Comparison of Pregnancy Associated Plasma Protein A (PAPP-A) Levels in IVF-Induced Pregnancies and Physiological Pregnancies: A Case-Control Study

Pregnancy-associated plasma protein A (PAPP-A), also known as insulin-like growth factor binding protein 4 protease, is postulated to be a new inflammatory marker in various clinical situations such as cardiovascular events, dialysis, renal transplantation, and asthma. PAPP-A also is produced in high concentrations by trophoblasts during pregnancy. We evaluated PAPP-A levels in allergic rhinitis patients and compared these with levels in healthy subjects. Thirty-one newly diagnosed allergic rhinitis patients and 29 healthy controls were included in the study. Serum PAPP-A, IgE, urea, creatinine, aspartate aminotransferase, creatine kinase (CK), CK-MB isoenzyme, total cholesterol, and triglyceride levels were determined. The serum PAPP-A level was significantly higher (p = 0.013) in the allergic rhinitis group (6.1 +/- 2.9 mU/L) than in the control group (4.5 +/- 1.7 mU/L). The PAPP-A level in patients with allergic rhinitis and asthma (6.1 +/- 2.3 mU/L) was not significantly different (p = 0.959) from that in patients with allergic rhinitis alone (6.1 +/- 3.3 mU/L). The serum PAPP-A level in allergic rhinitis patients who had turbinate hypertrophy (6.9 +/- 2.2 mU/L) had a tendency to be higher than that in patients who had no turbinate hypertrophy (5.5 +/- 3.2 mU/L); however, this difference was not statistically significant (p = 0.151). Increased PAPP-A activity may be involved in the inflammation and tissue remodelling that occurs in allergic rhinitis.

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. Impact statement 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.

IntroductionPsoriasis is an immune-mediated chronic inflammatory dermatosis. Several studies have shown that patients with psoriasis have a much greater risk of cardiovascular diseases than the normal population. The chronic inflammation observed in psoriasis is thought to have a role in the development of atherosclerosis and vascular endothelial injury.AimTo examine serum pregnancy-associated plasma protein-A (PAPP-A) levels, which has been regarded as a marker of early stage atherosclerosis in patients with psoriasis that do not have concurrent conventional cardiovascular risk markers.Material and methodsForty-one patients diagnosed with a chronic plaque type of psoriasis and 42 equally matched healthy volunteers were included in this study. The PAPP-A levels were compared between patient and control groups and the association between PAPP-A levels and disease duration and severity were evaluated in the patient group.ResultsStatistically, serum PAPP-A levels were significantly higher in the psoriasis group than in the control group (p = 0.015). Serum PAPP-A levels were found to be positively correlated with severity (p = 0.036, r = 0.329) and duration (p = 0.014, r = 0.269) of the disease.ConclusionsAs a marker of early stage atherosclerosis, PAPP-A levels were elevated in the psoriasis group and were correlated with disease duration and severity. This elevation reveals the presence of atherosclerosis in patients with psoriasis. Further studies are needed to confirm the use of PAPP-A as an available and inexpensive screening test and cardiovascular risk assessment for all centers.

Aim. To analyse the levels of serum beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women without fetal chromosomal abnormalities and with fetal trisomy 21 (Down syndrome) or 18 (Edwards syndrome).Materials and Methods. We performed a retrospective analysis of serum biochemical parameters of 1214 women who had previously undergone karyotyping as a part of prenatal or postnatal screening. Patients were stratified into those with a normal fetal karyotype, those carrying a fetus with trisomy 21, and those carrying a fetus with trisomy 18. Levels of serum β-hCG and PAPP-A were estimated using the AutoDELFIA automatic immunoassay system.Results. In most of the women carrying a fetus with trisomy 21, serum β-hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b -hCG has been increased as compared to the reference range. In contrast, women carrying a fetus with trisomy 18 generally had reduced serum β-hCG. In both cases, the level of serum PAPP-A has been decreased in comparison with a reference range. The proportion of women with a 2-fold reduced serum PAPP-A was 52.4% and 88.6% if carrying fetuses with trisomy 21 and trisomy 18, respectively.Conclusion. Serum b-hCG and PAPP-A are sensitive markers of fetal trisomy 21 and trisomy 18 in pregnant women.

BackgroundThis study aimed to compare serum levels of vascular endothelial growth factor (VEGF) and the VEGF receptors, VEGFR-1 and VEGFR-2, free placental growth factor (fPGF), endostatin, and serum pregnancy-associated plasma protein-A (PAPP-A) levels in women with mild and severe preeclampsia and healthy pregnant women.Material/MethodsA included patients diagnosed with mild preeclampsia (n=32), severe preeclampsia (n=32), and healthy pregnant women (n=24). Serum levels of VEGF-A, VEGFR-1, VEGFR-2, fPGF, endostatin, and PAPP-A levels were measured by enzyme-linked immunosorbent assay (ELISA).ResultsIn women with mild and severe preeclampsia, the gestation age at birth and birth weight were found to be significantly lower than the control group (p<0.001). Serum levels of endostatin, VEGFR-1, and VEGF-A levels were significantly increased in pregnant women with preeclampsia compared with healthy pregnant women (p<0.001). Serum levels of PAPP-A, VEGFR-2, and fPGF were significantly higher in healthy pregnant women when compared with women with preeclampsia (p=0.024, p<0.001, and p<0.001, respectively), but there were no significant differences between women with mild and severe preeclampsia.ConclusionsReduced serum levels of the angiogenic factors PAPP-A, VEGFR-2, and fPGF distinguished between women with preeclampsia and normotensive pregnant women but did not significantly distinguish between mild and severe preeclampsia.

First-trimester screening for trisomy 21 in pregnancies conceived by in vitro fertilization

Aim: to evaluate the ability of serum biochemical markers in pregnant woman - PAPP-A (pregnancy-associated plasma protein-A) and β-hCG (the в-subunit of human chorionic gonadotropin) studied in the first trimester (11 +0 -13 +6 ) during combined prenatal screening to predict adverse perinatal outcomes of multiple pregnancy that occurred spontaneously and as a result of in vitro fertilization (IVF). Materials and methods . The main group consisted from 65 women with pregnancy occurred as a result of IVF; comparison group included 56 women with spontaneous pregnancy. All pregnancies were multiple and their outcomes were known. Serum PAPP-A and β-hCG levels were measured in the first trimester. The results were expressed in absolute values and in MoM (multiples of median). Subgroups were compared with mono- and dichorionic pregnancies, complicated and uncomplicated pregnancies, distributed according to MoM index: within the reference values (0.5-2.0), below or above the reference values. Results . PAPP-A MoM values in the spontaneous pregnancy group were 1.12 [0.8; 1.57], in the IVF group - 1.35 [1.11; 1.72] (p = 0.01). In subgroup of low PAPP-A MoM antenatal fetal death occurred in 50 %, in subgroup of normal PAPP-A MoM - in 14.58 %, in subgroup of high PAPP-A MoM - in 5.88 % (p = 0.011). In addition, a positive correlation was found between serum PAPP-A level and time of fetal death (r s = 0.564; p = 0.036). Low PAPP-A MoM values were associated with 50 % fetal mortality, 75 % of them were attributable to pregnancy as a result of IVF. Conclusion . Identification of adverse outcomes in multiple pregnancies is still a difficult task, but evaluation of serum biochemical markers during the first trimester screening can help in early diagnosis of necessity and extent of timely prophylaxis.

ObjectiveTo evaluate the association between first-trimester serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) and the development of intrauterine growth restriction (IUGR), in order to assess their utility in early screening for improved perinatal outcomes.MethodsA retrospective case–cohort study was conducted at Marqués de Valdecilla University Hospital in 2021, including 119 pregnancies with IUGR and a randomly selected subcohort of 383 pregnancies from the same population. Serum levels of PAPP-A and β-hCG were analyzed both as continuous variables and as categorical variables based on population-specific percentiles (< 10th and < 5th). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for relevant maternal and obstetric covariates.ResultsLower PAPP-A levels were significantly associated with an increased risk of IUGR, both as a continuous variable (OR = 0.50; 95% CI: 0.34–0.76, p = 0.001) and when categorized below the 10th percentile (OR = 4.01; 95% CI: 1.78–9.01, p < 0.001) and 5th percentile (OR = 4.45; 95% CI: 1.57–12.63, p = 0.005). β-hCG showed no association when analyzed continuously (p = 0.164), but values below the 10th percentile were significantly associated with IUGR (OR = 4.45; 95% CI: 1.97–10.04, p < 0.001). No reliable estimate could be obtained at the 5th percentile due to the small number of cases.ConclusionIncorporating PAPP-A and β-hCG into first-trimester screening protocols could enable earlier identification of pregnancies at risk of IUGR, facilitating timely interventions and potentially improving maternal and neonatal outcomes. These findings support the clinical utility of these biomarkers in routine obstetric care.

ObjectiveRecently, strong evidences were obtained on the association between low pregnancy-associated plasma protein-A (PAPP-A) levels in the first trimester and poor outcomes of pregnancy.MethodsThis cross-sectional study was conducted on all pregnant women who were referred to the Obstetrics and Gynecology Clinic at Imam Hossein Hospital in Tehran, Iran in 2014. Women were asked to attend clinical examinations and screening at 11–14 weeks of gestation.ResultsBased on the definition, 14.5% of neonates found to be small for gestational age (SGA). There was a strong association between PAPP-A levels and birth weight. The mean PAPP-A level in the mothers of neonates who were SGA was significantly lower than those without this poor outcome. Based on the receiver operating characteristic curve analysis, serum PAPP-A level was a main determinant in the prediction of SGA neonates.ConclusionThe serum PAPP-A level at 11–13 weeks of gestation can effectively predict the increased risk for fetal growth retardation. In patients in this study, the best cutoff value for PAPP-A was 0.75 MOM, which signifies that lower levels of this marker can predict fetal growth restriction with high sensitivity and specificity.

Background: Remodeling is a crucial feature of severe asthma and may be associated with activation of the allergic cascade by immunoglobulin E (IgE). Omalizumab, an anti-IgE monoclonal antibody, effectively targets the severe allergic asthma phenotype. Pregnancy-associated plasma protein-A (PAPP-A) is an insulin-like growth factor binding protein-4 (IGFBP-4) protease, increasing local insulin-like growth factor (IGF)-1 concentrations, which in turn initiating a cascade involved in the regulation of cell growth, differentiation, and proliferation in various tissues. In the present study, we evaluated the effects of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe allergic asthma. Methods: We studied 36 asthmatic subjects and 36 healthy controls. An ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit was used to measure serum PAPP-A levels, and routine commercial ELISA kits were employed to assess serum levels of IGF-1, IGFBP-4 in control subjects and asthmatic subjects before therapy (baseline) and after six months of omalizumab therapy in patients with severe asthma. Results: Compared to control subjects, serum PAPP-A and IGFB-4 levels were significantly higher in asthmatic subjects (both p values < 0.001). However, the serum IGF-I levels of asthmatic subjects were similar to those of control subjects (p > 0.05). In asthma subjects, 6-month omalizumab treatment significantly decreased the serum PAPP-A (p < 0.001), IGF-I (p = 0.031), and IGFB4 (p = 0.025) levels. Conclusion: PAPP-A level may be a useful biomarker for predicting airway remodeling in patients with severe asthma receiving omalizumab, and may also reflect the response to treatment.

First trimester serum concentrations of placental proteins in singleton and multiple IVF pregnancies: implications for Down syndrome screening

High Serum Level of Pregnancy Associated Plasma Protein A (PAPP-A) is a Risk Factor of Patients With Heart Failure

Background: The aim of the study was to determine pregnancy-associated plasma protein-A (PAPP-A), which was recently described as a new marker of cardiovascular events, in patients with chronic renal insufficiency/failure and to find out its relationship to renal function and to prominent markers of oxidative stress (advanced oxidation protein products – AOPP) and inflammation (C-reactive protein – CRP). Methods: The studied group consisted of 36 chronic hemodialysis patients (HD), 10 patients treated with continuous ambulatory peritoneal dialysis (CAPD) and 38 patients with chronic renal insufficiency (CHRI) not yet dialyzed. PAPP-A was measured by Time Resolved Amplified Cryptate Emission technology. Determination of AOPP is based on a spectrophotometric method. Results: PAPP-A levels are statistically significantly elevated in the both groups of dialyzed patients in comparison with healthy subjects (27.0 ± 16.5 mIU/l in HD and 14.07 ± 6.73 mIU/l in CAPD vs. 8.22 ± 2.7 mIU/l in the control group, p < 0.0001 and p < 0.001, respectively, p < 0.05 HD vs. CAPD). The mean serum PAPP-A levels in the CHRI patients not yet dialyzed were not significantly higher in comparison with the control group (9.72 ±4.44 vs. 8.22 ± 2.7 mIU/l, n.s.). In the CHRI not dialyzed patients, we found a significant positive correlation between serum creatinine and PAPP-A levels (r = 0.68, p < 0.05). In comparison with controls, AOPP and CRP levels were significantly higher in HD patients [AOPP 155.0 ± 37.9 µmol/l, p < 0.0001 vs. controls, CRP 10.0 (4.6– 26.9) mg/l (median, interquartile range), p < 0.0001 vs. controls], CAPD patients [AOPP 118.5 ± 25.8 µmol/l, p < 0.0001 vs. controls, CRP 7.7 (2.0–18.8) mg/l, p < 0.01 vs. controls] and AOPP levels in chronic renal failure patients not yet dialyzed (98.5 ± 43.24 µmol/l, p < 0.01 vs. controls). The correlations between PAPP-A and AOPP (r = 0.49, p < 0.05) and PAPP-A and CRP (r = 0.48, p < 0.05) serum concentration were statistically significant in HD patients. In CAPD patients, neither a correlation between PAPP-A and AOPP nor a correlation between PAPP-A and CRP were found. Conclusion: We can conclude that serum PAPP-A levels sensitively reflect the changes in renal function, depend on dialysis modality, and may represent a novel marker associated with inflammation and oxidative stress in chronic renal failure patients.

Objective To study the correlation between serum pregnancy associated plasma protein A (PAPPA) level of pregnant women and pregnancy complications. Methods From Sep. 2010 to Dec. 2016, 4 920 Down syndrome screening cases in our hospital were selected as observation group, and during the same period 2 350 normal pregnant women were selected as control group. All the pregnant women were followed up and their data were collected and analyzed, and the serum PAPPA levels in the two groups were compared. Results 3 400 cases in the observation group were successfully followed up, including 2 145 cases with normal pregnancy and prognosis (63.09%), 71 cases with spontaneous abortion or termination of pregnancy (2.09%), 65 cases with threatened abortion (1.91%), 48 cases with pregnancy induced hypertension syndrome (1.41%), 99 cases with gestational diabetes (2.91%), and 156 cases with gestational impaired glucose tolerance (4.59%). 1 700 cases in the control group were successfully followed up. The statistical analysis showed that the serum PAPPA level in the observation group was significantly lower than that in the control group at different gestational weeks (P<0.05). The lower the serum PAPPA level was, the higher the incidences of spontaneous abortion or termination of pregnancy, threatened abortion, pregnancy induced hypertension syndrome, gestational diabetes, and gestational impaired glucose tolerance were. Conclusion The low serum PAPPA level of pregnant women can promote the occurrence of pregnancy complications, such as spontaneous abortion, threatened abortion, pregnancy induced hypertension syndrome, and gestational diabetes. Key words: Pregnant women; Serum PAPPA; Pregnancy complications

Positive correlation between pregnancy-associated plasma protein-A level and OX40 ligand expression in patients with acute coronary syndromes