Serum Pregnancy-associated Plasma protein-A Concentrations Research Articles

The significance of fetal maxillary length in the first trimester screening for trisomy 21

The present study aims to specify the significance of fetal maxillary length by establishing a nomogram for a Turkish population and by investigating its relationship with the ultrasonographic and biochemical parameters which are commonly used to screen trisomy 21 in the first trimester of pregnancy. The present observational study investigates 1,308 Turkish women who had 11- to 14-week-old singleton healthy pregnancies. Fetal crown-rump length (CRL), nuchal translucency (NT), nasal bone length (NBL) and maxillary length are measured by ultrasonography and maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (HCG) are determined. A positive and significant correlation was detected between the fetal maxillary length and gestational age (r = 0.309, P < 0.001) as was the case with fetal CRL (r = 0.357, P < 0.001) and NBL (r = 0.487, P < 0.001). Although there was a significant and positive correlation between fetal maxillary length and maternal serum PAPP-A levels (r = 0.201, P < 0.001), a significant and negative correlation was found between fetal maxillary length and the maternal serum concentrations of free beta-HCG (r = -0.238, P < 0.001). Fetal maxillary length increased in accordance with the advancing gestational age and increasing CRL. Maternal serum PAPP-A concentrations and fetal CRL and NBL were addressed as independent predictors of fetal maxillary length. The length of fetal maxillary bone is a promising biometrical parameter which can be reliably and efficiently used to screen trisomy 21 in first trimester. Fetal maxillary length is also found to correlate with gestational age, CRL, NBL and PAPP-A significantly. It would be rational to use a combination of nasal and maxillary bone length measurements in case serum concentrations of PAPP-A or beta-HCG cannot be assessed.

Intravenous Administration of Low Molecular Weight and Unfractionated Heparin Elicits a Rapid Increase in Serum Pregnancy-Associated Plasma Protein A

Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful diagnostic and prognostic marker in acute coronary syndromes. Because low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used in these cases, we analyzed the effects of intravenous administration of these heparins on serum PAPP-A concentrations. Serum concentrations of total and free PAPP-A were analyzed in 14 patients on chronic hemodialysis and in 10 coronary angiography patients. Ten of the dialysis patients received standard LMWH anticoagulation at the start of dialysis, and 4 were treated with a heparin-free method. Two of the patients on heparin-free hemodialysis received a reduced LMWH bolus 2 h after the start of dialysis. All angiography patients received UFH at the start of the procedure, and 1 patient received 2 extra boluses of UFH. Serum PAPP-A concentrations were analyzed before and during the dialysis session and during the coronary angiography examination. A rapid increase in total PAPP-A (median, 25-fold) was seen in all patients within 5 min of administration for both LMWH and UFH boluses. This response was due to an increase in free PAPP-A in the serum. PAPP-A did not increase significantly in the patients who underwent heparin-free hemodialysis. Repeated heparin boluses induced a new PAPP-A release. In vitro addition of heparins to samples of whole blood did not increase PAPP-A concentrations. Intravenous administration of heparin induces an intense and rapid increase in free PAPP-A in the serum. We recommend that this effect be considered when PAPP-A is assessed as a biomarker in acute coronary syndromes.

The Impact of First-Trimester Serum Free β-Human Chorionic Gonadotropin and Pregnancy-Associated Plasma Protein A on the Diagnosis of Fetal Growth Restriction and Small for Gestational Age Infant

Objective: To evaluate the risk of fetal growth restriction (FGR) associated with first-trimester maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG). Methods: A longitudinal study of 2,178 women who underwent first-trimester evaluation of serum PAPP-A and free β-hCG. FGR was defined as a decrement of the fetal abdominal circumference to below the 10th percentile of our standard growth curve in the presence of Doppler signs of impaired placental perfusion. Logistic regression was used to compute multivariable odds ratios and the estimated prevalences of outcomes associated with first-trimester serum marker concentrations. Results: The prevalences of small for gestational age (SGA, <10th percentile birth-weight) neonates and FGR were significantly higher among women with serum PAPP-A concentrations below the 10th percentile than in controls: 40/206 compared to 183/1,928, for SGA, adjusted odds ratio = 2.1, 95% confidence intervals (CI) 1.4–3.03; 24/75 compared to 182/1,900, for FGR, adjusted odds ratio = 3.9, 95% CI 2.3–6.5. The adjusted prevalences of FGR and SGA among women with simultaneous low first-trimester values of PAPP-A and free β-hCG were 0.21 (95% CI 0.13–0.33) and 0.26 (95% CI 0.17–0.36), respectively. Conclusion: Low first-trimester maternal serum PAPP-A concentrations are significantly associated with reduced fetal size and increased risk of FGR with Doppler signs of impaired placental perfusion.

Pregnancy-associated plasma protein-A and asthma

Pregnancy-associated plasma protein-A (PAPP-A) is potentially a proatherosclerotic metalloproteinase and a new inflammatory marker. Investigators sought to evaluate the significance of PAPP-A in patients with asthma. Blood samples were collected from 35 patients and 20 control subjects. Serum PAPP-A was determined by enzyme-linked immunosorbent assay. PAPP-A levels of patients with asthma (8.1+/-5.0 mU/L) were higher than those of the control group (4.9+/-2.1 mU/L) (P<.01). A significant correlation was noted between serum PAPP-A concentration and asthma severity (r=.581; P<.01). Investigators concluded that PAPP-A may contribute to airway smooth muscle hyperplasia as an insulin-like growth factor-dependent insulin-like growth factor-binding protein-4 protease in patients with asthma.

Comment on Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes

Qin et al. (1) recently discussed the limitations of pregnancy-associated plasma protein-A (PAPP-A) immunoassays developed for use during pregnancy to study acute coronary syndromes (ACS). That report and the authors’ related article in Clinical Chemistry (2) have important implications, because PAPP-A has been suggested to be a prognostic marker of cardiac risk (3). We have reported on the direct relationship between serum PAPP-A concentrations and both the extent and complex morphology of angiographic coronary artery stenoses in patients with chronic stable angina pectoris (4)(5). These studies were performed with the same assay that was used in the first clinical report on PAPP-A and ACS by Bayes-Genis et al., who described a relationship between PAPP-A and unstable atherosclerotic plaques (3). This assay was based on a polyclonal capture antibody and a combination of monoclonal detection antibodies. It was calibrated with WHO reference standard 78/610, which was derived from serum collected from pregnant women. The findings of Qin et al. (1)(2), raise questions concerning …

Increased Pregnancy-Associated Plasma Protein-A as a Marker for Peripheral Atherosclerosis: Results from the Linz Peripheral Arterial Disease Study

The aim of the present investigation was to test the hypothesis that pregnancy-associated plasma protein-A (PAPP-A), a zinc-binding metalloproteinase implicated in acute coronary syndrome, is associated with atherosclerotic peripheral arterial disease (PAD). The study comprised 433 patients with symptomatic atherosclerotic PAD (i.e., chronic limb ischemia) and 433 controls matched to the patients with PAD in a 1:1 design by sex, age (+/-2 years), and diabetes mellitus status. Serum PAPP-A concentrations were measured with an enzymatically amplified 2-step sandwich-type immunoassay. The entire study sample included 612 male and 254 female patients with a median age of 68 years. The median PAPP-A value was higher in the patients with PAD than in the referents (0.81 vs 0.64 mU/L; P <0.001). After we adjusted for several possible confounding variables with multivariable logistic regression, odds ratios for PAD were 1.59 (95% confidence interval, 1.00-2.52; P = 0.049), 2.28 (1.45-3.61; P <0.001), and 2.86 (1.78-4.59; P <0.001) in the 2nd, 3rd, and 4th quartiles of serum PAPP-A concentrations compared with the first quartile. In the present study, PAPP-A added to the predictive value of other markers commonly in use. PAPP-A was associated with atherosclerotic PAD in the elderly sample studied. Because atherosclerotic PAD is considered an indicator of systemic atherosclerotic disease in elderly patients, the present results indicate that circulating PAPP-A may be a marker for systemic atherosclerotic disease.

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome

Objectives: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. Methods: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10–13 weeks’ gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free β-hCG and PAPP-A were compared with those of the normal control pregnancies. Results: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free β-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free β-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. Conclusions: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10–13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.

Maternal serum human chorionic gonadotrophin and pregnancy‐associated plasma protein A in twin pregnancies in the first trimester

To determine the levels of free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in twin pregnancies in the first trimester. Serum samples were obtained from 67 pregnant women with twin pregnancies and maternal serum free beta-hCG and PAPP-A concentrations were compared with those of 4279 singleton controls between the 8th and 13th weeks of gestation. The geometric means of chromosomally normal twin pregnancies were 1.85 MoM for free beta-hCG and 2.36 MoM for PAPP-A. There were no cases affected by Down syndrome in either group. Twin pregnancies secrete more PAPP-A than expected on the basis of singleton controls whereas free beta-hCG production is not increased. The results of the present study can be used to establish normal reference values when introducing first trimester Down syndrome screening in prenatal care.

Glycosylation of pregnancy-associated plasma protein a (PAPP-A) in normal and trisomic pregnancies: Studies with lectins

Summary Glycosylation of serum PAPP-A in normal pregnancies and in first trimester pregnancies affected by fetal trisomy 21 (T21) was studied using the immobilized lectins Ulex europaeus 1, Lens culinaris, Maackia amurensis and Sambucus nigra . First trimester maternal serum PAPP-A concentration in the T21 group (42 samples) was significantly reduced (46% of the controls). No difference in binding to any lectin, however, was observed between normal and T21 first trimester serum PAPP-A. In normal pregnancy (123 samples), PAPP-A from different gestational weeks was investigated. Its concentration increased between weeks 9 and 25. An increase in the fraction binding to LCL occurred after the first trimester while the MAA-binding fraction was decreasing, indicating a reduction in the content of (α-2,3)-linked sialic acid with unmasking of glucose/mannose residues. Since, in T21, placental PAPP-A production is not reduced (opposite to its serum concentration), our observations could indicate a shift in the dominating source of PAPP-A production from the mother to the placenta after the first trimester.

First trimester maternal serum pregnancy-associated plasma protein A and pregnancy-specific beta 1-glycoprotein in fetal trisomies.

To examine the potential value of maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein (SP1) in the detection of fetal trisomy. Cross-sectional study. The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson Medical College, Philadelphia, USA. Maternal serum PAPP-A and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from 42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy 13, n = 4) and in samples from 210 matched controls. In controls, both maternal serum PAPP-A and SP1 increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SP1 did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in cases with fetal trisomy 21, the deviation was more pronounced at 10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies.

Influence of fetectomy on serum pregnancy-associated plasma protein-A concentrations in the baboon.

In baboons as in humans, the placenta is a source of various peptides, including pregnancy-associated plasma protein-A (PAPP-A). However, our present understanding of the regulation of PAPP-A production is incomplete. We have demonstrated that after fetectomy, the baboon placenta retains steroidogenic capacity and is maintained in utero until delivered spontaneously close to term. We have suggested, therefore, that fetectomy provides a valuable in vivo approach to elucidating the role(s) of the fetus, and of the hormones (e.g., estrogen and progesterone) dependent upon the presence of the fetus, in the regulation of placental steroidogenesis during primate pregnancy. Therefore in the present study we utilized the fetectomy model to evaluate the respective roles of the fetus, estrogen, and progesterone on placental PAPP-A. Estradiol, progesterone, and PAPP-A concentrations were determined by RIA in maternal blood collected under ketamine anesthesia on Days 78-100 (n = 5), Days 102-144 (n = 4), and Days 146-164 (n = 3) of gestation (term = Day 184) in control baboons (Papio anubis) and on Days 110-164 in baboons fetectomized on Day 100 (n = 9). Studies were also conducted in five animals in which placental estrogen was increased by maternal treatment on Days 70-100 with androstenedione and in three animals treated on Days 140-164 with the antiestrogen, ethamoxytriphetol (MER-25; 25 mg/day/kg BW).(ABSTRACT TRUNCATED AT 250 WORDS)