Serum Pregnancy-associated Plasma protein-A Research Articles

Frontonasal facial angle in chromosomally normal fetuses at 11+0 to 13+6 weeks

To establish the normal range of frontonasal angle (FNA) at 11+0 to 13+6 weeks of gestation and the feasibility of FNA measurement, evaluate the correlation of such a parameter with crown-rump length (CRL) and nuchal translucency (NT) and assess the potential of FNA in improving the performance of first trimester sonographic and biochemical screening for trisomy 21. We conducted a prospective study in 400 singleton uncomplicated pregnancies. FNA was obtained during maternal screening for trisomy 21. NT thickness and FNA were measured by 2D ultrasound in a midsagittal plane of the fetal profile. FNA was measured between the line along the upper surface of the frontal bone and the superior edge of the nasal profile until the echogenic tip. Determination of maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) was committed and concomitantly evaluated by blood sample. Patient-specific risk was calculated using Fetal Medicine Foundation software (Astraia Software GMBH, Munich, Germany). Mean FNA increased with CRL from 119.80° at CRL 45 mm to 125.85° at CRL 84 mm. A significant association between the FNA and NT thickness was detected, while no significant association was found between FNA and serum PAPP-A or β-hCG. At 11+0 to 13+6 weeks FNA increases with fetal CRL and NT thickness. Such an increase is not related to serum biochemistry.

Maternal Serum Human Placental Growth Hormone (hPGH) at 11 to 13 Weeks of Gestation in Preeclampsia

Objective. Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11–13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Methods. The maternal serum concentration of hPGH at 11–13 weeks was measured in a case–control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. Results. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. Conclusion. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.

Low maternal PAPP‐A is associated with small‐for‐gestational age newborns and stillbirths

We investigated the association of first trimester low maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels with small-for-gestational age (SGA) newborns and stillbirths (SBs) in a retrospective national population-based register study. The study group comprised 921 women with the lowest 5% PAPP-A levels (< or =0.3 MoM) and the control group comprising 18,615 women with PAPP-A levels >0.3 MoM. In the study group there were 35 (3.8%) and in the control group 213 SGA newborns (1.1%), respectively (OR, 3.41; 95% CI, 2.37-4.91). There were 9 (1.0%) and 51 (0.3%) cases of SBs in the study and control groups, respectively (p < 0.002; OR, 3.59; 95% CI, 1.76-7.32). Low PAPP-A is a risk factor for SGA and SB.

Reference range of birth weight with gestation and first‐trimester prediction of small‐for‐gestation neonates

Firstly, to establish a reference range of birth weight with gestation at delivery; secondly, to identify maternal characteristics that are significantly associated with birth weight; and thirdly, to determine if combinations of maternal characteristics, fetal nuchal translucency thickness (NT), and serum concentrations of free beta-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are significant predictors of small-for-gestational-age (SGA) neonates in the absence of preeclampsia. Maternal characteristics were recorded; fetal NT, maternal serum free β-hCG and PAPP-A were measured at 11 weeks to 13 weeks 6 days in 33,602 women with singleton pregnancies. Regression analysis was used to determine the association of birth weight with gestation at delivery and to establish a reference range with gestation. Logistic regression analysis was used to determine if maternal factors, fetal NT, free β-hCG, and PAPP-A contribute significantly in predicting SGA in the absence of preeclampsia. Birth weight increased with maternal weight and height; it was higher in parous than in nulliparous women and in those with a medical history of pre-pregnancy diabetes mellitus, and it was lower in cigarette smokers, in all racial groups other than in Caucasian women, and in those with a medical history of chronic hypertension and in those who previously delivered SGA neonates. In the SGA group compared with the unaffected group, there were lower median delta NT (0.10 vs 0.12 mm), free β-hCG [0.9 vs 1.0 MoM (multiples of median)], and PAPP-A (0.8 vs 1.0 MoM). The prediction of SGA provided by maternal factors was significantly improved by the addition of fetal NT and PAPP-A (34.0 vs 37.0% at a false-positive rate of 10%). Prediction of the birth of SGA neonates in the absence of preeclampsia can be provided in the first trimester of pregnancy by a combination of maternal characteristics and measurements of parameters used in early screening for aneuploidies.

Effect of temperature on free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A concentration

To examine the effect of the duration of storage of serum and whole blood at different controlled temperatures on the concentrations of both serum free-beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in first-trimester screening for aneuploidies. The concentrations of free beta-hCG and PAPP-A were measured in samples collected from 10 pregnant women and stored as whole blood or serum for 1-8 days at 4, 20 or 40 degrees C. The concentrations measured were adjusted to take day-to-day variations into account and were expressed as a percentage of the values on day 0. In a second study involving 10 pregnant women, free beta-hCG was measured at 10 min and at 2, 4, 8 and 12 h after collection and storage at 30 or 40 degrees C, either as separated serum or as whole blood. The change in the levels of PAPP-A in the separated serum at all three temperatures and in whole blood at 4 degrees C was always less than 10% throughout the 8 days of storage. In whole blood stored at 20 and 40 degrees C, the percentage variation was less than 10% only if the storage period was shorter than 4 days. The concentration of free beta-hCG was not altered by storage of either whole blood or separated serum at 4 degrees C throughout the 8 days of storage. At 20 degrees C, reliable results were obtained only if the maximum storage time was 2 days for separated serum and 1 day for whole blood. At 30 degrees C, reliable results were obtained only if the samples were analyzed within 2 h of collection, and at 40 degrees C the concentrations increased by more than 50% within 2 h and by about 500% after 1 day of storage. In first-trimester screening for aneuploidies, analysis of blood samples should be undertaken within a few minutes of collection, otherwise the samples should be refrigerated at 4 degrees C throughout the interval between collection and analysis.

First‐trimester combined screening for trisomy 21 at 7–14 weeks' gestation

To establish an algorithm for first-trimester combined screening for trisomy 21 with biochemical testing from 7 to 14 weeks' gestation and ultrasound testing at 11-13 weeks. This was a multicenter study of 886 pregnancies with trisomy 21 and 222 475 unaffected pregnancies with measurements of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. Multiple regression modeling of log-transformed marker values was used to produce log multiples of the median (MoM) values for PAPP-A and free β-hCG. The models included terms for the center attended and the machine used for biochemical analysis, gestational age, maternal racial origin, maternal weight, smoking status and method of conception. Bivariate Gaussian distributions were fitted to log MoM PAPP-A and log MoM free β-hCG in trisomy 21 and in unaffected pregnancies. In each case the patient-specific risk for trisomy 21 was estimated by multiplying the individual maternal age-related risk with the likelihood ratio (LR) for fetal nuchal translucency (NT) according to the mixture model and the combined LR for maternal serum free β-hCG and PAPP-A. Estimates of detection rates for trisomy 21 and false-positive rates were calculated for combined screening with measurements of NT at 12 weeks together with measurements of free β-hCG and PAPP-A from 8 to 13 weeks. In trisomy 21 pregnancies the mean log MoM free β-hCG increased linearly with gestation between 7 and 14 weeks, whereas the relation between log MoM PAPP-A and gestation was fitted by a quadratic equation such that the maximum separation between trisomy 21 and unaffected pregnancies occurs at 9-10 weeks. At a false-positive rate of 3% the detection rate of combined screening at 12 weeks was 86% and this increased to 90% by biochemical testing at 9 weeks and ultrasound scanning at 12 weeks. The detection rate increased to 92% by measuring PAPP-A at 9 weeks and free β-hCG at the time of the scan at 12 weeks. The performance of first-trimester biochemical screening for trisomy 21 is best at 9-10 weeks rather than at 7-8 or 11-14 weeks.

Frontomaxillary facial angle at 11 + 0 to 13 + 6 weeks in Chinese population

Objectives. To establish the normal range of frontomaxillary facial (FMF) angle in the first trimester in a Chinese population.Methods. In a prospective study from March 2007 to June 2007, three-dimensional (3D) volumes of the fetal profile in the mid-sagittal plane were recorded from 129 Chinese pregnant women who were screened for trisomy 21 by the combination of fetal nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 13 + 6 weeks. 3D volumes were examined using multiplanar techniques. The FMF angle of each case was measured. The relationship between the measured FMF angle with the other parameter was also examined.Results. The mean FMF angle decreased from 86.8° for a crown-rump length (CRL) of 45 mm to 76.0° for a CRL of 84 mm (FMF angle = 99.49 − 0.28×CRL, r = 0.377, p < 0.0001). There was no significant association between the FMF angle with serum PAPP-A or β-hCG. The mean (SD) difference between FMF angle derived from Chinese formula and that from the published Caucasian equation was 1.47 (0.61) (95% CI 1.37–1.58) (p < 0.0001).Conclusions. In the first trimester, the FMF angle decreases with fetal CRL. There was similarity in the normal value of FMF angle between the Chinese and Caucasian populations.

La pregnancy-associated plasma protein A (PAPP-A)

Summary Pregnancy-associated plasma protein A (PAPP-A), metalloglycoprotein isolated from pregnancy serum, has been also found in different cell systems (vascular cells of smooth muscle, osteoblasts…). Two forms exist: a high-molecular-weight heterotetrameric complex particularly during pregnancy, and an active free form. PAPP-A has been found to proteolytically cleave insulin-like growth factor (IGFBP-4). Automated techniques have been developed particularly for use in prenatal Down's syndrome (DS) screening. Serum PAPP-A concentrations increase during pregnancy, and decreased PAPP-A values have been found to be associated with fetal DS. It is used, in association with free βhCG and measurement of nuchal translucency, in first trimester DS screening. PAPP-A has also been used as a marker of aneuploidies or preeclampsia and predictor of adverse outcome. Moreover, PAPP-A has been described as a marker of instability of atherosclerotic plaque activity and might predict complications in cardiology. But this application requires more sensitive tests in comparison with prenatal diagnosis.

Ductus Venosus in the First Trimester: Contribution to Screening of Chromosomal, Cardiac Defects and Monochorionic Twin Complications

In the first trimester the ductus venosus can be easily identified with color Doppler and a ductus venosus waveform can be obtained by pulsed Doppler. At 11–13 weeks the prevalence of abnormal a-wave in the ductus venosus is inversely related to fetal crown-rump length and maternal serum pregnancy-associated plasma protein-A (PAPP-A), increases with fetal nuchal translucency (NT) thickness and is more common in women of Black racial origin and in fetuses with abnormal karyotype or cardiac defects. Ductus venosus flow provides an independent contribution in the prediction of chromosomal abnormalities when combined with NT and the maternal serum markers of PAPP-A and free β-hCG, increasing the detection rate to 96% at a false-positive rate of 2.6%. Abnormal ductus venosus flow increases the risk of cardiac defects in fetuses with NT above the 95th centile, and it may increase the risk in fetuses with normal NT. In twin pregnancies, abnormal ductus venosus flow is associated with chromosomal abnormalities and cardiac defects. In monochorionic twins, abnormal flow in the ductus venosus in at least 1 of the fetuses increases the risk of developing twin-to-twin transfusion syndrome.

Dépistage combiné de la trisomie 21 au premier trimestre : à propos de cinq ans d’expérience prospective multicentrique

First trimester screening for Down syndrome is yet to become the first intention strategy in France. This screening program at 11-14 weeks of gestation using maternal age, fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A has already been validated for a long time by many international studies. It seems to improve detection rate and decrease false positive rates. We report here five years prospective experience.

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.

First‐trimester umbilical vein blood flow in pregnancies with low serum pregnancy‐associated plasma protein‐A levels: an early predictor of fetal growth restriction

To investigate umbilical vein blood flow (UVBF) during the first trimester in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate umbilical vein (UV) diameter, time-averaged maximum velocity (TAMXV) and UVBF values to the subsequent development of fetal intrauterine growth restriction (IUGR). UVBF assessment was performed at 11 + 0 to 13 + 6 weeks' gestation in 102 singleton pregnancies with PAPP-A concentrations of < 0.3 multiples of the median. UV diameter, UV-TAMXV and UVBF were calculated and analyzed in relation to pregnancy outcome. Pregnancy outcomes were: 51 pregnancies with birth weight ≥ 10(th) centile (Group A), 30 pregnancies with birth weight < 10(th) centile with normal Doppler in the umbilical artery throughout gestation (Group B) and 21 pregnancies with birth weight < 10(th) centile and abnormal umbilical artery Doppler later in gestation (Group C). No differences were found in PAPP-A levels between groups. Group C fetuses exhibited significantly lower values of UV-TAMXV (z-score - 1.99 SDs, t = 8.527, P ≤ 0.0001) and UVBF (z-score - 0.97 SDs, t = 7.420, P ≤ 0.0001) in comparison with normal reference ranges, while no differences were found in Groups A or B. Decreased UV-TAMXV and UVBF at 11 + 0 to 13 + 6 weeks' gestation identify fetuses at risk of developing IUGR among pregnancies with low levels of PAPP-A.

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization

Objective. To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization.Methods. Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system.Results. Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01).Conclusions. Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.

Maternal plasma soluble endoglin at 11–13 weeks' gestation in pre‐eclampsia

To examine the performance of screening for pre-eclampsia (PE) by a combination of maternal factors, soluble endoglin (sEng), pregnancy associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and uterine artery lowest pulsatility index (L-PI) at 11-13 weeks' gestation. Uterine artery L-PI, sEng, PAPP-A and PlGF were measured at 11-13 weeks in 90 singleton pregnancies that subsequently developed PE, including 30 that required delivery before 34 weeks (early PE) and 60 with late PE, and 180 unaffected controls. Screening performance for PE by maternal factors, sEng, PAPP-A, PlGF and uterine artery L-PI and their combinations was determined. In early PE, compared to controls, plasma sEng and uterine L-PI were significantly increased and serum PAPP-A and PlGF were decreased. In late PE, compared to controls, serum PlGF was decreased and uterine L-PI was increased but plasma sEng and serum PAPP-A were not significantly different. In screening for early PE, the detection rate for a 10% false-positive rate was 46.7% for sEng alone and 96.3% for a combination of maternal factors, sEng, PlGF and uterine artery L-PI. Effective screening for early PE can be provided by a combination of maternal factors, sEng, PlGF and uterine artery L-PI at 11-13 weeks' gestation.

Is Serum Pregnancy-Associated Plasma Protein A Really a Potential Marker of Atherosclerotic Carotid Plaque Stability?

Objectives The search for markers predicting risk of plaque rupture in carotid atherosclerosis is still ongoing. Previous findings showed that pregnancy-associated plasma protein-A (PAPP-A) levels correlate with an adverse plaque morphology. However, the role of PAPP-A in plaque destabilisation is still uncertain. Material and methods Patients with carotid artery stenosis involved in the study were asymptomatic ( n = 29) and symptomatic ( n = 37). Carotid plaques were characterised by histology ( n = 33). Immunohistochemistry ( n = 17) was used to determine expression of PAPP-A and CD68 within the plaques. Serum levels of PAPP-A were measured by the enzyme-linked immunosorbent assay (ELISA). Results Circulating PAPP-A levels were significantly higher in patients with unstable versus stable plaques (0.10 ± 0.06 vs. 0.07 ± 0.04 μg ml −1, p = 0.047) and interestingly, in asymptomatic versus symptomatic patients (0.11 ± 0.05 vs. 0.069 ± 0.09 μg ml −1, p = 0.025). These differences remained statistically significant after adjustment for age, gender and degree of stenosis ( p = 0.050). PAPP-A expression in plaques correlated significantly with CD68 positive macrophages, cap-thickness and its serological values ( r = +0.291, p < 0.001, r = −0.639, p < 0.001 and r = 0.618, p < 0.008, respectively). Furthermore, PAPP-A serum values demonstrated a significant positive predictive value of 68.8% for unstable plaques. Conclusion Our present data confirmed the close relationship between expression of PAPP-A and plaque instability and furthermore correlated significantly with cap thickness. However, the question whether PAPP-A is a useful predictive marker of plaque instability remains unresolved.

Correlation between First-Trimester Maternal Serum Markers, Second-Trimester Uterine Artery Doppler Indices and Pregnancy Outcome

Aims: The aim of this study was to assess the correlation between first trimester maternal serum free beta-human chorionic gonadotropin (fBHCG), pregnancy-associated plasma protein A (PAPPA), second-trimester uterine artery (UA) Doppler measurements and adverse pregnancy outcomes. Methods: Serum levels of PAPPA and fBHCG were determined at the first trimester, and patients underwent bilateral UA Doppler assessments at 20–25 weeks of gestation. A serum PAPPA level <0.4 MoM was termed as low and the abnormal Doppler findings were the presence of bilateral notches and RI >0.52 (mean) or unilateral notch and RI >0.66 (90th percentile). Results: Mean PAPPA level was significantly lower in cases with unilateral or bilateral notches (1.09; 0.79 and 0.80 MoM for 0, 1 and 2 notches, p < 0.001). Fifty-two cases (12.8%) had a low PAPPA level; in this group the incidence of abnormal Doppler was significantly higher (34.6 vs. 18.4%, p = 0.011). In the presence of abnormal Doppler in a case with a low serum PAPPA the risk of pregnancy-induced hypertension (OR = 4.56, p = 0.0067), low birth weight (OR = 6.8, p = 0.0002) and the risk of at least one complication (OR = 7.6, p = 0.00001) were significantly high. Conclusion: Combination of first- and second-trimester findings might improve the efficiency of screening for pregnancy complications.

Maternal Serum Placental Protein 13 at Eleven to Thirteen Weeks in Chromosomally Abnormal Pregnancies

Objective: To investigate whether the maternal serum concentration of placental protein 13 (PP13) is altered in chromosomally abnormal pregnancies and to examine the potential value of this placental protein in screening for aneuploidies at 11–13 weeks. Methods: The maternal serum concentration of PP13 at 11–13 weeks was compared in 536 euploid and 134 aneuploid pregnancies (trisomy 21: n = 49; trisomy 18: n = 28; trisomy 13: n = 19; Turner syndrome: n = 28; triploidy: n = 10). Results: Serum PP13, expressed as multiples of the median (MoM) of the euploid group, was not significantly different in trisomy 21 (1.12 MoM) pregnancies, but the levels were decreased in trisomy 18 (0.75 MoM), trisomy 13 (0.65 MoM), Turner syndrome (0.61 MoM) and triploidy (0.19 MoM). In both euploid and aneuploid pregnancies there was a significant association of serum PP13 with both serum pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG; p < 0.0001 for both). Logistic regression analysis demonstrated that the addition of serum PP13 did not improve the prediction of trisomy 13 and 18 provided by a combination of maternal age, nuchal translucency, and serum free β-hCG and PAPP-A. Conclusion: The measurement of maternal serum PP13 at 11–13 weeks does not improve the performance of screening for aneuploidies achieved by current algorithms.

Pregnancy-associated plasma protein-A as a marker for long-term mortality in patients with peripheral atherosclerosis: inconclusive findings from the Linz Peripheral Arterial Disease (LIPAD) study

Pregnancy-associated plasma protein-A (PAPP-A) has been associated with peripheral artery disease (PAD). The aim of this study was to evaluate the utility of PAPP-A as a marker for long-term mortality in patients with atherosclerotic PAD. PAPP-A serum concentrations were measured using an enzymatically amplified two-step sandwich-type immunoassay in 487 consecutive patients admitted to a tertiary care hospital with symptomatic PAD. The main outcome measure was all-cause mortality at 5 years. During follow-up, 114 patients died and 373 survived. The median PAPP-A concentration was higher among decedents compared with survivors (0.96 vs. 0.78 mU/L, p=0.024). The area under the receiver operating characteristic curve for the prediction of 5-year mortality by PAPP-A was 0.57 [95% confidence interval (CI), 0.53-0.61; p=0.026]. Survival probability was not significantly associated with PAPP-A concentrations using Kaplan-Meier curve analysis. However, univariate Cox proportional-hazards regression analysis revealed that PAPP-A was associated with 5-year mortality [risk ratio 1.25; 95% CI, 1.05-1.50; p=0.013 per one standard deviation (SD) increase in log transformed values]. In the multivariate model using a bootstrapping method, the predictive value of PAPP-A remained significant (risk ratio 1.31; 95% CI, 1.01-1.73; p=0.024 per 1 SD increase in log transformed values), even after adjustment for clinical confounders and other biomarkers, such as high-sensitivity C-reactive protein and amino terminal pro-B-type natriuretic peptide. In this study, PAPP-A was an independent predictor of 5-year all-cause mortality in patients with symptomatic PAD. However, based on the weak association between PAPP-A and outcome in our cohort, we consider PAPP-A measurements to not be useful in clinical practice for prognostic purposes in patients with PAD.

Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP‐A at 11–13 weeks

To explore if the addition of pregnancy-associated plasma protein-A (PAPP-A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease. Prospective screening study for early preeclampsia (PE), late PE and gestational hypertension (GH) in women attending their first hospital visit at 11(+0)-13(+6) weeks of gestation. The performance of screening for PE and GH by combinations of maternal factors, uterine artery with the lowest pulsatility index (L-PI), mean arterial pressure (MAP) and serum PAPP-A was determined. There were 8061 unaffected controls, 37 of whom developed early PE, 128 with late PE and 140 with GH. Compared to the controls, in early PE and late PE MAP and uterine artery L-PI were increased and PAPP-A was decreased. In GH PAPP-A was not significantly different from controls. In screening for a combination of maternal factors, uterine artery L-PI, MAP and PAPP-A the detection rate of early PE was 83.8%, at a 5% false-positive rate. In the prediction of late PE and GH there was no significant improvement from the addition of PAPP-A to the combination of maternal factors, MAP and uterine artery L-PI. Measurement of PAPP-A improves the performance of screening for early PE provided by a combination of maternal factors and biophysical tests at 11-13 weeks.

Maternal serum human placental growth hormone at 11 to 13 weeks in trisomy 21 and trisomy 18 pregnancies

To investigate the maternal serum concentration of human placental growth hormone (hPGH) in trisomy 21 and trisomy 18 pregnancies at 11 to 13 weeks of gestation and to examine the possible association between fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). The maternal serum concentration of hPGH at 11 to 13 weeks was measured in a case-control study from 28 pregnancies with fetal trisomy 21, 28 with trisomy 18 and 112 pregnancies with euploid fetuses. The median hPGH multiple of the median (MoM) in trisomy 21 and trisomy 18 pregnancies were compared with euploid pregnancies. Serum hPGH was significantly lower in trisomy 21 (0.93 MoM) and trisomy 18 (0.62 MoM) compared to euploid pregnancies (1.02 MoM). There was a significant association between serum hPGH and PAPP-A in both the euploid (r = 0.258, p = 0.006) and trisomy 21 pregnancies (r = 0.410, p = 0.030) but not in trisomy 18 pregnancies (p = 0.445). In the first trimester, serum hPGH in trisomy 21 and trisomy 18 pregnancies is reduced. This is the opposite of findings in previous studies reporting that in the second trimester, trisomy 21 and 18 pregnancies have increased hPGH.