Serum Pregnancy-associated Plasma protein-A Research Articles

The Relationship Between First-Trimester Aneuploidy Markers and Birth Weight

OBJECTIVE: We aimed to determine the relationship between the first-trimester aneuploidy screeningma and the predicted weight at birth: Small for gestational age and large for gestational age. STUDY DESIGN: 594 low-risk pregnant women with a singleton pregnancy, who underwent first-trimester aneuploidy screening by measuring nuchal translucency, maternal serum free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein-A were included in the study. Those weighing above the 3rd percentile and below the 10th percentile were defined as small for gestational age, and those over the 90th percentile were defined as large for gestational age. RESULTS: A total of 594 pregnant women were enrolled. The mean maternal age of the studied group was 28.8±5.5 years. Low maternal serum pregnancy-associated plasma protein-A levels and decreased nuchal translucency measurements were associated with the small for gestational age newborn (p<0.001 and p=0.001, respectively). There is a significant correlation with large for gestational age for newborns only with an increase in maternal serum pregnancy-associated plasma protein-A levels (p=0.001). beta-human chorionic gonadotropin levels were not associated with the birth weight (p=0.735). CONCLUSION: Maternal serum pregnancy-associated plasma protein-A levels, one of the markers in first-trimester aneuploidy screening, can be used in the prediction of small for gestational age and large for gestational age However, due to its low correlation, it is not a suitable screening test for clinical practice.

ASPRE trial: risk factors for development of preterm pre-eclampsia despite aspirin prophylaxis.

To examine the possible risk factors amongst maternal characteristics, medical and obstetric history, pre-eclampsia (PE)-specific biomarkers and estimated-risk group, according to The Fetal Medicine Foundation (FMF) algorithm, that are associated with the development of preterm PE with delivery at < 37 weeks' gestation despite aspirin prophylaxis. This was a secondary analysis of data from the ASPRE trial. The study population consisted of women with singleton pregnancy who were deemed to be at high risk for preterm PE, based on the FMF algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index, serum pregnancy-associated plasma protein-A and placental growth factor (PlGF) at 11-13 weeks' gestation. High-risk women were randomized to receive aspirin (150 mg/day) vs placebo from 11-14 until 36 weeks' gestation. The primary outcome was PE with delivery at < 37 weeks' gestation (preterm PE). Multivariate logistic regression analysis was performed to identify independent predictors of preterm PE after adjusting for the use of aspirin and other covariates. Among 1592 high-risk women, the incidence of preterm PE was 3.0% (n = 48). The interaction between aspirin usage and history of chronic hypertension was significant in the prediction of preterm PE (P = 0.042), which indicated that there was no treatment effect in high-risk women who had chronic hypertension compared with those who did not. Adjusting for aspirin use, the interaction between aspirin and chronic hypertension and other covariates, independent predictors for the development of preterm PE were PlGF multiples of the median (MoM) (adjusted odds ratio (aOR), 0.226 (95% CI, 0.070-0.723)) and estimated-risk group based on the FMF algorithm. Compared to women with an estimated risk of 1 in 51 to 1 in 100, those with an estimated risk of 1 in 2 to 1 in 10 had a 7-fold higher risk of developing preterm PE (aOR, 6.706 (95% CI, 2.381-18.883)), and those with an estimated risk of 1 in 11 to 1 in 50 had a 3-fold higher risk of preterm PE (aOR, 2.769 (95% CI, 1.105-6.939)). PlGF MoM was an independent predictor for preterm PE among women with an estimated risk of 1 in 2 to 1 in 10 (aOR, 0.055 (95% CI, 0.005-0.668)). Among women with an estimated risk of 1 in 11 to 1 in 100, the use of aspirin was an independent predictor of preterm PE (aOR, 0.276 (95% CI, 0.111-0.689)). The cut-off for PlGF with the best performance for the prediction of preterm PE was 0.712 MoM, with an aOR of 3.677 (95% CI, 1.526-8.862). In pregnancies at high risk of preterm PE identified by screening at 11-13 weeks' gestation using the FMF algorithm, a very high-risk result (estimated risk ≥ 1 in 50), compared to an estimated risk of 1 in 51 to 1 in 100, chronic hypertension, compared to no chronic hypertension, and low PlGF concentration (< 0.712 MoM), compared to PlGF ≥ 0.712 MoM, were associated with the development of preterm PE despite aspirin prophylaxis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age.

Accurate pregnancy dating is critical for maternal and child health and for counseling on safe and effective abortion methods. While last menstrual period and first trimester ultrasound are often used together to determine gestational age (GA), they have limited accuracy and availability, respectively. Prior studies have shown that pregnancy-associated plasma protein-A (PAPP-A) increases exponentially during pregnancy and has the potential to serve as a biochemical marker of GA. We aimed to analyze the relationship between sonographically determined GA and serum PAPP-A concentration measured by different immunoassays and to derive cutoff levels informative for the 70 days GA commonly recommended limit for medical abortion in outpatient settings. We compared technical characteristics of 4 commercially available PAPP-A immunoassays and tested 120 maternal serum samples (GA range: 34-231 days) along with contrived pool samples and traceable quality controls. These characteristics included area under the receiver operator characteristic (AUROC) plot, sensitivity and specificity based on cutoffs defined by the Youden Index, and likelihood ratios. All 4 immunoassays had sensitivities and specificities ≥80%, and AUROC values ranging from 0.948 to 0.968. Marked differences among absolute PAPP-A values were noted depending on immunoassay. PAPP-A cutoff values at 70 days GA for each individual immunoassay were established along with procedural recommendations that increase equivalence among immunoassays. Maternal serum PAPP-A levels correlated strongly with GA despite differences in immunoassay formats and absolute data output. Serum PAPP-A has biomarker potential for future development of a point-of-care test aimed at increasing access to medical abortion.

Combination of three-dimensional placental vascular indices and volume and uterine artery pulsatility index at 10-13 weeks of gestation could improve the prediction of adverse pregnancy outcomes.

To evaluate whether three-dimensional (3D) placental vascular indices and volumes during the first trimester of pregnancy can be used as predictors of subsequent adverse outcomes. This was a prospective cohort study including women with singleton pregnancies between 10 and 13 weeks. 3D placental volume and vascular indices and uterine artery pulsatility index (UtA-PI) were measured. Adverse outcomes were defined whether there was any of the following complications: small for gestational age pregnancy, preterm delivery, and preeclampsia. The serum pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) levels were also compared. We analyzed the screening performances of these parameters for prediction of any of adverse outcomes. Of 348 women screened, 300 women were completed follow-up. Overall, 57 (19.0%) of 300 women developed any of adverse pregnancy outcomes. Multiple logistic regression analysis demonstrated that gestational age-adjusted z-scores of log10 placental volume (odds ratio [OR], 0.572; 95% confidence interval [CI], 0.416-0.788), log10 placental vascularization flow index (VFI; OR, 0.676; 95% CI, 0.496-0.921), and log10 UtA-PI (OR, 1.910; 95% CI, 1.335-2.731) were significantly associated adverse pregnancy outcomes. The multivariate model combining placental VFI, placental volume, UtA-PI, and underweight or obese body mass index exhibited the highest screening performances (AUC=0.77) and PAPP-A and β-hCG did not add any significance to multivariate model. Placental volume and vascular indices at 10-13 weeks of gestation are significantly associated with adverse pregnancy outcomes. Combination of these placental indices and UtA-PI could improve the screening performance for adverse outcomes.

The Relationship between the Level of Pregnancy-Associated Plasma Protein A and Placenta Size and Thickness

Background: The low level of pregnancy-associated plasma protein A (PAPP-A) has a relationship with unfavorable outcomes in neonates. This study aimed to evaluate the association between the thickness and size of the placenta in singleton pregnant women. Materials and Methods: In this prospective cohort study, 102 women were investigated in 18-23 weeks and PAPP-A level at the gestational age in 11-14 weeks with a singleton pregnancy who referred to Al-Zahra Hospital, Rasht, Iran, between 2017 and 2018. Serum PAPP-A of pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤ 0.5 Multiple of the Median (MOM (were dedicated to an exposed group and others to a non-exposed group. Placental thickness and size were assessed during the second trimester by ultrasound examination and described as abnormal high thickness if the thickness was > 4 cm or more than 50% of the placental length and abnormally small size when the maximum length was < 10 cm. Then, placental thickness and size were compared between the two groups. Results: PAPP-A levels of > 0.5 and ≤ 0.5 were recorded in 60 and 34 patients, respectively. Women with low levels of PAPP-A in the first trimester had an increased incidence of abnormal placental thickness in 13 cases and small placental size in 7 cases, whereas this number was 12 and 7 cases, respectively, in the other group (P = 0.023). The sensitivity and specificity of PAPP-A < 0.55 were 72.3 and 56% for abnormal placental thickness, respectively; the sensitivity and specificity of PAPP-A < 0.55 were 69.3 and 57.1%, respectively, in the assessment of abnormal placenta size. Conclusion Based on the results, the size and thicknesses of the placenta were abnormal in women with a low level of PAPP-A (≤ 0.5).

REFERENCE CENTILE CHARTS OF PAPP-AAND FREE β-HCG IN INDIAN PREGNANT WOMEN.

The combined rst-trimester screening (CFTS) for fetal aneuploidy involves a combination of maternal age, fetal nuchal translucency (NT), maternal serum pregnancy-associated plasma protein-A(PAPP-A) and free β-human chorionic gonadotropin (β-hCG) from 11+0 to 13+6 weeks of gestation [1]. International prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the rst trimester are available and used throughout the world. Ethnicity has an effect on the biochemical parameters of rst trimester screening. As there is a lack of reference chart for the women of Indian ethnicity, we aimed to nd out the level of PAPP-Aand free β-hCG for fetal crown rump length (CRL) of 40-84 mm in the rst trimester of pregnancy and construct the centile charts for both the parameters. Asignicant but weak correlation between the individual models of PAPP-A and β-hCG and CRL (P&lt;0.001). In conclusion, the normal range of PAPP-A and free β-hCG depending on the gestation (CRL) was derived in this cohort study. This would act as a reference for our population and would be helpful in calculating the risk of an adverse maternal and fetal outcome.

Is it Possible to Predict Preeclampsia Early by Maternal Pregnancy Associated Plasma Protein-A and Uterine Artery Doppler? A Randomized-Controlled Trial

Background: Hypertensive disorders in pregnancy, along with IUGR and low birth weight, are among the major causes of maternal mortality and morbidity. It is one of the most common pregnancy complications. Its incidence ranges between 10-12% of all pregnancies. Early detection of preeclampsia (PE) is of utmost importance to start early intervention that prevents maternal and fetal comorbidities and decreases maternal and fetal mortality. Objectives: To predict the role of maternal serum pregnancy-associated plasma protein-A (PAPP-A) and uterine artery Doppler in females between 11-14 weeks of gestation for early detection of preeclampsia. Patients and methods: This randomized-controlled trial was done at Benha Teaching Hospital Department of Obstetrics & Gynecology over 200 pregnant women with gestational ages of 11-14 weeks. Blood pressure was recorded, uterine artery Doppler was done, and a blood sample for PAPP-A was drawn. Results: Uterine artery pulsatility index (PI) at 11-14 weeks of gestation is a good screening method for preeclampsia. The mean pulsatility index was more valid than PAPP-A. However, the combination of both in addition to patient history and blood pressure examination is more predictive. Conclusion: Our study concluded that at 11-14 weeks of gestation, uterine artery Doppler and serum level of maternal PAPPA-A were good screening methods for early prediction of preeclampsia.

Correlation analysis of serum placental growth factor, pregnancy-related plasma protein-A and disease severity in patients with hypertensive disorder in pregnancy.

To analyze the correlation of serum placental growth factor (PLGF), pregnancy-associated plasma protein-A (PAPP-A) and disease severity in patients with hypertensive disorders in pregnancy (HDP). Altogether 88 pregnant women with hypertensive disorder who underwent prenatal examination and delivery in our hospital from March 2017 to February 2019 were selected and included as the research group (n=88), and 62 healthy pregnant women who underwent prenatal examination during the same period were included as the normal control group (n=62). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of PAPP-A and PLGF in the serum of the two groups. The correlation of the expression levels of PAPP-A and PLGF with the severity of HDP was analyzed. The occurrence of adverse pregnancy outcomes in the two groups was compared, and the relationship of the expression levels of PAPP-A and PLGF with adverse pregnancy outcomes was compared. PAPP-A expression level in serum of pregnant women in the research group was significantly higher than that in the control group, while PLGF expression level was significantly lower than that in the control group (p<0.001). PAPP-A expression level was positively correlated with HDF severity (r=0.753, p<0.001), while PLGF expression level was negatively correlated with HDP severity (r=-0.929, p<0.001). The incidence of adverse pregnancy outcomes in the research group was significantly higher than that in the control group (p<0.05). The serum PAPP-A level of patients in the group with adverse pregnancy outcomes was significantly higher than that in the group without adverse pregnancy outcomes, while PLGF level was significantly lower than that in the group without adverse pregnancy outcomes (p<0.001). In conclusion, the expression levels of PAPP-A and PLGF in serum were closely related to the severity of HDP and could be used as indicators for disease monitoring.

Fetal fraction of cell free DNA in screening for hypertensive disorders at 11–13 weeks

Objective To investigate whether first-trimester maternal plasma fetal fraction is altered in women that subsequently develop preeclampsia (PE) or gestational hypertension (GH) and to examine its potential value in improving the performance of screening for PE and GH by maternal factors and maternal serum pregnancy associated plasma protein-A (PAPP-A), mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). Methods The study population of 10,131 pregnancies undergoing cell free fetal DNA testing at 11–13 weeks’ gestation included 91 (0.9%) cases with preterm-PE, 222 (2.2%) cases with term-PE, 360 (3.6%) with GH and 9,458 (93.4%) cases unaffected by hypertensive disorders. Maternal plasma fetal fraction levels were expressed as multiples of the median (MoM) after adjustment for maternal factors and crown-rump length. The performance of screening for preterm-PE, term PE and GH by maternal factors and MoM values of fetal fraction, PAPP-A, UtA-PI and MAP was evaluated by receiver operating characteristic (ROC) curves. Results The median fetal fraction MoM was significantly lower in the preterm-PE (0.825; IQR 0.689–1.115 MoM, p < .001), term-PE (0.946; IQR 0.728–1.211 MoM, p = .028) and GH (0.928; IQR 0.711–1.182 MoM, p < .001) groups than in the unaffected group (1.002; IQR 0.785–1.251 MoM). However, the performance of screening for PE or GH by maternal factors alone or by maternal factors and PAPP-A, UtA-PI and MAP was not significantly improved by the addition of fetal fraction. Conclusions First trimester maternal plasma fetal fraction is not useful in screening for hypertensive disorders of pregnancy.

First trimester serum PAPP-A is associated with placenta accreta: a retrospective study.

Our objective of this study was to investigate whether first trimester serum pregnancy-associated plasma protein-A (PAPP-A) differed amongst pregnancies with placenta previa-accreta and non-adherent placenta previa and healthy pregnancies by a retrospective cohort analysis. A total of 177 pregnant females were included in the study, as follows: 35 cases of placenta previa-accreta, 30 cases of non-adherent placenta previa, and 112 cases of BMI and age matched, healthy pregnant controls. PAPP-A multiples of the median (MoM) were acquired from laboratory data files in 1 January 2017-30 September 2019. The probable maternal serum biochemical predictor of placenta accreta was analyzed by using multiple logistic regression analysis. PAPP-A MoM of placenta previa-accreta group was significantly higher than those of the non-adherent placenta previa group and control group (p = 0.009 < 0.05, p < 0.001). Serum PAPP-A was found to be significantly positively associated with placenta accreta after adjusted gestational week at time of blood sampling, BMI, age, smoking, and previous cesarean section history (OR: 3.51; 95% CI: 1.77-6.94; p = 0.0003 < 0.05). In addition, smoking (OR: 9.17; 95% CI: 1.69-49.62; p = 0.010 < 0.05) and previous cesarean section history (OR: 2.75; 95% CI: 1.23-6.17; p = 0.014 < 0.05) were also significantly associated with placenta accreta. Increased first trimester serum PAPP-A was significantly positively associated with placenta accreta, suggesting that the potential role of PAPP-A in identifying pregnancies at high risk for placenta accreta. Smoking and previous cesarean section history may be the risk factors for accreta in placenta previa patients.

Suppression of PAPP-A mitigates atherosclerosis by mediating macrophage polarization via STAT3 signaling

Pregnancy-associated plasma protein-A (PAPP-A), a type of metalloproteinase in the insulin-like growth factor (IGF) system, has been implicated in atherosclerosis progression, but its function and mechanism in atherosclerosis is not fully understood. The study was performed to further explore the effects of PAPP-A on inflammation, macrophage polarization and atherosclerosis. In mouse macrophages stimulated by oxidized low-density lipoprotein (ox-LDL), PAPP-A expression was significantly increased. Its knockdown markedly mitigated inflammatory response and polarized macrophages to an M2-like phenotype in RAW264.7 cells upon ox-LDL treatment. Additionally, ox-LDL-induced activation of nuclear factor-κB (NF-κB) signaling pathway was dramatically restricted by PAPP-A knockdown in macrophages. However, JAK2/STAT3 activation was significantly up-regulated in RAW264.7 cells with PAPP-A inhibition after ox-LDL treatment. Importantly, we found that PAPP-A knockdown-induced polarization of M2-like phenotype in macrophages was mainly dependent on STAT3 activation. Clinical studies showed that serum PAPP-A levels were higher in patients with coronary artery disease (CAD) than that of healthy individuals. Apolipoprotein E-knockout (ApoE−/-) mice with high fat diet (HFD)-induced atherosclerosis exhibited higher expression of PAPP-A in aortas, which was mainly colocalized with F4/80. Subsequently, we found that PAPP-A deficiency greatly alleviated plaque formation, lesion burden and collagen accumulation in HFD-fed ApoE−/- mice. Consistent with in vitro macrophage phenotype, PAPP-A−/− reduced F4/80 expression, NF-κB activation and inflammatory response, while improved janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling and polarized macrophages to an M2-like phenotype in aortas of ApoE−/- mice after HFD feeding. In conclusion, these findings identified PAPP-A as a positive regulator of atherosclerosis by regulating macrophage polarization via STAT3 signal, and thus could be considered as a potential therapeutic target for atherosclerosis treatment.

Does the Addition of Serum PAPP-A and β-hCG Improve the Predictive Value of Uterine Artery Pulsatility Index for Preeclampsia at 11–14 Weeks of Gestation? A Prospective Observational Study

To study the role of uterine artery Doppler pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) levels, individually and in combination with each other, at 11-14 weeks of gestation for prediction of preeclampsia (PE).In a prospective observational study, a total of 100 low-risk gravid females were recruited at 11-14-weeks of gestation. UtA-PI, PAPP-A and fβ-hCG levels were estimated. These women were followed up until delivery for the development of PE and gestational hypertension (GH).The best individual marker for screening PE and GH was UtA-PI with ROC AUC (± standard error) = 0.934 ± 0.028, p < 0.0001. UtA-PI at a cutoff value of ≥ 2.8 (95th percentile) had 77.8% sensitivity, 98.9% specificity, 97.8% NPV and 87.5% PPV in detecting PE. PAPP-A (MoM) at a cutoff value of ≤ 0.27 (5th percentile) demonstrated 44.4% sensitivity, 95.6% specificity, 94.5% NPV and 50% PPV. fβ-hCG (MoM) at a cutoff value of ≤ 0.5 (5th percentile) had a specificity of 94.5%. Among the combined markers, UtA-PI along with PAPP-A estimation served best with a sensitivity and specificity of 44% and 100%, respectively. Addition of fβ-hCG to either UtA-PI or PAPP-A levels was not found sensitive for detecting PE but yielded 100% specificity and 96% NPV.UtA-PI as a stand-alone test was found most useful for the prediction of PE. Addition of either or both of PAPP-A and fβ-hCG to UtA-PI did not improve the sensitivity of combined test with only a slight improvement in specificity and NPV. Their routine addition to UtA-PI studies is not recommended for prediction of PE at 11-14 weeks of gestation in low- and lower-middle-income countries (LMIC).

Maternal Pregnancy Associated Plasma Protein-A Levels in Late First Trimester as a Predictor of Miscarriage- A Cross-sectional Study

Indroduction: Miscarriage is the most common complication of pregnancy. Defective implantation is one of the common causes of miscarriage. Pregnancy Associated Plasma Protein-A (PAPP-A) is secreted from syncytiotrophoblast and it enables trophoblast invasion. Few studies have shown association of PAPP-A with miscarriage. However, there is limited data available to establish the role of PAPP-A as a predictive marker of miscarriage, especially in Indian population. Aim: To determine the potential of maternal PAPP-A level estimation in asymptomatic women in late first trimester (10-13 weeks) with viable foetus in predicting subsequent miscarriage. Materials and Methods: This was an observational, cross-sectional study conducted from November 2016 to April 2018 at University College of Medical Science and Guru Teg Bahadur Hospital, Delhi, India. Asymptomatic pregnant women (N=500) at 10-13 weeks of gestation were recruited from an antenatal clinic after confirmation of foetal viability. A 2 mL of blood sample was collected and serum PAPP-A level was measured. Independent t-test and Chi-square test was used to compare continuous data and Mann-Whitney U test was used to compare PAPP-A Multiple of Median (MOM). Logistic regression was used to estimate risk of miscarriage. Results: Out of 500 participants, 9 were lost to follow-up. From remaining N=491, 32 (6.5%) women had a miscarriage. PAPP-A levels were significantly decreased in miscarriage group compared to ongoing pregnancy group with median MOM 0.116 (0.080-0.17) and 1.25 (0.665-3.249) respectively (p-value &lt;0.001). PAPP-A MOM value of ≤10th percentile sensitivity and specificity of detection of miscarriage was 81.25% and 94.98% and at ≤5th percentile sensitivity and specificity was 40.62% and 97.82%, respectively. Lower the percentile cut-off of serum PAPP-A value, higher was the specificity and positive predictive value for prediction of miscarriage. By applying logistic regression we found that if PAPP-A MOM decreases by 1 unit the chances of miscarriage increased by 1.2 times. By this model 63.2% of cases could be explained (Nagelkerke R Square=0.632). For prediction of pregnancies likely to miscarry, the area under Receiver Operator Characteristic (ROC) curve (95% CI) was 0.969 (0.955-0.983). Conclusion: Low serum PAPP-A levels from asymptomatic women in late 1st trimester is a good predictive marker of miscarriage.

IGFBP-4: A promising biomarker for lung cancer.

Background: Insulin-like growth factor binding protein-4 (IGFBP-4), a member of the insulin-like growth factor (IGF) family, transports, and regulates the activity of IGFs. The pregnancy-associated plasma protein-A (PAPP-A) has proteolytic activity towards IGFBP-4, and both proteins have been associated with a variety of cancers, including lung cancer. Thus, we aimed to evaluate the use of IGFBP-4 and PAPP-A as potential biomarkers for lung cancer. Methods: Eighty-three volunteers, including 60 patients with lung cancer and 23 healthy individuals, were included in this study. The patients with lung cancer were selected based on their treatment status, histological subgroup, and stage of the disease. Enzyme-linked immunosorbent assays were used to assess the serum levels of IGFBP-4 and PAPPA, whereas the IGF-1 levels were measured using a chemiluminescent immunometric assay. Results: The serum IGFBP-4 levels in all patient groups, regardless of the treatment status and histological differences, were significantly higher than those in the control group (p<0.005). However, the serum PAPP-A levels in the untreated patient group were found to be higher than those in the control group, but this difference was not statistically significant (p=0.086). Conclusions: The serum PAPP-A and IGFBP-4 levels are elevated in lung cancer. However, IGFBP-4 may have better potential than PAPP-A as a lung cancer biomarker.

Maternal serum pregnancy-associated plasma protein-A concentration at 11–14 weeks of gestation of women with common congenital anatomic uterine abnormalities

Maternal serum pregnancy-associated plasma protein-A concentration at 11–14 weeks of gestation of women with common congenital anatomic uterine abnormalities

Diagnostic Test of Serum Pregnancy-Associated Plasma Protein-A Level as Biomarker for Early Diagnosis of Acute Myocardial Infarction

Acute coronary syndrome is the primary cause of death from heart disease worldwide. This syndrome is caused by ruptured/eroded coronary atherosclerotic plaque, resulting in partial/total occlusion of thrombosis. It is necessary to find novel cardiac biomarkers for the identification of plaque progression before ischemic and myocardial necrosis events. Pregnancy Associated Plasma Protein-A (PAPP-A) is an atherosclerotic mediator proven to be a biomarker for plaque instability. This study aimed to determine the performance of serum PAPP-A as a biomarker for the early diagnosis of AMI. This research was an analytical observational study with a cross-sectional approach. Serum PAPP-A was measured using enzyme-linked immunosorbent assay in 82 new patients. They had ACS and were admitted to the emergency installation of Dr. Moewardi Hospital in Surakarta in August-September 2019. The subjects were grouped into the AMI group (NSTEMI and STEMI) consisting of 49(59.8%) subjects and non-AMI (UAP) group composed of 33(40.2%) subjects based on ACS diagnostic criteria of PERKI 2018. Receiver Operator Characteristic (ROC) curve analysis showed that PAPP-A was a good discriminator between AMI and non-AMI patients. The area under the curve was 0.968, 95% CI (0.932–1.004), with a sensitivity of 91.8% and specificity of 90.9% (p&lt; 0.05). The cut-off value from the ROC curve was 2,526 ng/mL. Serum PAPP-A level has excellent performance as a biomarker for early diagnosis of AMI. It can also function as a screening instrument for the identification of UAP cases developing into AMI.

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study

BackgroundThe purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use.MethodsA routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9–11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11–13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed.ResultsFree β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups.ConclusionsThe present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

Pregnancy-Associated Plasma Protein-A2 Is Associated With Mortality in Patients With Lung Cancer

Pregnancy-associated plasma protein-A (PAPP-A) and its homolog PAPP-A2 are enzymes that modulate the availability and mitogenic activity of insulin-like growth factor-I (IGF-I). PAPP-A has been implicated in numerous cancers but reports on PAPP-A2 in malignancy are non-existent. In a prospective observational study of 689 patients under suspicion of lung cancer, we examined levels of PAPP-A and PAPP-A2 and their relationship with mortality. Serum PAPP-A and PAPP-A2 concentrations were determined in pre-diagnostic blood samples using ELISA, and immunohistochemical staining of PAPP-A and PAPP-A2 was performed in malignant tissue from five operable patients. A total of 144 patients were diagnosed with lung cancer, whereas the diagnosis was rejected in 545 subjects, who served as a control group. PAPP-A2 concentrations were higher in patients with lung cancer [median (IQR): 0.33 (0.21–0.56) ng/mL] than in controls [0.27 (0.17–0.39) ng/mL], p < 0.001, whereas PAPP-A levels did not differ. Presence of PAPP-A and PAPP-A2 were confirmed in tumor specimens, and staining occurred in a heterogeneous pattern. Patients were observed for a median (range) of 7 (6; 8) years, during which 114 patients (79.2%) died. Patient mortality differed according to PAPP-A2 tertile (p < 0.001). PAPP-A2 was associated with mortality with an unadjusted hazard ratio (95% CI) per doubling in protein concentration of 1.30 (1.12; 1.53), p = 0.001. In a multivariable model adjusted for age, sex, and BMI, PAPP-A2 remained predictive of the endpoint with a hazard ratio per doubling in protein concentration of 1.25 (1.05; 1.48), p = 0.013. Collectively, PAPP-A2, but not PAPP-A, is elevated in patients with lung cancer and associated with mortality. This novel role of PAPP-A2 in cancer warrants further functional studies as well as validation in external cohorts.

Evaluation of serum pregnancy associated plasma protein-A levels in patients with rheumatoid arthritis

Evaluation of serum pregnancy associated plasma protein-A levels in patients with rheumatoid arthritis

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor β1(TGF-β1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-β1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-β1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.