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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: Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients. Methods: We obtained carotid (n = 9) and femoral (n = 11) atherosclerotic plaques from patients undergoing vascular surgery and incubated freshly harvested plaque tissue in culture media for 24 h. Subsequently, conditioned media were assayed for PAPP-A, STC2, IGFBP4, and IGF1 using immunoassays. Enzymatic activity of PAPP-A was assessed by its ability to process recombinant IGFBP4-IGF1 complexes - a specific substrate of PAPP-A - by Western blotting. Results: PAPP-A and STC2 were detectable in conditioned media from both carotid and femoral plaques, with higher STC2 concentrations in eluates from carotid plaque incubations (p = 0.02). IGFBP4 and IGF1 were undetectable. Conditioned media from all 20 plaques exhibited PAPP-A proteolytic activity. However, no correlation between PAPP-A concentration and its proteolytic activity was observed, whereas the PAPP-A: STC2 molar ratio correlated with PAPP-A activity (R2 = 0.25, p = 0.03). Conclusion: This study provides evidence for the presence of enzymatically active PAPP-A in atherosclerotic plaques and underscores the need for further investigating potential beneficial effects associated with targeting PAPP-A in atherosclerotic cardiovascular disease.

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]

Objectives. The evaluation of maternal biomarkers that can guide us towards an early diagnosis of gestational diabetes, as early as the first trimester of pregnancy, for a better management and to reduce potential adverse effects of gestational diabetes on pregnancy and pregnant women. Methodology. This article reviews research in the specialized literature and aims to highlight how biomarkers, such as fasting glucose, HOMA score, glycated hemoglobin and PAPP-A, can constitute a set of parameters for screening gestational diabetes as early as the first trimester of pregnancy. Results. Women who developed gestational diabetes exhibited higher values of biomarkers compared to patients unaffected by this metabolic imbalance. Diagnosing gestational diabetes in the first trimester of pregnancy requires correlating multiple biological markers. Most studies suggest that none of the markers used alone have a sufficiently high predictive value for screening gestational diabetes in the first trimester. However, their correlation can quantify the risk of developing this condition and provide a clinical clue in routine practice. [ABSTRACT FROM AUTHOR]

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]

Objectives: In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility. Design: and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4–14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses. Results: During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p

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]

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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]

Purpose: We aimed to compare the current median values of hormone levels used in screening tests performed during the first trimester in pregnant women in Şırnak with the medians of standard software used in hormone devices and to reveal the differences between them. Materials and Methods: In the study, the data of 301 pregnant women who applied to the hospital in Şırnak province between 01/05/2021 and 01/05/2022 were used by pulling prenatal dual screening test measurements from the hospital database after the hospital permission and ethics committee approval were obtained. The MoM levels found according to the median values calculated by the device software and the multiples of the medians (MoM) calculated according to the weekly median levels entered in the program were compared. Results: Current median levels of free β-HCG were found to be statistically significantly different and lower than those used in screening tests at 11, 12, and 13 weeks of gestation (p

OBJECTIVE: Our work aims to determine whether there is an association between first-trimester serum pregnancy-associated plasma protein A (PAPP-A) multiples of the median (MoM) value and placenta previa with or without placenta accreta spectrum disorders (PAS) in women. PATIENTS AND METHODS: A retrospective analysis was performed on 267 patients who had first-trimester screening test results for aneuploidy, including nonadherent placenta previa (n=106), placenta previa with PAS (n=60), and control group (healthy pregnant women with previous cesarean section and normal placental location, n=101). To assess the significant difference between these groups, PAPP-A MoMs were compared. RESULTS: The median PAPP-A MoM of 1.96 in placenta previa with PAS was significant (>0.88) in nonadherent placenta previa and 0.89 in the control group (p<0.001). Serum PAPP-A was found to be significantly associated with the severity of bleeding, such that patients with severe bleeding of 1,500 mL or more (n=54) had a higher mean PAPP-A MoM (1.93±0.69; p<0.001). Furthermore, the mean PAPP-A MoM was found to be 1.96±0.74 in the hysterectomy group and 0.89±0.47 in the conservative management group, and the difference was found to be significantly higher (p<0.001). CONCLUSIONS: Elevated PAPP-A values in the first trimester of pregnancy may be a useful marker for identifying women at higher risk of PAS and adverse outcomes. [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]

Objective: To explore the value of uterine arterial blood flow parameters combined with serum placental growth factor (PLGF) and pregnancy associated plasma protein-A (PAPP-A) in predicting the pregnancy outcome of pregnant women with unexplained recurrent spontaneous abortion (URSA) during early pregnancy. Methods : 103 pregnant women with URSA history who were admitted to our hospital from October 2021 to October 2022 were selected. Their pregnancy outcome at 28 weeks were tracked, and they were divided into normal pregnancy group (n=26) and abortion group (n=77) according to different pregnancy outcome. The uterine artery blood flow parameters [resistance index (RI), pulsation index (PI), peak systolic flow velocity/end-diastolic flow velocity (S/D)] and serum PLGF and PAPP-A levels were compared in the two groups. Multivariate Logistic regression model was used to analyze the influencing factors of pregnancy outcome of pregnant women with URSA during early pregnancy. The predictive value of uterine artery blood flow parameters combined with serum PLGF and PAPP-A for pregnancy outcome of pregnant women with URSA during early pregnancy was analyzed by receiver operating characteristic (ROC) curve. Results: The PI, RI and S/D in the abortion group were significantly higher than those in the normal pregnancy group (P＜0.05), while serum PLGF and PAPP-A levels were significantly lower than those in the normal pregnancy group (P＜0.05). Logistic regression model showed that the elevated PI, RI and S/D were the risk factor for pregnancy outcome of pregnant women with URSA during early pregnancy (P＜0.05), while the elevated serum PLGF and PAPP-A levels were the protective factor (P＜0.05). ROC analysis results showed that the combination of PI, RI, S/D, PLGF, and PAPP-A had the highest efficacy in predicting the pregnancy outcome of pregnant women with URSA during early pregnancy, and the area under the curve (AUC) of combined diagnosis was 0.913, which was significantly better than the diagnosis of each index alone. Conclusion: Uterine arterial blood flow parameters combined with serum PLGF and PAPP-A have high value in predicting pregnancy outcome of pregnant women with URSA during early pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Physiologically, pregnancy-associated plasma protein-A (PAPP-A) serves to liberate bound IGF1 by enzymatic cleavage of IGF-binding proteins (IGFBPs), IGFBP4 in particular. Clinically, PAPP-A has been linked to cardiovascular disease (CVD). Stanniocalcin-2 (STC2) is a natural inhibitor of PAPP-A enzymatic activity, but its association with CVD is unsettled. Therefore, we examined associations between the STC2–PAPP-A–IGFBP4–IGF1 axis and allcause mortality and CVD in patients with type 2 diabetes (T2D). Design: We followed 1284 participants with T2D from the ADDITION trial for 5 years. Methods: Circulating concentrations of STC2, PAPP-A, total and intact IGFBP4 and IGF1 and -2 were measured at inclusion. End-points were all-cause mortality and a composite CVD event: death from CVD, myocardial infarction, stroke, revascularisation or amputation. Survival analysis was performed by Cox proportional hazards model. Results: During follow-up, 179 subjects presented with an event. After multivariable adjustment, higher levels of STC2, PAPP-A, as well as intact and total IGFBP4, were associated with all-cause mortality; STC2: hazard ratio (HR) = 1.84 (1.09–3.12) (95% CI); P = 0.023, PAPP-A: HR = 2.81 (1.98–3.98); P < 0.001, intact IGFBP4: HR = 1.43 (1.11–1.85); P = 0.006 and total IGFBP4: HR = 3.06 (1.91–4.91); P < 0.001. Higher PAPP-A levels were also associated with CVD events: HR = 1.74 (1.16–2.62); P = 0.008, whereas lower IGF1 levels were associated with all-cause mortality: HR = 0.51 (0.34–0.76); P = 0.001. Conclusions: This study supports that PAPP-A promotes CVD and increases mortality. However, STC2 is also associated with mortality. Given that STC2 inhibits the enzymatic effects of PAPP-A, we speculate that STC2 either serves to counteract harmful PAPP-A actions or possesses effects independently of the PAPP-A–IGF1 axis. Significance statement: PAPP-A has pro-atherosclerotic effects and exerts these most likely through IGF1. IGF1 is regulated by the STC2–PAPP-A–IGFBP4–IGF1 axis, where STC2, an irreversible inhibitor of PAPP-A, has been shown to reduce the development of atherosclerotic lesions in mice. We examined the association of this axis to mortality and CVD in T2D. We demonstrated an association between PAPP-A and CVD. All components of the STC2–PAPP-A– IGFBP4–IGF1 axis were associated with mortality and it is novel that STC2 was associated with mortality in T2D. Our study supports that inhibition of PAPP-A may be a new approach to reducing mortality and CVD. Whether modification of STC2 could serve as potential intervention warrants further investigation.

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.)

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo deletion of 4q34.1→qter associated with low pregnancy associated plasma protein-A (PAPP-A) and low placental growth factor (PlGF) in the first-trimester maternal serum screening, congenital heart defect (CHD) on fetal ultrasound and a false negative non-invasive prenatal testing (NIPT) result. Case Report: A 40-year-old, primigravid woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). First-trimester maternal serum screening at 12 weeks of gestation revealed low PAPP-A [0.349 multiples of the median (MoM)] and low PlGF (0.299 MoM) and showed a risk for fetal trisomy 21 and trisomy 13. However, NIPT detected no genomic imbalance and a normal result. Nevertheless, level II ultrasound revealed ventricular septal defect, single umbilical artery and a small brain midline cyst. Amniocentesis revealed a karyotype of 46,XX,del(4)(q34.1) and a 17.8-Mb deletion of 4q34.1q.35.2 on array comparative genomic hybridization (aCGH) analysis. The parental karyotypes were normal. The pregnancy was terminated at 23 weeks of gestation, and a malformed fetus was delivered with craniofacial dysmorphism. Postnatal cytogenetic analysis of the placenta confirmed the prenatal diagnosis. There was a 17.8-Mb deletion of 4q34.1q.35.2 encompassing the genes of HAND2, SORBS2 and DUX4. Polymorphic DNA marker analysis on the parental bloods and cord blood showed a paternal origin of the deletion. Conclusion: An abnormal first-trimester maternal serum screening result along with abnormal fetal ultrasound should alert the possibility of fetal aneuploidy, and amniocentesis is indicated even in the presence of a normal NIPT result.

Pregnancy-associated plasma protein-A (PAPP-A) is known as an important biomarker for fetal abnormality during first trimester and has a pivotal role in follicle development and corpus luteum formation. And also, it is being revealed that an expression of PAPP-A in various cells and tissues such as cancer and lesion area. PAPP-A is the major IGF binding protein-4 (IGFBP-4) protease. Cleavage of IGFBP-4 results in loss of binding affinity for IGF, causing increased IGF bioavailability for proliferation, survival, and migration. Additionally, PAPP-A can be used as a promising therapeutic target for healthy longevity. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. This review will focus on what is currently known about the zinc metalloproteinase, PAPP-A, and its role in cells and tissues. PAPP-A is expressed in proliferating cells such as fetus in uterus, granulosa cells in follicle, dermis in wound, cancer cells, and Sertoli cells in testis. They have common characteristics of proliferation faster than normal cells with stimulating IGFs action and inhibiting IGFBPs. The PAPP-A functions and expression studies in livestock have not yet been conducted much. Further studies are needed to use PAPP-A as a marker for healthy longevity in animal science.

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]

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]

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]

IntroductionPregnancy-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.MethodsThe 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.ResultsIn the twin cohort, PAPP-A increased with age (r=0.19; P

Senescence is a cellular response to various stressors characterized by irreversible cell cycle arrest, resistance to apoptosis and expression of a senescence-associated secretory phenotype (SASP). Interestingly, studies where senescent cells were deleted in mice produced beneficial effects similar to those where the zinc metalloproteinase, PAPP-A, was deleted in mice. In this study, we investigated the effect of senescence on PAPP-A secretion and activity in primary cultures of adult human pre-adipocytes. Cultured pre-adipocytes were isolated from subcutaneous (Sub) and omental (Om) fat. Senescence was induced with low dose etoposide. PAPP-A protein was measured by an ultrasensitive PAPP-A ELISA. PAPP-A proteolytic activity was measured by a specific substrate cleavage assay. Senescence significantly increased PAPP-A levels in both Sub and Om conditioned medium (CM) 8- to 15-fold over non-senescent CM. Proteolytic activity reflected PAPP-A protein with 12- to 18-fold greater activity in senescent CM versus non-senescent CM. Furthermore, PAPP-A was found at high levels on the surface of extracellular vesicles secreted by senescent pre-adipocytes and was proteolytically active. In conclusion, we identified enzymatically active PAPP-A as a component of human pre-adipocyte SASP. This recognition warrants further investigation of PAPP-A as a new biomarker for senescence and a potential therapeutic target to control of the spread of senescence in adipose tissue.

Aim: We aimed to investigate the placenta accreta index (PAI) score and first-trimester serum markers (pregnancy-associated plasma protein-a: PAPP-A, free beta human chorionic gonadotropin: free 0 HCG) in the prediction of Placenta Accreta Spectrum (PAS) in cases diagnosed with placenta previa (PP). Material and Methods: 30 PAS cases, 30 placenta previa cases without adhesion anomaly, and 60 healthy pregnants were included in our study. The PAI score was determined in the third trimester of the cases included in the study, then first-trimester serum markers and surgical outcomes (cesarean section, hysterectomy) were recorded. Results: In our study, when the cases in the PP and control groups were compared, PAPP-A(mlU/ml), PAPP-A MoM (Multiple of the median), and free 0 HCG MoM values were statistically significantly higher in the PP group (p<0.001). When PP and PAS cases were compared, we found that first-trimester serum markers were statistically significantly higher in the PAS group and the group undergoing peripartum hysterectomy (p<0.001). We found that the strongest parameter was the PAI score in predicting PAS, and first-trimester serum markers are as successful as PAI scoring. Conclusion: Considering that PAI scoring requires a certain experience in sonographic and technical terms and affects patient comfort in the transvaginal application, first-trimester serum markers can also be used because they have a similar value in predicting PAS. Using these data, we think referring patients to tertiary centers and multidisciplinary preoperative preparation that requires an experienced surgical team will help reduce perinatal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Pregnancy Associated Placental Protein-A (PAPP-A) is a zinc-binding metalloproteinase with a key role in the insulin-like growth factor (IGF) pathway. The IGF system plays an essential role in follicular development, including steroid hormone synthesis, growth, recruitment, and apoptosis of follicles of women undergoing intracytoplasmic sperm injection (ICSI). Objective: The objective of this study is to measure Pregnancy Associated Plasma Protein-A (PAPP-A) in serum of infertile women undergoing ICSI, and to investigate the association of PAPP-A with some reproductive hormones level. A total of 45 infertile women. Results: The results of this study was Serum PAPP-A level was not significant with hormones level (FSH, LH PRO and AMH) except E2 hormone was significant. Conclusion: Outcome show that no relation between studied reproductive hormones and serum PAPP-A except E2 levels that are high cause the egg to mature and release from the ovary. [ABSTRACT FROM AUTHOR]

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.)

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 (β-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

The exact mechanism by which aspirin prevents preeclampsia remains unclear. Its effects on serum placental biomarkers throughout pregnancy are also unknown. To investigate the effects of aspirin on serum pregnancy-associated plasma protein A and placental growth factor trajectories using repeated measures from women at increased risk of preterm preeclampsia. This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention trial using repeated measures of pregnancy-associated plasma protein A and placental growth factor. In the trial, 1620 women at increased risk of preterm preeclampsia were identified using the Fetal Medicine Foundation algorithm at 11 to 13+6 weeks of gestation, of whom 798 were randomly assigned to receive aspirin 150 mg and 822 to receive placebo daily from before 14 weeks to 36 weeks of gestation. Serum biomarkers were measured at baseline and follow-up visits at 19 to 24, 32 to 34, and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effect of aspirin on biomarker trajectories over time. Overall, there were 5507 pregnancy-associated plasma protein A and 5523 placental growth factor measurements. Raw pregnancy-associated plasma protein A values increased over time, and raw placental growth factor increased until 32 weeks of gestation followed by a decline. The multiple of the median mean values of the same biomarkers were consistently below 1.0 multiple of the median, reflecting the high-risk profile of the study population. Trajectories of mean pregnancy-associated plasma protein A and placental growth factor multiple of the median values did not differ significantly between the aspirin and placebo groups (aspirin treatment by gestational age interaction P values:.259 and.335, respectively). In women at increased risk of preterm preeclampsia, aspirin 150 mg daily had no significant effects on pregnancy-associated plasma protein A or placental growth factor trajectories when compared to placebo. [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.

Aim: to find out the predictive value of blood serum biochemical parameters PAPP-A (pregnancy-associated plasma protein A) and β-hCG (beta subunit of human chorionic gonadotropin) in the assessment of unfavorable pregnancy outcomes in women infected by human immunodeficiency virus (HIV) as well as viral hepatitis B (HBV) and C (HCV).Materials and Methods. A retrospective study of the medical records from 52 women was carried out, including 19 HIV-infected women, 9 women with monoinfection HBV or HCV, 11 pregnant women who were co-infected (HIV/HBV or HIV/HCV) and 13 uninfected women. PAPP-A and β-hCG levels, expressed as MoM (multiple of median), were evaluated in all women.Results. Our study revealed that only PAPP-A was prognostically significant for developing chronic placental insufficiency in women with HIV infection and co-infection of HIV together hepatitis B and C. None of the parameters examined were significant in women with HBV or HCV monoinfection. PAPP-A and β-hCG in pregnant women without infections were effective in predicting development of chronic placental insufficiency.Conclusion. PAPP-A can be used as a diagnostic parameter of developing chronic placental insufficiency in pregnant women with monoinfection HIV and co-infection with HIV/HBV or HIV/HCV.

Objective: We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome. Case report: A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766–90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20–30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16. Conclusion: Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

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]

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]

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]

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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]