT-IGFBP-4) and C-terminal IGFBP-4 (CT-IGFBP-4), and leads to the release of IGF activating various cellular processes including migration, proliferation, and cell growth. Increased levels of the proteolytic IGFBP-4 fragments correlate with the development of CVD complications and increased risk of death in patients with the coronary heart disease, acute coronary syndrome, and heart failure. However, there is no direct evidence that PAPP-A specifically cleaves IGFBP-4 in the cardiac tissue under normal and pathological conditions. In the present study, using a primary culture of rat neonatal cardiomyocytes as a model, we have demonstrated that: 1) proteolysis of IGFBP-4 by PAPP-A occurs in the conditioned medium of cardiomyocytes, 2) PAPP-A-specific IGFBP-4 proteolysis is increased when cardiomyocytes are transformed to a hypertrophic state. Thus, it can be assumed that the enhancement of IGFBP-4 cleavage by PAPP-A and hypertrophic changes in cardiomyocytes accompanying CVD are interrelated, and PAPP-A appears to be one of the activators of the IGF-dependent processes in normal and hypertrophic-state cardiomyocytes. [ABSTRACT FROM AUTHOR]

Objective: To compare the screening performance of serum pregnancy‐associated plasma protein‐A (PAPP‐A) vs placental growth factor (PlGF) in routine first‐trimester combined screening for pre‐eclampsia (PE), small‐for‐gestational age (SGA) at birth and trisomy 21. Methods: This was a retrospective study nested in pregnancy cohorts undergoing first‐trimester combined screening for PE and trisomy 21 using The Fetal Medicine Foundation (FMF) algorithm based on maternal characteristics, nuchal translucency thickness, PAPP‐A, free beta‐human chorionic gonadotropin, blood pressure and uterine artery Doppler. Women at high risk for preterm PE (≥ 1 in 50) received 150 mg of aspirin per day, underwent serial fetal growth scans at 28 and 36 weeks and were offered elective birth from 40 weeks of gestation. PlGF was quantified retrospectively from stored surplus first‐trimester serum samples. The performance of combined first‐trimester screening for PE and SGA using maternal history, blood pressure, uterine artery pulsatility index and either PAPP‐A or PlGF was calculated. Similarly, the performance of combined first‐trimester screening for trisomy 21 was calculated using either PAPP‐A or PlGF in addition to maternal age, nuchal translucency thickness and free beta‐human chorionic gonadotropin. Results: Maternal serum PAPP‐A was assayed in 1094 women, including 82 with PE, 111 with SGA (birth weight < 10th centile), 53 with both PE and SGA and 94 with fetal trisomy 21. PlGF levels were obtained retrospectively from 1066/1094 women. Median serum PlGF multiples of the median was significantly lower in pregnancies with PE (1.0 (interquartile range (IQR), 0.8–1.4); P < 0.01), SGA (1.0 (IQR, 0.8–1.3); P < 0.001) and trisomy 21 (0.6 (IQR, 0.5–0.9); P < 0.0001) compared to in controls (1.2 (IQR, 0.9–1.5)). There was no significant difference in the performance of first‐trimester screening using PAPP‐A vs PlGF for either preterm PE (area under the receiver‐operating‐characteristics curve (AUC), 0.78 vs 0.79; P = 0.55) or term PE (AUC, 0.74 vs 0.74; P = 0.60). These findings persisted even after correction for the effect of targeted aspirin use on the prevalence of PE. Similarly, there were no significant differences in sensitivity and specificity of combined screening for SGA or trisomy 21 when using PAPP‐A vs PlGF. Conclusions: Using either PlGF or PAPP‐A in routine first‐trimester combined screening based on maternal characteristics, blood pressure and uterine artery Doppler does not make a significant clinical difference to the detection of PE or SGA. Depending on the setting, biomarkers should be chosen to achieve a good compromise between performance and measurement requirements. This pragmatic clinical‐effectiveness study suggests that combined screening for PE can be implemented successfully in a public healthcare setting without changing current protocols for the assessment of PAPP‐A in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

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Copyright of Perinatal Journal / Perinatoloji Dergisi is the property of Deomed Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To investigate if there is an association between pregnancy complications and abnormal maternal serum analytes used for first trimester screening (FTS) and second trimester screening (STS) for aneuploidy. More than two hundred three pregnant women who had FTS or STS for Down's syndrome who presented between July 2009 and January 2010 were included. First trimester maternal levels of PAPP-A and free hCG or 2nd trimester maternal levels of AFP, uE3 and hCG were compared between healthy pregnancies and those with preeclampsia, intrauterine growth retardation, intrauterine fetal death or oligohydramnios. PAPP-A levels less than 0.4 MoMs were related with elevated preeclampsia and fetal growth retardation risk. AFP levels over 2.5 MoMs were related with all adverse outcomes evaluated in the study including preeclampsia, fetal growth retardation, intrauterine fetal demise and oligohydramnios. While uE3 levels below 0.5 MoM were found to be related with higher preeclampsia incidence, elevated 2nd trimester hCG levels over 3.0 MoMs were associated with fetal growth retardation. No significant relationship could be established between low 1st trimester free hCG levels (less than 0.5 MoMs) and any of the adverse outcomes. First and 2nd trimester serum analytes for Down syndrome screening are significantly linked with pregnancy complications. However, because their sensitivity and positive predictive values are low, these analytes are not shown to be effective in the screening of pregnancy complications when used alone. [ABSTRACT FROM AUTHOR]